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Multicenter
Kinds of Multicenter Terms modified by Multicenter Selected AbstractsMulticenter, randomized, double-blind, active comparator and placebo-controlled trial of a corticotropin-releasing factor receptor-1 antagonist in generalized anxiety disorder,DEPRESSION AND ANXIETY, Issue 5 2010Vladimir Coric M.D. Abstract Background: Antagonism of corticotropin-releasing factor (CRF) receptors has been hypothesized as a potential target for the development of novel anxiolytics. This study was designed to determine the safety and efficacy of pexacerfont, a selective CRF-1 receptor antagonist, in the treatment of generalized anxiety disorder (GAD). Method: This was a multicenter, randomized, double-blind, placebo-controlled and active comparator trial. Two hundred and sixty patients were randomly assigned to pexacerfont 100,mg/day (after a 1 week loading dose of 300,mg/day), placebo or escitalopram 20,mg/day in a 2:2:1 ratio. The primary outcome was the mean change from baseline to end point (week 8) in the Hamilton Anxiety Scale total score. Results: Pexacerfont 100,mg/day did not separate from placebo on the primary outcome measure. The half-powered active comparator arm, escitalopram 20,mg/day, demonstrated efficacy with significant separation from placebo at weeks 1, 2, 3, 6, and 8 (P<.02). Response rates for pexacerfont, placebo, and escitalopram were 42, 42, and 53%, respectively. Genetic and psychometric rating scale data was obtained in 175 randomized subjects. There was a significant association between a single nucleotide polymorphism (SNP) of the gene encoding plexin A2 (PLXNA2-2016) with the HAM-A psychic subscale score for the entire cohort at baseline (FDR-adjusted P=.015). Conclusions: Pexacerfont did not demonstrate efficacy compared to placebo for the treatment of GAD. Whether these findings are generalizable to this class of agents remains to be determined. Our preliminary genetic finding of an association between a SNP for the gene encoding plexin A2 and an anxiety phenotype in this study merits further exploration. The trial was registered at clinicaltrials.gov (NCT00481325) before enrollment. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc. [source] A Multicenter, 47-Month Study of Safety and Efficacy of Calcium Hydroxylapatite for Soft Tissue Augmentation of Nasolabial Folds and Other Areas of the FaceDERMATOLOGIC SURGERY, Issue 2007NEIL S. SADICK MD OBJECTIVES Each soft tissue filler product has its own unique profile in terms of adverse events. In this large-scale study, we investigated the safety profile of Radiesse, an injectable calcium hydroxylapatite (CaHA) implant, in treatment of nasolabial folds and other areas of the face. We also investigated the efficacy in a subset of the larger patient group. METHODS After obtaining informed consent from the subjects, researchers injected CaHA at two treatment centers into 113 patients (100 women and 13 men, ranging in age from 26 to 78 years) for a variety of facial aesthetic applications over a period of 47 months. Seventy-five patients had a single injection session; 38 had multiple sessions. Most patients (102) received 1.0 mL of CaHA per session; 12 received 2.0 mL per session. Typically, CaHA was administered with a 27-gauge 0.5- or 1 1/4-in. needle. RESULTS Safety. Of 113 patients, only 7 reported minor adverse events that were short-term and resolved within 1 month: transient ecchymosis (3), nongranulatomous submucosal nodules of the lip (2), and inflammation and edema (2). Efficacy. Efficacy ratings were performed for a subset of patients (n=41). On a scale of 1 to 5 (1=unsatisfactory; 5=excellent), the mean patient evaluation score for look and feel of the implant was 4.6; the mean physician scores for the look and feel of the implant were 4.5 and 4.6, respectively. During the 6-month follow-up visit, patients' mean ratings of the look and feel of the implant were 4.8 and 4.9, respectively. The physician's mean ratings for the look and feel of the implant were 4.5 and 4.9, respectively. CONCLUSIONS In our study, CaHA performed well, with a favorable safety profile, high patient satisfaction (90% of patients reported very good or excellent results), and good durability. We are especially pleased with the low incidence of adverse events coupled with the favorable responses from the patients themselves due to longevity of correction. [source] A Multicenter, Randomized Clinical Study to Evaluate the Effect on Cognitive Function of Topiramate Compared with Valproate as Add-On Therapy to Carbamazepine in Patients with Partial-Onset SeizuresEPILEPSIA, Issue 9 2000A. P. Aldenkamp Summary: Purpose: This study compares the cognitive effects of topiramate (TPM) with those of valproate (VPA) using efficacious doses of each drug when used as adjunctive therapy to carbamazepine (CBZ). A key question of the study is to what extent a more gradual introduction of TPM improves tolerabil-ity and prevents cognitive impairment. Methods: The study is a multicenter, randomized, observer-blinded, parallel-group clinical trial with VPA or TPM given as first-line add-on therapy to steady-state treatment with CBZ. TPM is introduced at 25 mg and increased with weekly 25-mg/d increments to a minimum dosage of 200 mg/d. The target dosage ranges from 200 to 400 mg/d for TPM and is 1800 mg/d for VPA. The study evaluates cognitive function changes from baseline to end point (after 20 weeks of treatment) and during titration (after 8 weeks of treatment). The primary outcome measure is the difference between the treatments (TPM versus VPA) in change from baseline to end point and change from baseline to titration, using a 95% confidence interval approach. Results: For the 10 baseline-to-end point comparisons, one test measuring short-term verbal memory (Rey Auditory Verbal Learning Test) yields a statistically significant difference between the treatments (p = 0.02), showing worsening for TPM and improvement of scores for VPA. The 10 baseline-to-titration comparisons also show one statistically significant difference, again for a test measuring short-term memory (Recognition of Words; p = 0.04), showing a larger change in the negative direction for TPM. None of the mood tests or the test for subjective complaints shows statistically significant differences between the treatments, although more scores are in the negative direction for TPM during titration. Conclusion: Although the pattern of changes in the negative direction seems consistent with clinical information, the differences found between the treatments are small. An important finding of our study is that, when the results are compared with those of other studies, it is clear that gradual introduction of TPM can reduce the extent of cognitive impairment (with a maximum of about 0.6 SD). [source] Differential time effect profiles of amlodipine, as compared to valsartan, revealed by ambulatory blood pressure monitoring, self blood pressure measurements and dose omission protocolFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2004Anca Radauceanu Abstract Amlodipine and valsartan are once-daily antihypertensive agents. To date, no comparison between these agents given as monotherapies was reported. This study was aimed to evaluate the therapeutic coverage and safety of amlodipine and valsartan in mild-to-moderate hypertensive patients. Multicenter, double-blind, randomized, comparative study. After a 4-week placebo wash-out period, 246 outpatients with office diastolic blood pressure 95 , DBP ,110 mmHg and systolic blood pressure (SBP) < 180 mmHg, in addition to a mean daytime SBP and/or DBP > 135/85 mmHg on 24-h ambulatory blood pressure monitoring (ABPM), were randomly allocated to once-daily amlodipine 5,10 mg or valsartan 40,80 mg, for 12 weeks. In a subgroup of patients, 48-h ABPM were performed at the end of the treatment period. Dose omission was simulated by a single-blind placebo dosing. The primary efficacy end-point was the 24-h trough office BP after 12 weeks of active therapy. The reductions in 24-h trough BP were more pronounced in amlodipine compared with valsartan group as well in office [SBP: ,17.8 ± 10.9 vs. ,14.6 ± 11.2, P = 0.025, DBP: ,12.7 ± 7.2 vs. ,10.9 ± 7.8 mmHg, P = 0.06) as in ambulatory BP (SBP/DBP: ,13.0 ± 13.7/,10.8 ± 9.1 vs. ,7.2 ± 19.4/,4.9 ± 13.4 mmHg, P < 0.05). Forty-eight hours after the last active dose, the slope of the morning BP surge (4,9 h) was less steep with amlodipine vs. valsartan [DBP (P < 0.04), SBP (n.s.)]. Ankle edema were more often reported in amlodipine group. These results suggest a superior BP lowering and a longer duration of action with amlodipine compared with valsartan. [source] Meta-analysis of published data on incompletely excised basal cell carcinomas of the ear and nose with introduction of an innovative treatment strategyJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 2 2007Christina Rogalski Summary Background: Auricular/nasal basal cell carcinomas (BCC) often require more surgical procedures than BCCs at other sites. Methods: A meta-analysis of incompletely excised BCCs compares those on the ear and nose to other sites. The combination of photodynamic diagnostics (PDD) and fresh-frozen sections is compared to multi-stage excisions; in each case, the tissue margins were histographically controlled. Results: The relative risk of an incomplete excision of a BCC on the ear/nose is 2.5 fold higher than on the rest of the body. The combination of PDD and micrographic surgery with fresh-frozen sections reduces the length of stay by 42.86 % from median 14 d to 8 d as well as increasing the revenue per patient per day by 41.9 % from 320.61 , to 454.95 , with nearly a comparable rate of recurrences after one year. Conclusions: PDD in combination with single-stage surgery is an equivalent therapy with few side effects and conforming to guidelines. It takes into account both quality assurance and patient preferences. Multicenter, randomized trials seem desirable. [source] Efficacy and Safety of a Once-Yearly Intravenous Zoledronic Acid 5 mg for Fracture Prevention in Elderly Postmenopausal Women with Osteoporosis Aged 75 and OlderJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2010Steven Boonen MD OBJECTIVES: To determine the efficacy of once-yearly intravenous zoledronic acid (ZOL) 5 mg in reducing risk of clinical vertebral, nonvertebral, and any clinical fractures in elderly osteoporotic postmenopausal women. DESIGN: A post hoc subgroup analysis of pooled data from the Health Outcome and Reduced Incidence with Zoledronic Acid One Yearly (HORIZON) Pivotal Fracture Trial and the HORIZON Recurrent Fracture Trial. SETTING: Multicenter, randomized, double-blind, placebo-controlled trials. PARTICIPANTS: Postmenopausal women (aged ,75) with documented osteoporosis (T -score ,,2.5 at femoral neck or ,1 prevalent vertebral or hip fracture) or a recent hip fracture. INTERVENTION: Patients were randomized to receive an intravenous infusion of ZOL 5 mg (n=1,961) or placebo (n=1,926) at baseline and 12 and 24 months. MEASUREMENTS: Primary endpoints were incidence of clinical vertebral and nonvertebral and any clinical fracture after treatment. RESULTS: At 3 years, incidence of any clinical, clinical vertebral, and nonvertebral fracture were significantly lower in the ZOL group than in the placebo group (10.8% vs 16.6%, 1.1% vs 3.7%, and 9.9% vs 13.7%, respectively) (hazard ratio (HR)=0.65, 95% confidence interval (CI)=0.54,0.78, P<.001; HR=0.34, 95% CI=0.21,0.55, P<.001; and HR=0.73, 95% CI=0.60,0.90, P=.002, respectively). The incidence of hip fracture was lower with ZOL but did not reach statistical significance. The incidence rate of postdose adverse events were higher with ZOL, although the rate of serious adverse events and deaths was comparable between the two groups. CONCLUSION: Once-yearly intravenous ZOL 5 mg was associated with a significant reduction in the risk of new clinical fractures (vertebral and nonvertebral) in elderly postmenopausal women with osteroporosis. [source] Multicenter Blinded Analysis of RT-PCR Detection Methods for Paramyxoviruses in Relation to Paget's Disease of Bone,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2007Stuart H Ralston MD Abstract Conflicting results have been reported on the detection of paramyxovirus transcripts in Paget's disease, and a possible explanation is differences in the sensitivity of RT-PCR methods for detecting virus. In a blinded study, we found no evidence to suggest that laboratories that failed to detect viral transcripts had less sensitive RT-PCR assays, and we did not detect measles or distemper transcripts in Paget's samples using the most sensitive assays evaluated. Introduction: There is conflicting evidence on the possible role of persistent paramyxovirus infection in Paget's disease of bone (PDB). Some workers have detected measles virus (MV) or canine distemper virus (CDV) transcripts in cells and tissues from patients with PDB, but others have failed to confirm this finding. A possible explanation might be differences in the sensitivity of RT-PCR methods for detecting virus. Here we performed a blinded comparison of the sensitivity of different RT-PCR,based techniques for MV and CDV detection in different laboratories and used the most sensitive assays to screen for evidence of viral transcripts in bone and blood samples derived from patients with PDB. Materials and Methods: Participating laboratories analyzed samples spiked with known amounts of MV and CDV transcripts and control samples that did not contain viral nucleic acids. All analyses were performed on a blinded basis. Results: The limit of detection for CDV was 1000 viral transcripts in three laboratories (Aberdeen, Belfast, and Liverpool) and 10,000 transcripts in another laboratory (Manchester). The limit of detection for MV was 16 transcripts in one laboratory (NIBSC), 1000 transcripts in two laboratories (Aberdeen and Belfast), and 10,000 transcripts in two laboratories (Liverpool and Manchester). An assay previously used by a U.S.-based group to detect MV transcripts in PDB had a sensitivity of 1000 transcripts. One laboratory (Manchester) detected CDV transcripts in a negative control and in two samples that had been spiked with MV. None of the other laboratories had false-positive results for MV or CDV, and no evidence of viral transcripts was found on analysis of 12 PDB samples using the most sensitive RT-PCR assays for MV and CDV. Conclusions: We found that RT-PCR assays used by different laboratories differed in their sensitivity to detect CDV and MV transcripts but found no evidence to suggest that laboratories that previously failed to detect viral transcripts had less sensitive RT-PCR assays than those that detected viral transcripts. False-positive results were observed with one laboratory, and we failed to detect paramyxovirus transcripts in PDB samples using the most sensitive assays evaluated. Our results show that failure of some laboratories to detect viral transcripts is unlikely to be caused by problems with assay sensitivity and highlight the fact that contamination can be an issue when searching for pathogens by sensitive RT-PCR,based techniques. [source] Multicenter, Prospective, Randomized Safety and Efficacy Study of a New Atrial-Based Managed Ventricular Pacing Mode (MVP) in Dual Chamber ICDsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2005MICHAEL O. SWEENEY M.D. Background: Ventricular desynchronization caused by right ventricular pacing may impair ventricular function and increase risk of heart failure (CHF), atrial fibrillation (AF), and death. Conventional DDD/R mode often results in high cumulative percentage ventricular pacing (Cum%VP). We hypothesized that a new managed ventricular pacing mode (MVP) would safely provide AAI/R pacing with ventricular monitoring and DDD/R during AV block (AVB) and reduce Cum%VP compared to DDD/R. Methods: MVP RAMware was downloaded in 181 patients with Marquis DR ICDs. Patients were initially randomized to either MVP or DDD/R for 1 month, then crossed over to the opposite mode for 1 month. ICD diagnostics were analyzed for cumulative percentage atrial pacing (Cum%AP), Cum%VP, and duration of DDD/R pacing for spontaneous AVB. Results: Baseline characteristics included age 66 ± 12 years, EF 36 ± 14%, and NYHA Class II,III 36%. Baseline PR interval was 190 ± 53 msec and programmed AV intervals (DDD/R) were 216 ± 50 (paced)/189 ± 53 (sensed) msec. Mean Cum%VP was significantly lower in MVP versus DDD/R (4.1 ± 16.3 vs 73.8 ± 32.5, P < 0.0001). The median absolute and relative reductions in Cum%VP during MVP were 85.0 and 99.9, respectively. Mean Cum%AP was not different between MVP versus DDD/R (48.7 ± 38.5 vs 47.3 ± 38.4, P = 0.83). During MVP overall time spent in AAI/R was 89.6% (intrinsic conduction), DDD/R 6.7% (intermittent AVB), and DDI/R 3.7% (AF). No adverse events were attributed to MVP. Conclusions: MVP safely achieves functional atrial pacing by limiting ventricular pacing to periods of intermittent AVB and AF in ICD patients, significantly reducing Cum%VP compared to DDD/R. MVP is a universal pacing mode that adapts to AVB and AF, providing both atrial pacing and ventricular pacing support when needed. [source] Multicenter randomized controlled trial of heat-killed Lactobacillus acidophilus LB in patients with chronic diarrheaJOURNAL OF DIGESTIVE DISEASES, Issue 4 2002Shu Dong XIAO OBJECTIVE: Chronic diarrhea is a common bowel disorder, and disturbance of intestinal microorganisms may play a role in its pathogenesis. The aim of this study was to assess the clinical efficacy of lyophilized heat-killed Lactobacillus acidophilus LB compared with living lactobacilli in the treatment of chronic diarrhea. METHODS: One hundred and thirty-seven patients with chronic diarrhea were randomly allocated to receive either a 4-week course of two capsules of Lacteol Fort twice a day as the Lacteol group (69 patients completed the course) or a 4-week course of five chewable tablets of Lacidophilin three times a day as the Lacidophilin group (64 patients completed the course). The frequency of stools was recorded quantitatively and the semiquantitative parameters such as stool consistency, abdominal pain, distension and feeling of incomplete evacuation were evaluated. RESULTS: At the second and fourth week of the treatment, the mean bowel frequency was significantly lower in the Lacteol group than in the Lacidophilin group (1.88 ± 1.24 vs 2.64 ± 1.12, 1.39 ± 0.92 vs 2.19 ± 1.05, respectively; P < 0.05). At the end of the treatment, the clinical symptoms were markedly improved in the Lacteol group. CONCLUSIONS: Lactobacillus acidophilus LB is more effective than living lactobacilli in the treatment of chronic diarrhea. [source] Low Systemic Absorption and Good Tolerability of Pimecrolimus, Administered as 1% Cream (Elidel®) in Infants with Atopic Dermatitis , A Multicenter, 3-Week, Open-Label StudyPEDIATRIC DERMATOLOGY, Issue 5 2005Doris Staab M.D. Here we evaluate pimecrolimus blood concentrations and tolerability to pimecrolimus cream 1% in 22 infants below 2 years of age with atopic dermatitis (10,92% body surface area affected at baseline). Efficacy was assessed as a secondary objective. Pimecrolimus cream 1% was applied twice daily for 3 weeks. Blood concentrations were low, typically (96% of total 100 concentrations measured) below 2 ng/mL, the majority (71%) remaining below 0.5 ng/mL. The highest concentration observed was 2.26 ng/mL. At steady state, there was no indication of accumulation. Pimecrolimus was well tolerated locally and systemically, with no serious adverse events recorded. Most adverse events recorded (35 in 17/22 patients) were typical of the young pediatric population studied, of mild to moderate severity, and not considered to be study-medication related, with the exception of four local adverse effects limited to the site of cream application. No clinically relevant change was observed in physical examination, vital signs, or laboratory safety parameters. A rapid onset of therapeutic effect was observed within the first four days of treatment. Pimecrolimus cream 1% is well tolerated in infants 3 to 23 months of age treated for 3 weeks, and results in minimal systemic exposure. [source] An Open-Label, Multicenter, Flexible Dose Study to Evaluate the Efficacy and Safety of Viagra® (Sildenafil Citrate) in Korean Men with Erectile Dysfunction and Arterial Hypertension who are Taking Antihypertensive AgentsTHE JOURNAL OF SEXUAL MEDICINE, Issue 10 2008Hyun Jun Park MD ABSTRACT Introduction., Erectile dysfunction (ED) is common among men taking antihypertensive agents to control blood pressure. Aim., We evaluated the efficacy and safety of sildenafil citrate in men with ED taking antihypertensive agents. Methods., A total of 198 male subjects, aged 20 years and older were enrolled. This study was conducted for 10 weeks as an open-label, multicenter and flexible dose trial with a 2-week screening period and an 8-week treatment phase. Main Outcome Measures., Subjects were asked to complete Event Log Worksheets, as well as the International Index of Erectile Function (IIEF) and the Global Efficacy Assessment Questions (GEAQ) questionnaires during the study period. Results., The average age among the 167 subjects who completed the study was 55.8 (31.7 to 77.1). The scores for questions 3 and 4 of IIEF improved from 2.3 and 1.8 at baseline to 3.7 and 3.4 at week 4 and 3.8 and 3.4 at week 8, respectively. There were 86.3% of the patients reported improved erectile function at week 8; 88.3% of the patients reported improved ability to achieve sexual intercourse at week 8. There were no significant differences observed in the responses to questions 3 and 4 of IIEF and GEAQ by the number of antihypertensive agents taken. The adverse events were facial flushing (20.1%), headache (11.7%), palpitation (5.0%), rhinitis (2.8%), URI (2.8%), dizziness (2.2%), dyspnea (2.2%), and nausea (1.7%). Conclusions., Sildenafil citrate is an effective treatment for ED; it is safe and well tolerated by patients with ED taking multiple antihypertensive agents for arterial hypertension. Park HJ, Park NC, Shim HB, Park JK, Lee SW, Park K, Kim SW, Moon KH, Lee DH, and Yoon SJ. An open-label, multicenter, flexible dose study to evaluate the efficacy and safety of Viagra® (sildenafil citrate) in Korean men with erectile dysfunction and arterial hypertension who are taking antihypertensive agents. J Sex Med 2008;5:2405,2413. [source] ORIGINAL RESEARCH,ED PHARMACOTHERAPY: Psychosocial Outcomes and Drug Attributes Affecting Treatment Choice in Men Receiving Sildenafil Citrate and Tadalafil for the Treatment of Erectile Dysfunction: Results of a Multicenter, Randomized, Open-Label, Crossover StudyTHE JOURNAL OF SEXUAL MEDICINE, Issue 4 2006FRCGP, John Dean MBBS ABSTRACT Introduction., Although sildenafil citrate (sildenafil) and tadalafil are efficacious and well-tolerated treatments for erectile dysfunction (ED), preference studies have shown that patients may favor one medication over the other. Aim., To determine whether psychosocial outcomes differed when men with ED received tadalafil compared with sildenafil. Main Outcome Measures., Measures included a treatment preference question, Psychological and Interpersonal Relationship Scales (PAIRS), and Drug Attribute Questionnaire. Methods., Randomized, open-label, crossover study. After a 4-week baseline, men with ED (N = 367; mean age = 54 years; naďve to type 5 phosphodiesterase inhibitor therapy) were randomized: tadalafil for 12 weeks then sildenafil for 12 weeks or vice versa (8-week dose optimization/4-week assessment phases). During dose optimization, patients started with 10 mg tadalafil, or 25 or 50 mg sildenafil and could titrate to their optimal dose (10 or 20 mg tadalafil; 25, 50, or 100 mg sildenafil). Medications were taken as needed. Patients completing both 12-week periods chose which medication to continue during an 8-week extension. Results., Of 291 men completing both treatment periods, 71% (N = 206) chose tadalafil and 29% (N = 85) chose sildenafil (P < 0.001) for the 8-week extension. When taking tadalafil compared with sildenafil men had higher mean endpoint scores on PAIRS Sexual Self-Confidence (tadalafil = 2.91 vs. sildenafil = 2.75; P < 0.001) and Spontaneity (tadalafil = 3.32 vs. sildenafil = 3.17; P < 0.001) Domains and a lower mean endpoint score on Time Concerns Domain (tadalafil = 2.2 vs. sildenafil = 2.59; P < 0.001). The two most frequently chosen drug attributes to explain treatment preference were ability to get an erection long after taking the medication and firmness of erections. Tadalafil and sildenafil were well tolerated with 12 (3.3%) patients discontinuing for an adverse event. Conclusions., As measured with PAIRS, men with ED had higher sexual self-confidence and spontaneity and less time concerns related to sexual encounters when treated with tadalafil compared with sildenafil. These psychosocial outcomes may help explain why more men (71%) preferred tadalafil for the treatment of ED in this clinical trial. Dean J, Hackett GI, Gentile V, Pirozzi-Farina F, Rosen RC, Zhao Y, Warner MR, and Beardsworth A. Psychosocial outcomes and drug attributes affecting treatment choice in men receiving sildenafil citrate and tadalafil for the treatment of erectile dysfunction: Results of a multicenter, randomized, open-label, crossover study. J Sex Med 2006;3:650,661. [source] Conversion from valproic acid onto topiramate in adolescents and adults with epilepsyACTA NEUROLOGICA SCANDINAVICA, Issue 5 2009A. Schreiner Objective,,, To explore efficacy and tolerability outcomes of topiramate (TPM) in patients with epilepsy transitioning from valproic acid (VPA) because of insufficient efficacy and/or tolerability onto TPM. Methods,,, Multicenter, open label, single arm, non-interventional study examining patients (,12 years) with epilepsy, transitioning onto TPM from baseline mono-or combination therapy with VPA. TPM was added onto the existing antiepileptic drug (AED) treatment and started at a dose of 25 mg once daily. The dose was titrated up with 25 mg/day increments, once every 1,2 weeks, until a final dose between 50,200 mg/day was reached. Based on clinical judgment, the treating physician decided whether or not and when the existing AED treatment especially with VPA could be withdrawn. Documented were type and frequency of seizures, TPM dose, quality of life (QOLIE-10 questionnaire), subjective perception of improvement, and adverse events (AE). Results,,, One hundered and forty-seven patients (59% women, mean age 41 years) switched from baseline VPA treatment onto TPM because of insufficient efficacy (61%) and/or poor tolerability (81%). Average duration of follow-up was 20.3 weeks with an overall discontinuation rate of 16.3% of patients, mainly because of AE (in 8.2% of 147 patients). At study endpoint, the intended shift to TPM monotherapy was achieved in 70% of patients at a median dose of 150 mg/day. A seizure reduction of ,50% was achieved in 75% of patients in the last scheduled period (week 8,20), and 51% of patients entering that period remained seizure-free. Quality of life improved significantly as compared with baseline for all domains of QOLIE-10 (P < 0.001). Most frequent AEs were weight decrease (4.8%), paraesthesia and fatigue (4.1% each), speech disorder and headaches (2.7% each). Conclusions,,, In patients with epilepsy not satisfactorily treated with VPA, conversion to TPM was associated with improved seizure control as well as improvement in several aspects of quality of life. [source] Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosisCANCER, Issue 12 2006Johan Maertens MD Abstract BACKGROUND. Caspofungin inhibits synthesis of ,-1,3-glucan, an essential component of the Aspergillus cell wall. This echinocandin has demonstrated efficacy (45% success) as salvage monotherapy of invasive aspergillosis (IA). Interest remains as to whether caspofungin, in combination with other antifungal classes, can improve the efficacy against IA. METHODS. The study involved 53 adults with documented IA who were refractory to or intolerant of standard antifungal therapy and received caspofungin and 1 other mold-active antifungal agent (at the investigator's discretion). Efficacy was assessed by signs, symptoms, and radiographs at the end of combination therapy and Day 84 after combination therapy initiation. Favorable (complete or partial) responses required significant clinical and radiographic improvement. Diagnoses and outcomes were assessed by an independent expert. RESULTS. Among the 53 patients enrolled the most common underlying diseases were acute leukemia (53%), lymphoma (11%), and chronic leukemia (6%). Pulmonary aspergillosis (81%) was the most common site, and most patients (87%) were refractory to prior therapy. Success at the end of combination therapy and Day 84 was 55% (29/53) and 49% (25/51), respectively. Fifty-seven percent of patients with neutropenia and 54% who received an allogeneic hematopoietic stem cell transplant responded favorably. Survival at Day 84 was 55%. Combination therapy, dosed on average for 31.3 days, was well tolerated. Two (4%) serious drug-related adverse events, both attributed to voriconazole, occurred. None of the patients discontinued caspofungin due to toxicity. CONCLUSIONS. Caspofungin in combination with a triazole or polyene was an effective alternative as salvage therapy for patients with recalcitrant Aspergillus infections. Cancer 2006. © 2006 American Cancer Society. [source] A Multicenter, Placebo-Controlled, Double-Blind, Randomized Study of Efficacy and Safety of Ocinaplon (DOV 273,547) in Generalized Anxiety DisorderCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 2 2010Pál Czobor Preclinical studies demonstrated that ocinaplon, a positive allosteric modulator of GABAA receptors, possesses anxiolytic-like actions at doses devoid of the side effects typically associated with benzodiazepines. The aim of this study was to evaluate the effects of ocinaplon in a multicenter, double-blind proof-of-concept trial of male and female outpatients who met DSM-IV criteria for GAD with no coexisting depression, and had a baseline score of ,20 on the Hamilton Scale for Anxiety (HAM-A). Patients with <20% reduction in HAM-A to placebo in a single-blind 7-day run-in period were randomly assigned to treatment with ocinaplon 90 mg t.i.d. (n = 31) or placebo for 28 days (n = 29). Ocinaplon was more effective than placebo in reducing HAM-A scores (P= 0.009). Patients assigned to ocinaplon exhibited a mean improvement of 14.2 points (SE = 2.6) on the total score of the HAM-A scale at the conclusion of the trial, while patients assigned to placebo obtained a mean improvement of 6.3 points (SE = 2.0). A significant (P= 0.023) difference in improvement between ocinaplon and placebo was observed beginning at and continuing from 1-week after the initiation of dosing. The proportion of patients with treatment-emergent adverse events (TEAE) was not statistically significant between ocinaplon and placebo. One serious adverse event (SAE) occurred in the ocinaplon group that was considered possibly related to study medication (icterus following transaminase elevations). The patient had preexisting medical conditions that may have contributed to this SAE. A full recovery was observed with no residual effects. The overall safety profile revealed no patterns of TEAEs, including those effects typically associated with other anxiolytic and/or benzodiazepine compounds, such as sedation. Ocinaplon appears to be a well-tolerated and effective treatment for GAD. It produces a rapid onset of anxiolytic action absent the side effects (e.g., dizziness, sedation) typically reported following anxiolytic doses of benzodiazepines. [source] Clinical and Hemodynamic Effects of Nesiritide (B-Type Natriuretic Peptide) in Patients With Decompensated Heart Failure Receiving , BlockersCONGESTIVE HEART FAILURE, Issue 2 2005William T. Abraham MD The use of , blockers in congestive heart failure presents a therapeutic challenge for patients with acute episodes of decompensation. Such patients may be less responsive to positive inotropic agents, whereas the beneficial effects of nesiritide, which are not dependent on the ,-adrenergic receptor signal-transduction pathway, may be preserved. This analysis of the Vasodilation in the Management of Acute CHF trial evaluated the safety and efficacy of nesiritide in decompensated congestive heart failure patients receiving , blockers. The Vasodilation in the Management of Acute CHF trial was a multicenter, randomized, controlled evaluation of nesiritide in 489 hospitalized patients with decompensated congestive heart failure. One hundred twenty-three patients were on chronic ,-blocker therapy at enrollment (31 randomized to placebo, 50 to nesiritide, and 42 to nitroglycerin). Primary end points included pulmonary capillary wedge pressure and dyspnea evaluation at 3 hours. Patients receiving nesiritide, but not IV nitroglycerin, had significantly reduced pulmonary capillary wedge pressure vs. placebo at 3 hours regardless of ,-blocker use. The use of , blockers did not alter the beneficial effects of nesiritide on systemic blood pressure, heart rate, or dyspnea evaluation. In nesiritide-treated subjects, safety profiles were similar regardless of ,-blocker use. Thus, the clinical and hemodynamic benefits and safety of nesiritide are preserved in decompensated congestive heart failure patients receiving chronic , blockade. [source] Multicenter, randomized, double-blind, active comparator and placebo-controlled trial of a corticotropin-releasing factor receptor-1 antagonist in generalized anxiety disorder,DEPRESSION AND ANXIETY, Issue 5 2010Vladimir Coric M.D. Abstract Background: Antagonism of corticotropin-releasing factor (CRF) receptors has been hypothesized as a potential target for the development of novel anxiolytics. This study was designed to determine the safety and efficacy of pexacerfont, a selective CRF-1 receptor antagonist, in the treatment of generalized anxiety disorder (GAD). Method: This was a multicenter, randomized, double-blind, placebo-controlled and active comparator trial. Two hundred and sixty patients were randomly assigned to pexacerfont 100,mg/day (after a 1 week loading dose of 300,mg/day), placebo or escitalopram 20,mg/day in a 2:2:1 ratio. The primary outcome was the mean change from baseline to end point (week 8) in the Hamilton Anxiety Scale total score. Results: Pexacerfont 100,mg/day did not separate from placebo on the primary outcome measure. The half-powered active comparator arm, escitalopram 20,mg/day, demonstrated efficacy with significant separation from placebo at weeks 1, 2, 3, 6, and 8 (P<.02). Response rates for pexacerfont, placebo, and escitalopram were 42, 42, and 53%, respectively. Genetic and psychometric rating scale data was obtained in 175 randomized subjects. There was a significant association between a single nucleotide polymorphism (SNP) of the gene encoding plexin A2 (PLXNA2-2016) with the HAM-A psychic subscale score for the entire cohort at baseline (FDR-adjusted P=.015). Conclusions: Pexacerfont did not demonstrate efficacy compared to placebo for the treatment of GAD. Whether these findings are generalizable to this class of agents remains to be determined. Our preliminary genetic finding of an association between a SNP for the gene encoding plexin A2 and an anxiety phenotype in this study merits further exploration. The trial was registered at clinicaltrials.gov (NCT00481325) before enrollment. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc. [source] Persistence and Improvement of Nasolabial Fold Correction with Nonanimal-Stabilized Hyaluronic Acid 100,000 Gel Particles/mL Filler on Two Retreatment Schedules: Results up to 18 Months on Two Retreatment SchedulesDERMATOLOGIC SURGERY, Issue 2008RHODA S. NARINS MD BACKGROUND Nonanimal-stabilized hyaluronic acid (NASHA) fillers are frequently used for facial soft tissue augmentation. Their long-term efficacy and the effects of different retreatment schedules are not well established. OBJECTIVE This is an 18-month interim analysis of a 30-month study to evaluate the efficacy and persistence of NASHA 100,000 gel particles/mL filler with two different retreatment schedules. METHODS This multicenter, randomized, evaluator-blinded study enrolled 75 patients with moderate to severe nasolabial folds. Patients were randomized to retreatment of one nasolabial fold at 4.5 months and the contralateral fold at 9 months after correction of both folds at the initial visit. RESULTS Wrinkle Severity Rating Scale scores improved significantly (p<.001) from baseline, with mean improvements ranging from 1.1 to 1.7 grades. Almost all patients (97%) responded satisfactorily, and the efficacy of the retreatment schedules did not differ significantly. Adverse events, primarily swelling and bruising, occurred in 33% of patients; none were serious. CONCLUSION The improvements seen after initial treatment with NASHA 100,000 gel particles/mL filler persisted for up to 18 months with one retreatment. The response was equivalent for retreatment at 4.5 and 9 months. [source] Comparing botulinum toxin A with casting for treatment of dynamic equinus in children with cerebral palsyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2005Jeffrey D Ackman MD The purpose of this study was to compare the cumulative efficacy (three treatment sessions) of botulinum toxin A (BTX-A) alone, casting alone, and the combination of BTX-A and casting in the management of dynamic equinus in ambulatory children with spastic cerebral palsy (CP). Thirty-nine children with spastic CP (mean age 5y 10mo, range 3 to 9y) were enrolled in the study. A multicenter, randomized, double blind, placebo-controlled prospective study was used. Children were randomly assigned to one of three treatment groups: BTX-A only (B), placebo injection plus casting (C), or BTX-A plus casting (B+C). The dosage for the BTX-A injections was 4U/kg per extremity. Assessments were performed at baseline, 3,6,7.5, and 12 months with a total of three treatments administered after the evaluations at baseline, 3, and 6 months. Primary outcome measures were ankle kinematics, velocity, and stride length. Secondary outcome measures were ankle spasticity, strength, range of motion, and ankle kinetics. Group B made no significant change in any variable at any time. Groups C and B+C demonstrated significant improvements in ankle kinematics, spasticity, passive range of motion, and dorsiflexor strength. Results of this 1-year study indicate that BTX-A alone provided no improvement in the parameters measured in this study, while casting and BTX-A/casting were effective in the short- and long-term management of dynamic equinus in children with spastic CP. [source] Enhanced Left Ventricular Endocardial Border Delineation with an Intravenous Injection of SonoVue, a New Echocardiography Contrast Agent:ECHOCARDIOGRAPHY, Issue 8 2000A European Multicenter Study The safety and efficacy of SonoVue (also referred to as BR1), a new contrast agent for delineating endocardial border of the left ventricle after intravenous administration, was assessed. Two hundred and eighteen patients with suspected coronary artery disease undergoing fundamental echocardiography for the assessment of left ventricle were enrolled in a prospective multicenter, single blind, cross-over study with random sequence allocation of four different doses of SonoVue. Endocardial border definition in the apical and parasternal views was scored as O = not visible, 1 = barely visible, and 2 = well visualized before and after contrast enhancement. Analysis was performed by two pairs of off-site observers. Safety of SonoVue was also assessed. Results of our study indicated that the mean improvements in the endocardial border visualization score were as follows: 3.1 ± 7.8 (95% CI, 2.5 and 3.7) for 0.5 ml, 3.4 ± 8.0 (95% CI, 2.8 and 4.0) for 1 ml, 3.4 ± 7.9 (95% CI, 2.8 and 4.0) for 2 ml, and 3.7 ± 8.0 (95% CI, 3.1 and 4.3) for 4 ml (P < 0.05 for all doses from baseline). Changes from baseline in endocardial visualization scores were also seen in the apical views (P < 0.05) and they were dose-dependent (P < 0.001). Similar enhancements of endocardial visualization scores were observed in the apical views in patients with suboptimal baseline echocardiographic images. Diagnostic confidence for assigning a score and image quality also were significantly better following contrast enhancement. No significant changes in the laboratory parameters and vital signs were noted following contrast enhancement, and the side effects were minimal. It was concluded that SonoVue is safe and effective in delineating endocardial border, including in patients with suboptimal baseline images. [source] Intravenous lacosamide as short-term replacement for oral lacosamide in partial-onset seizuresEPILEPSIA, Issue 6 2010Gregory Krauss Summary Purpose:, Lacosamide is a new antiepileptic drug effective for adjunctive treatment of partial-onset seizures. We evaluated the safety and tolerability of an intravenous (i.v.) formulation of lacosamide (200,800 mg/day) infused over 10, 15, and 30 min as short-term replacement for oral lacosamide in patients with partial-onset seizures. Methods:, This multicenter, open-label, inpatient trial enrolled 160 patients from ongoing open-label, long-term trials who were taking stable doses of oral lacosamide and up to three concomitant antiepileptic drugs (AEDs). Serial cohorts of patients were converted from oral lacosamide treatment to the same intravenous doses infused over progressively shorter infusion durations: 30, 15, and 10 min for 2,5 days. A data monitoring committee (DMC) reviewed safety data for each cohort. The safety of intravenous lacosamide was assessed from adverse events (AEs), laboratory variables, electrocardiography findings, and physical/neurologic examinations. Results:, A total of 160 patients received lacosamide 200,800 mg/day, i.v., for 2,5 days, of which 69% received 400,800 mg/day doses. The most common AEs (reported by ,10% of patients) were headache, dizziness, and somnolence. There was no increase in frequency or severity of AEs with shorter durations of infusion or increased days of exposure. AEs were similar, but more frequent, with higher doses (,400 mg/day). Injection-site events were rare and did not appear to be linked to infusion doses or rates. Lacosamide plasma concentrations were linearly related to dose across the cohorts. Discussion:, This comprehensive evaluation supports the safety of an intravenous lacosamide infusion duration as short as 15 min for short-term (2,5 days) replacement for patients temporarily unable to take oral lacosamide. [source] Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a randomized controlled trialEPILEPSIA, Issue 3 2009Péter Halász Summary Purpose:, To evaluate the efficacy and safety of lacosamide (200 and 400 mg/day) when added to one to three concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. Methods:, This multicenter, double-blind, placebo-controlled trial randomized patients (age 16,70 years) with partial-onset seizures with or without secondary generalization to placebo, lacosamide 200, or lacosamide 400 mg/day. The trial consisted of an 8-week baseline, a 4-week titration, and a 12-week maintenance period. Results:, Four hundred eighty-five patients were randomized and received trial medication. Among these, 87% were taking two or more concomitant AEDs. Median percent reduction in seizure frequency per 28 days from baseline to maintenance period (intent-to-treat, ITT) was 20.5% for placebo, 35.3% for lacosamide 200 mg/day (p = 0.02), and 36.4% for 400 mg/day (p = 0.03). In the per protocol population, the reductions were 35.3% for lacosamide 200 mg/day (p = 0.04) and 44.9% for 400 mg/day (p = 0.01) compared to placebo (25.4%). The 50% responder rate for lacosamide 400 mg/day (40.5%) was significant (p = 0.01) over placebo (25.8%), but was not for 200 mg/day (35.0%). In the per protocol population, the 50% responder rate for lacosamide 400 mg/day (46.3%) was significant (p < 0.01) compared with the placebo responder rate (27.5%). Dose-related adverse events (AEs) included dizziness, nausea, and vomiting. Clinically relevant changes in the mean plasma concentrations of commonly used AEDs were not observed. Discussion:, Results of this trial demonstrated the efficacy and tolerability of adjunctive lacosamide 200 and 400 mg/day and support that lacosamide may be an advantageous option for the treatment of partial-onset seizures in patients with epilepsy. [source] Valproate-induced thrombocytopenia: a prospective monotherapy studyEPILEPSIA, Issue 3 2008Wassim Nasreddine Summary Purpose: The frequency of valproate (VPA)-induced thrombocytopenia varied widely in previous studies, due to methodological differences. Our objective was to evaluate the relationship between trough VPA plasma levels and platelet counts and assess risk factors for the development of thrombocytopenia. Methods: Patients with refractory partial epilepsy were enrolled in this double-blind, multicenter, concentration,response trial that evaluated the efficacy and safety of high versus low trough plasma VPA concentrations following administration of divalproex sodium as monotherapy. Trough VPA concentrations and concomitant platelet counts were drawn at baseline and intermittently throughout the 24-week trial. Bivariate correlations and multivariate stepwise regression analysis were performed between platelet counts and multiple variables. A logistic regression analysis was done to determine the probability of developing thrombocytopenia at various VPA levels. Results: A total of 851 VPA levels and concomitant platelet counts were analyzed in 265 patients. Of these, 17.7% of patients experienced at least one episode of thrombocytopenia (platelet count , 100,000/,l) after exposure to divalproex sodium. A significant negative correlation was found between VPA levels and platelet counts. Women were significantly more likely to develop thrombocytopenia. The probability of developing thrombocytopenia substantially increased at trough VPA levels above 100 ,g/ml in women and above 130 ,g/ml in men. Discussion: Our data strongly support a causal relationship between rising plasma VPA levels and reduced platelet counts, with additional risk factors including female gender and lower baseline platelet counts. [source] Efficacy and Safety of Oral Lacosamide as Adjunctive Therapy in Adults with Partial-Onset SeizuresEPILEPSIA, Issue 7 2007Elinor Ben-Menachem Summary:,Purpose: To evaluate the efficacy and safety of lacosamide when added to 1 or 2 antiepileptic drugs (AEDs) in adults with uncontrolled partial-onset seizures, and assess plasma concentrations of concomitant AEDs to determine any potential for drug interactions. Methods: During this multicenter, double-blind, placebo-controlled trial, patients were randomized to placebo or lacosamide 200, 400, or 600 mg/day after an 8-week baseline period. Lacosamide was titrated in weekly increments of 100 mg/day over 6 weeks and maintained for 12 weeks. Results were analyzed on an intention-to-treat basis. Results: Four hundred eighteen patients were randomized and received trial medication; 312 completed the trial. The median percent reduction in seizure frequency per 28 days was 10%, 26%, 39%, and 40% in the placebo, lacosamide 200, 400, and 600 mg/day treatment groups, respectively. The median percent reduction in seizure frequency over placebo was significant for lacosamide 400 mg/day (p = 0.0023) and 600 mg/day (p = 0.0084). The 50% responder rates were 22%, 33%, 41%, and 38% for placebo, lacosamide 200, 400, and 600 mg/day, respectively. The 50% responder rate over placebo was significant for lacosamide 400 mg/day (p = 0.0038) and 600 mg/day (p = 0.0141). Adverse events that appeared dose-related included dizziness, nausea, fatigue, ataxia, vision abnormal, diplopia, and nystagmus. Lacosamide did not affect mean plasma concentrations of concomitantly administered AEDs. Conclusions: In this trial, adjunctive lacosamide significantly reduced seizure frequency in patients with uncontrolled partial-onset seizures. Along with favorable pharmacokinetic and tolerability profiles, these results support further development of lacosamide as an AED. [source] Eslicarbazepine Acetate: A Double-blind, Add-on, Placebo-controlled Exploratory Trial in Adult Patients with Partial-onset SeizuresEPILEPSIA, Issue 3 2007Christian Elger Summary:,Objective: To explore the efficacy and safety of eslicarbazepine acetate (BIA 2-093), a new antiepileptic drug, as adjunctive therapy in adult patients with partial epilepsy. Methods: A multicenter, double-blind, randomized, placebo-controlled study was conducted in 143 refractory patients aged 18,65 years with ,4 partial-onset seizures/month. The study consisted of a 12-week treatment period followed by a 1-week tapering off. Patients were randomly assigned to one of three groups: treatment with eslicarbazepine acetate once daily (QD, n = 50), twice daily (BID, n = 46), or placebo (PL, n = 47). The daily dose was titrated from 400 mg to 800 mg and to 1,200 mg at 4-week intervals. The proportion of responders (patients with a ,50% seizure reduction) was the primary end point. Results: The percentage of responders versus baseline showed a statistically significant difference between QD and PL groups (54% vs. 28%; 90% CI =,,, ,14; p = 0.008). The difference between the BID (41%) and PL did not reach statistical significance (90% CI =,,, ,1; p = 0.12). A significantly higher proportion of responders in weeks 5,8 was found in the QD group than in the BID group (58% vs. 33%, respectively, p = 0.022). At the end of the 12-week treatment, the number of seizure-free patients in the QD and BID groups was 24%, which was significantly different from the PL group. The incidence of adverse events was similar between the treatment groups and no drug-related serious adverse events occurred. Conclusion: Eslicarbazepine acetate was efficacious and well tolerated as an adjunctive therapy of refractory epileptic patients. [source] Combined Ketogenic Diet and Vagus Nerve Stimulation: Rational Polytherapy?EPILEPSIA, Issue 1 2007Eric H. Kossoff Summary:,Objective: The concept of "rational polypharmacy" has been associated with anticonvulsant management for decades, but the term has not been applied to nonpharmacologic therapies. Methods: We conducted a multicenter, retrospective study of children who received concurrent diet (ketogenic or modified Atkins) and vagus nerve stimulation (VNS) treatment for medically intractable epilepsy. Results: Thirty children in total from six epilepsy centers were treated over a 6-yr period. The median age at the initiation of combination therapy was 10 yr (range, 4,24 yr). Sixteen (53%) received dietary therapy followed by VNS; no differences were noted between centers. After 3 months, 21 (70%) had seizure reduced by >50% over the previous single nonpharmacologic treatment, of whom 13 (62%) had improvement within the first month. A 5-min VNS off-time correlated with >90% seizure reduction (p = 0.02). The median duration of nonpharmacologic polytherapy was 12 months (range, 0.5,96 months); 17 (57%) remain on dual therapy at this time. No side effects were noted. Most patients who discontinued combination therapy did so because of a lack of efficacy rather than restrictiveness. Conclusions: In this small group, the combined use of diet and VNS appeared synergistic and yielded rapid benefits. It may be more effective with longer VNS off-times. Further prospective studies of this combination in refractory pediatric epilepsy are needed to help guide optimal use. [source] Time Course of Adverse Events in Patients with Localization-related Epilepsy Receiving Topiramate Added to CarbamazepineEPILEPSIA, Issue 5 2005Jerzy Majkowski Summary:,Purpose: To explore the time course of treatment-emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy. Methods: Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double-blind, placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment-resistant partial-onset seizures. The daily incidence and mean duration of the most common (,5% incidence) AEs were calculated for patients completing the 12-week study. Results: The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits. Conclusions: This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy. [source] A Multicenter, Randomized Clinical Study to Evaluate the Effect on Cognitive Function of Topiramate Compared with Valproate as Add-On Therapy to Carbamazepine in Patients with Partial-Onset SeizuresEPILEPSIA, Issue 9 2000A. P. Aldenkamp Summary: Purpose: This study compares the cognitive effects of topiramate (TPM) with those of valproate (VPA) using efficacious doses of each drug when used as adjunctive therapy to carbamazepine (CBZ). A key question of the study is to what extent a more gradual introduction of TPM improves tolerabil-ity and prevents cognitive impairment. Methods: The study is a multicenter, randomized, observer-blinded, parallel-group clinical trial with VPA or TPM given as first-line add-on therapy to steady-state treatment with CBZ. TPM is introduced at 25 mg and increased with weekly 25-mg/d increments to a minimum dosage of 200 mg/d. The target dosage ranges from 200 to 400 mg/d for TPM and is 1800 mg/d for VPA. The study evaluates cognitive function changes from baseline to end point (after 20 weeks of treatment) and during titration (after 8 weeks of treatment). The primary outcome measure is the difference between the treatments (TPM versus VPA) in change from baseline to end point and change from baseline to titration, using a 95% confidence interval approach. Results: For the 10 baseline-to-end point comparisons, one test measuring short-term verbal memory (Rey Auditory Verbal Learning Test) yields a statistically significant difference between the treatments (p = 0.02), showing worsening for TPM and improvement of scores for VPA. The 10 baseline-to-titration comparisons also show one statistically significant difference, again for a test measuring short-term memory (Recognition of Words; p = 0.04), showing a larger change in the negative direction for TPM. None of the mood tests or the test for subjective complaints shows statistically significant differences between the treatments, although more scores are in the negative direction for TPM during titration. Conclusion: Although the pattern of changes in the negative direction seems consistent with clinical information, the differences found between the treatments are small. An important finding of our study is that, when the results are compared with those of other studies, it is clear that gradual introduction of TPM can reduce the extent of cognitive impairment (with a maximum of about 0.6 SD). [source] A multicenter, open, non-comparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, and G-CSF as induction therapy in refractory acute myeloid leukemia , a report of the Polish Adult Leukemia Group (PALG)EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2003A. Wrzesie Abstract: Objectives: To evaluate the efficacy and toxicity of cladribine (2-chlorodeoxyadenosine, 2-CdA), cytarabine (Ara-C), and granulocyte-colony stimulating factor (G-CSF) (CLAG) regimen in refractory acute myeloid leukemia (AML) in the multicenter phase II study. Methods: The induction chemotherapy consisted of 2-CdA 5 mg/m2, Ara-C2 g/m2, and G-CSF. In the case of partial remission (PR), a second CLAG was administered. Patients in complete remission (CR) received two consolidation courses based on HD Ara-C, mitoxantrone or idarubicine, with or without 2-CdA. Results: Fifty-eight patients from 11 centers were registered; 50 primary resistant and eight early relapsed (CR1 < 6 months). CR was achieved in 29 (50%) patients, 19 (33%) were refractory, and 10 (17%) died early. Forty of 50 primary resistant patients received daunorubicin (DNR) and Ara-C as the first-line induction therapy (DA-7), 10 received additional 2-CdA (DAC-7). The CR rates after CLAG were 58% and 10%, respectively in each group (P = 0.015). Five of six patients with myelodysplastic syndrome (MDS)/AML achieved CR. Hematologic toxicity was the most prominent toxicity of this regimen. The overall survival (OS, 1 yr) for the 58 patients as a whole, and the 29 patients in CR were 42% and 65%, respectively. Disease-free survival (DFS, 1 yr) was 29%. Only first-line induction treatment with DA-7 significantly influenced the probability of CR after CLAG. None of the analyzed factors significantly influenced DFS and OS. Conclusion: CLAG regimen has significant anti-leukemic activity and an acceptable toxicity in refractory AML. The addition of 2-CdA to the first-line induction treatment may worsen the results of salvage with CLAG. The high CR rate in patients with MDS preceding AML deserves further observation. [source] Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: A multicenter, randomized, double-blind, phase III study in North America,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2003Dan J. Castro MD Abstract Background. The objective was to evaluate the efficacy and safety of a novel intratumoral cisplatin/epinephrine injectable gel (CDDP/epi gel) for local control and palliation of tumor-related symptoms in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Patients and Methods. Eighty-seven patients were randomly assigned to either CDDP/epi or placebo gel in this phase III, double-blind study. Tumors were ,20 cm3; most recurrences (88%) were in a previously irradiated field. The most symptomatic or threatening tumor was designated as the target tumor. Dose: 0.25 mL CDDP/epi gel/cm3 tumor volume. Treatments: ,6 weekly intratumoral injections in an 8-week period. Primary outcomes: target tumor response and symptom relief. Results. During the blinded phase, 34% (21 of 62) of patients achieved an objective response (CR or PR) in the target tumor treated with CDDP/epi gel vs 0% (0 of 24) treated with placebo gel (p < .001). Responses occurred within a median of four treatments (range, 2,6) and were durable (median, 95 days; range, 34,168+ days). More patients treated with CDDP/epi gel achieved palliative benefit than did those treated with placebo gel (37% vs 12%, p = .036). Most frequent side effects were local pain and local cutaneous reactions, which resolved over 3,12 weeks. Renal and hematologic toxicities were rare. Conclusions. This phase III trial showed that CDDP/epi gel significantly reduces tumor burden, palliates tumor-related symptoms, and is an effective local treatment for recurrent tumors. © 2003 Wiley Periodicals, Inc. Head Neck 25: 717,731, 2003 [source] | ||||||||||||||||||||||||||||||||||||||||