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Intent-to-treat Analysis (intent-to-treat + analysis)
Selected AbstractsA Placebo-Controlled Randomized Clinical Trial of Naltrexone in the Context of Different Levels of Psychosocial InterventionALCOHOLISM, Issue 7 2008David W. Oslin Background:, Naltrexone is approved for the treatment of alcohol dependence when used in conjunction with a psychosocial intervention. This study was undertaken to examine the impact of 3 types of psychosocial treatment combined with either naltrexone or placebo treatment on alcohol dependency over 24 weeks of treatment: (1) Cognitive-Behavioral Therapy (CBT) + medication clinic, (2) BRENDA (an intervention promoting pharmacotherapy) + medication clinic, and (3) a medication clinic model with limited therapeutic content. Methods:, Two hundred and forty alcohol-dependent subjects were enrolled in a 24-week double-blind placebo-controlled study of naltrexone (100 mg/d). Subjects were also randomly assigned to 1 of 3 psychosocial interventions. All patients were assessed for alcohol use, medication adherence, and adverse events at regularly scheduled research visits. Results:, There was a modest main treatment effect for the psychosocial condition favoring those subjects randomized to CBT. Intent-to-treat analyses suggested that there was no overall efficacy of naltrexone and no medication by psychosocial intervention interaction. There was a relatively low level of medication adherence (50% adhered) across conditions, and this was associated with poor outcome. Conclusions:, Results from this 24-week treatment study demonstrate the importance of the psychosocial component in the treatment of alcohol dependence. Moreover, results demonstrate a substantial association between medication adherence and treatment outcomes. The findings suggest that further research is needed to determine the appropriate use of pharmacotherapy in maximizing treatment response. [source] Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: Results of a two-year, randomized, double-blind, placebo-controlled trialARTHRITIS & RHEUMATISM, Issue 5 2002James R. O'Dell Objective To compare the efficacy of combination therapy with methotrexate (MTX) and hydroxychloroquine (HCQ), MTX and sulfasalazine (SSZ), and MTX, HCQ, and SSZ in patients with rheumatoid arthritis (RA). Methods RA patients (n = 171) who had not previously been treated with combinations of the study medications were randomized to receive 1 of the 3 treatment combinations in this 2-year, double-blind, placebo-controlled protocol. HCQ was given at a dosage of 200 mg twice a day. The dosage of MTX was accelerated from 7.5 mg/week to 17.5 mg/week in all patients who were not in remission. Similarly, the dosage of SSZ was escalated from 500 mg twice a day to 1 gm twice a day in patients who were not in remission. The primary end point of the study was the percentage of patients who had a 20% response to therapy according to the American College of Rheumatology (ACR) criteria at 2 years. Results Intent-to-treat analysis revealed that patients receiving the triple combination responded best, with 78% achieving an ACR 20% response at 2 years, compared with 60% of those treated with MTX and HCQ (P = 0.05) and 49% of those treated with MTX and SSZ (P = 0.002). Similar trends were seen for the ACR 50% response, with 55%, 40%, and 29% of patients in the 3 treatment groups, respectively, achieving these results at 2 years (P = 0.005 for the triple combination group versus the MTX and SSZ group). All combination treatments were well-tolerated. Fourteen patients (evenly distributed among the 3 groups) withdrew from the protocol because of symptoms that were potentially related to the study medication. Conclusion The triple combination of MTX, SSZ, and HCQ is well-tolerated, and its efficacy is superior to that of the double combination of MTX and SSZ and is marginally superior to that of the double combination of MTX and HCQ. [source] Modeling missing binary outcome data in a successful web-based smokeless tobacco cessation programADDICTION, Issue 6 2010Keith Smolkowski ABSTRACT Aim To examine various methods to impute missing binary outcome from a web-based tobacco cessation intervention. Design The ChewFree randomized controlled trial used a two-arm design to compare tobacco abstinence at both the 3- and 6-month follow-up for participants randomized to either an enhanced web-based intervention condition or a basic information-only control condition. Setting Internet in the United States and Canada. Participants Secondary analyses focused upon 2523 participants in the ChewFree trial. Measurements Point-prevalence tobacco abstinence measured at 3- and 6-month follow-up. Findings The results of this study confirmed the findings for the original ChewFree trial and highlighted the use of different missing-data approaches to achieve intent-to-treat analyses when confronted with substantial attrition. The use of different imputation methods yielded results that differed in both the size of the estimated treatment effect and the standard errors. Conclusions The choice of imputation model used to analyze missing binary outcome data can affect substantially the size and statistical significance of the treatment effect. Without additional information about the missing cases, they can overestimate the effect of treatment. Multiple imputation methods are recommended, especially those that permit a sensitivity analysis of their impact. [source] The efficacy of early propranolol administration at reducing PTSD symptoms in pediatric injury patients: A pilot study,JOURNAL OF TRAUMATIC STRESS, Issue 2 2010Nicole R. Nugent Initial research supports the use of propranolol to prevent posttraumatic stress disorder (PTSD); research has not examined pharmacological prevention for children. Twenty-nine injury patients (ages 10,18 years old) at risk for PTSD were randomized to a double-blind 10-day trial of propranolol or placebo initiated within 12 hours postadmission. Six-week PTSD symptoms and heart rate were assessed. Although intent-to-treat analyses revealed no group differences, findings supported a significant interaction between gender and treatment in medication-adherent participants, ,R2 = .21. Whereas girls receiving propranolol reported more PTSD symptoms relative to girls receiving placebo, ,R2 = .44, boys receiving propranolol showed a nonsignificant trend toward fewer PTSD symptoms than boys receiving placebo, ,R2 = .32. Findings inform gender differences regarding pharmacological PTSD prevention in youth. [source] Secular changes in the quality of published randomized clinical trials in rheumatologyARTHRITIS & RHEUMATISM, Issue 3 2002Catherine L. Hill Objective To assess the quality of published randomized clinical trials (RCTs) in rheumatology and to determine whether there has been improvement in quality between 2 time periods, 1987,1988 and 1997,1998. Methods Using MEDLINE and a hand search of selected rheumatology journals, we identified RCTs of adult rheumatic diseases published in English in 1987,1988 or 1997,1998. We examined trial quality with an expanded version of the Jadad scale, which assesses the adequacy of reported random sequence generation, allocation concealment, blinding, and analysis. All trials were read by 1 reviewer, with prior standardization using a random sample read by 2 reviewers. We also evaluated "high"- versus "low"-impact journals based on citation index. Results Two hundred forty RCTs (1987,1988 119 RCTs, 1997,1998 121 RCTs) were assessed. Results showed improvement in the quality of the trials, but the rates of reported random sequence generation, allocation concealment, power, and intent-to-treat analyses were persistently low. Low rates of reports of random sequence generation, allocation concealment, and intent-to-treat analyses were present even in the high-impact journals. Conclusion There has been improvement in the quality of reporting of RCTs in rheumatology between 1987,1988 and 1997,1998. However, methodologic problems such as lack of allocation concealment, inadequate random sequence generation, lack of reporting of power, and lack of intent-to-treat analyses remain common. Many of these problems are established sources of bias in RCTs and are easily rectifiable. [source] Prognosis and Mechanism of Death in Treated Heart Failure: Data From the Placebo Arm of Val-HeFTCONGESTIVE HEART FAILURE, Issue 3 2006Jay N. Cohn MD The magnitude of benefit on mortality of combined angiotensin-converting enzyme inhibitor (ACEI) and ,-blocker (BB) therapy for heart failure cannot be reliably assessed from prospective randomized trials of individual drugs with intent-to-treat analysis. The placebo arm of the Valsartan Heart Failure Trial (Val-HeFT) included patients who remained on background therapy with ACEIs, BBs, neither, or both. The outcomes in these four subgroups should provide a better guide to mortality benefit. Overall mortality (mean follow-up, 23 months) was 31.6% in those receiving neither neurohormonal blocker, 29% and 39% lower in those on ACEIs or BBs, respectively, and 62% lower (11.9% mortality) in those receiving both drugs. In the neither neurohormonal inhibitor group, 48% of the heart failure-related deaths were adjudicated as sudden, whereas in the group receiving ACEIs and BBs, 79% of the deaths were sudden, and pump failure mortality was only 1% per year. The combination of ACEIs and BBs exerts a greater mortality reduction than suggested from clinical trials and reduces pump failure mortality to 1% per year. [source] Insulin pump therapy vs. multiple daily injections in obese Type 2 diabetic patientsDIABETIC MEDICINE, Issue 8 2005J. Wainstein Abstract Aims To compare the efficacy of insulin pump treatment with multiple daily injections in the treatment of poorly controlled obese Type 2 diabetic patients already receiving two or more daily injections of insulin plus metformin. Methods Forty obese Type 2 diabetic subjects (using insulin) were randomized to treatment with continuous subcutaneous infusion pump (CSII) (Minimed®) or multiple daily insulin injections (MDI). At the end of the first 18-week treatment period, patients underwent a 12-week washout period during which they were treated with MDI plus metformin. They were then crossed-over to the other treatment for an 18-week follow-up period. Patients performed 4-point daily self blood-glucose monitoring (SBGM) on a regular basis and 7-point monitoring prior to visits 2, 8, 10 and 16. A subset of patients underwent continuous glucose monitoring using the Minimed® continuous glucose monitoring system (CGMS) at visits 2, 8, 10 and 16. A standard meal test was performed in which serum glucose was tested at fasting and once each hour for 6 h following a test meal. Glucose levels were plotted against time and the area under the curve (AUC) was calculated. HbA1c, weight, daily insulin dose and hypoglycaemic episodes were recorded. Results In obese Type 2 diabetic patients already treated with insulin, treatment with CSII significantly reduced HbA1c levels compared with treatment with MDI. An additional CSII treatment benefit was demonstrated by reduced meal-test glucose AUC. Initial reduction of daily insulin requirement observed in CSII-treated subjects during the first treatment period was attributable to a period effect and did not persist over time. Conclusions In the intent-to-treat analysis, CSII appeared to be superior to MDI in reducing HbA1c and glucose AUC values without significant change in weight or insulin dose in obese, uncontrolled, insulin-treated Type 2 diabetic subjects. [source] Evaluation of the nano-oligosaccharide factor lipido-colloid matrix in the local management of venous leg ulcers: results of a randomised, controlled trialINTERNATIONAL WOUND JOURNAL, Issue 2 2008Jean-Luc Schmutz Abstract The nano-oligosaccharide factor (NOSF) is a new compound aiming to promote wound closure mainly through inhibition of matrix metalloproteinase (MMP) activity. This factor is incorporated within a lipido-colloid matrix (Techonology Lipido-Colloid-NOSF matrix) and locally released in the wound. The objective of this study was to document the performance (non inferiority or superiority) of the NOSF relative to the Promogran® matrix (oxidised regenerated cellulose, ORC) effect in the local management of venous leg ulcers (VLUs). This was a 12-week, open, two-arm, multicentre, randomised study. Patients were selected if the area of their VLU [ankle brachial pressure index ,0·80] ranged from 5 to 25 cm2 with a duration ,3 months. Ulcers had to be free from necrotic tissue. In addition to receiving compression bandage therapy, patients were randomly allocated to either NOSF matrix or ORC treatment for 12 weeks. The VLUs were assessed on a weekly basis and wound tracings were recorded. Percentage wound relative reduction (%RR) was the primary efficacy criterion. Secondary objectives were wound absolute reduction (AR), healing rate (HR) and % of wounds with ,40% reduction compared with baseline. A total of 117 patients were included (57 NOSF matrix and 60 ORC). Mean population age was 71·3 ± 13·5 years, body mass index was ,30 kg/m2 in 39·3% and 15·4% were diabetics. Fifty-six per cent of the VLUs were present for >6 months, 61% were recurrent and 68% were stagnating despite appropriate care. Mean wound area at baseline was 11·2 ± 7·4 cm2. At the last evaluation, mean difference between the groups for %RR was 33·6 ± 15·0% in favour of NOSF matrix with a unilateral 95% confidence interval (CI) lower limit of 8·6% not including the null value. Therefore, a superiority of NOSF matrix effect compared with ORC was concluded (P = 0·0059 for superiority test). The median of the wound area reduction was 61·1% and 7·7% in the NOSF matrix and control groups, respectively (per-protocol analysis), or 54·4% versus 12·9% in intent-to-treat analysis (p = 0·0286). Median AR was 4·2 cm2 in the NOSF group and 1·0 cm2 with ORC (P = 0·01). Median HR was ,0·056 and ,0·015 cm2/day in NOSF and ORC groups, respectively (P = 0·029). By logistic regression, the NOSF versus control odds ratio to reach 40% area reduction was 2·4 (95% CI: 1·1,5·3; P = 0·026). In the oldest and largest VLUs, a strong promotion of healing effect was particularly observed in the NOSF matrix group compared with the control group. NOSF matrix is a very promising option for the local management of chronic wounds, especially for VLUs with poor healing prognosis. [source] Clinical trial: once-daily mesalamine granules for maintenance of remission of ulcerative colitis , a 6-month placebo-controlled trialALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010G. R. Lichtenstein Aliment Pharmacol Ther 2010; 32: 990,999 Summary Background, Ulcerative colitis (UC) is a chronic relapsing and remitting idiopathic inflammatory bowel disorder. Aim, To evaluate once-daily mesalamine (mesalazine) granules (MG) for maintenance of remission of UC. Methods, Randomized, double-blind, placebo-controlled trial of patients (n = 209 MG, n = 96 placebo) with UC in remission [revised Sutherland Disease Activity Index (SDAI) rectal bleeding = 0, mucosal appearance <2] who took MG 1.5 g or placebo once-daily for up to 6 months. Primary efficacy endpoint: the percentage of patients who remained relapse-free at month 6/end of treatment. Relapse was defined as SDAI rectal bleeding score ,1 and a mucosal appearance score ,2, a UC flare, or initiation of medication to treat a UC flare. Results, The percentage of relapse-free patients at month 6/end of treatment was higher with MG than placebo (78.9% vs. 58.3%, P < 0.001) in the intent-to-treat analysis. Significant differences (P , 0.025) favouring MG were observed for most secondary endpoints including improvement in rectal bleeding, physician's disease activity rating, stool frequency, the SDAI at month 6/end of treatment, patients classified as a treatment success and relapse-free duration. The incidence of adverse events was similar between groups. Conclusions, Once-daily mesalamine (mesalazine) was effective in maintaining remission of UC for 6 months. [source] Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome , results of two randomized, placebo-controlled studiesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009D. A. DROSSMAN Summary Background, Effective treatments for irritable bowel syndrome with constipation (IBS-C) are lacking. Aim, To assess the efficacy and safety of lubiprostone in IBS-C. Methods, A combined analysis was performed among 1171 patients with a Rome II diagnosis of IBS-C in two phase-3 randomized trials of lubiprostone 8 mcg vs. placebo twice daily for 12 weeks. Using a balanced seven-point Likert scale ranging from significantly relieved (+3), to significantly worse (,3), patients responded on their electronic diary to the question: ,How would you rate your relief of IBS symptoms over the past week compared to how you felt before you entered the study?'. The primary efficacy endpoint was the percentage of overall responders. Results, Using an intent-to-treat analysis with last observation carried forward, a significantly higher percentage of lubiprostone-treated patients were considered overall responders compared with those treated with placebo (17.9% vs. 10.1%, P = 0.001). Patients treated with lubiprostone reported a similar incidence of adverse events to those treated with placebo. Conclusions, The percentage of overall responders based on patient-rated assessments of IBS-C symptoms was significantly improved in patients treated with lubiprostone 8 mcg twice daily compared to those treated with placebo. Lubiprostone was well tolerated with a favourable safety profile. [source] Comparison of characteristics of treated and non-treated patients with Hepatitis C infection,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 2 2006C. Bradley Hare MD Abstract Objectives This study compares the characteristics of treated and non-treated patients with Hepatitis C (HCV) infection. Methods Information on patient demographics, clinical data, and treatment regimens were collected from a retrospective medical record review of 998 patients diagnosed with HCV, representing a diverse geographic sample of 200 U.S. physicians including 130 gastroenterologists, 50 infectious disease physicians, and 20 hepatologists. A total of 551 patients were randomly selected and 447 were provided as an augmented sample in an intent-to-treat analysis based on treatment decisions. Pretreatment factors examined included age, gender, race, weight, HCV genotype, HCV viral load, serum ALT levels, liver biopsy results, cirrhosis, HIV co-infection, HBV co-infection, IV drug use, and insurance status. Univariate analyses were performed using Chi-squared or ANOVA tests. Factors that were significant in univariate analyses were entered into a multivariate logistic regression model with HCV treatment as the outcome variable. Results Of the 998 patients reviewed, 778 were treated for HCV and 220 were not treated. In univariate analyses, non-treated patients were more likely to be African American, HBV co-infected, HIV co-infected, IDUs, alcoholics, Medicaid insured, and were less likely to have had biopsies. The multivariate regression analysis demonstrated that performance of a liver biopsy, treatment with psychiatric medications (antidepressants and anxiolytics), and patient weight were independently associated with treatment, while Medicaid insurance and HIV co-infection were independently associated with a decreased likelihood of receiving HCV therapy. Conclusion This study suggests that it is not the clinical stage of HCV infection but the patient's demographic characteristics and co-morbid conditions that impact the decision to initiate HCV therapy. Copyright © 2005 John Wiley & Sons, Ltd. [source] ORIGINAL RESEARCH,FSD PHARMACOTHERAPY: Tibolone and Transdermal E2/NETA for the Treatment of Female Sexual Dysfunction in Naturally Menopausal Women: Results of a Randomized Active-Controlled TrialTHE JOURNAL OF SEXUAL MEDICINE, Issue 3 2008Esme A. Nijland MD ABSTRACT Introduction., There are some data to suggest that tibolone improves sexual function in postmenopausal women. However, evidence about the effects of tibolone on female sexual dysfunction is lacking. Aim., To compare the efficacy on sexual function of tibolone 2.5 mg to continuous combined transdermal estradiol (E2)/norethisterone acetate (NETA) (50 µg/140 µg) in naturally postmenopausal women with sexual dysfunction. Main Outcome Measure., Differences between treatment groups in the change from baseline for the composite subscore of the arousal, desire, and satisfaction domains of the self-reported Female Sexual Function Index (FSFI). Methods., A multicenter, double-blind, randomized, clinical trial was performed. Sexual function was assessed with the FSFI at baseline, week 12, and week 24. The outcomes of the Female Sexual Distress Scale (FSDS) and the frequency of satisfying sexual events (daily diaries) were secondary end points. Results., Four hundred three women, mean age 56, were included. Both therapies improved sexual function assessed by the FSFI. In the per protocol analysis, but not in the intent-to-treat analysis, the increase in FSFI scores was significantly larger in the tibolone group when compared with the E2/NETA patch group at week 24 (P = 0.036 and P = 0.025 for the composite subscore and total FSFI score, respectively). The satisfying sexual event rate increased from three to four times per 28 days at week 24 (P < 0.001 from baseline for both groups), with no difference between groups. The FSDS showed a significant decrease from baseline (P < 0.001), which was comparable for both treatment groups. Conclusions., Both treatments resulted to improved overall sexual function, as determined by scores on the FSFI, an increase in the frequency of sexual events, and a reduction in sexuality-related personal distress. The statistically significant higher FSFI scores in the tibolone group, when compared to the E2/NETA group, may be because of tibolone's combined estrogenic and androgenic properties. Nijland EA, Schultz WCMW, Nathorst-Boös J, Helmond FA, Van Lunsen RHW, Palacios S, Norman RJ, Mulder RJ, and Davis SR for the LISA study investigators. Tibolone and transdermal E2/NETA for the treatment of female sexual dysfunction in naturally menopausal women: Results of a randomized active-controlled trial. J Sex Med 2008;5:646,656. [source] High versus low dosing of oral colchicine for early acute gout flare: Twenty-four,hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study,ARTHRITIS & RHEUMATISM, Issue 4 2010Robert A. Terkeltaub Objective Despite widespread use of colchicine, the evidence basis for oral colchicine therapy and dosing in acute gout remains limited. The aim of this trial was to compare low-dose colchicine (abbreviated at 1 hour) and high-dose colchicine (prolonged over 6 hours) with placebo in gout flare, using regimens producing comparable maximum plasma concentrations in healthy volunteers. Methods This multicenter, randomized, double-blind, placebo-controlled, parallel-group study compared self-administered low-dose colchicine (1.8 mg total over 1 hour) and high-dose colchicine (4.8 mg total over 6 hours) with placebo. The primary end point was ,50% pain reduction at 24 hours without rescue medication. Results There were 184 patients in the intent-to-treat analysis. Responders included 28 of 74 patients (37.8%) in the low-dose group, 17 of 52 patients (32.7%) in the high-dose group, and 9 of 58 patients (15.5%) in the placebo group (P = 0.005 and P = 0.034, respectively, versus placebo). Rescue medication was taken within the first 24 hours by 23 patients (31.1%) in the low-dose group (P = 0.027 versus placebo), 18 patients (34.6%) in the high-dose group (P = 0.103 versus placebo), and 29 patients (50.0%) in the placebo group. The low-dose group had an adverse event (AE) profile similar to that of the placebo group, with an odds ratio (OR) of 1.5 (95% confidence interval [95% CI] 0.7,3.2). High-dose colchicine was associated with significantly more diarrhea, vomiting, and other AEs compared with low-dose colchicine or placebo. With high-dose colchicine, 40 patients (76.9%) had diarrhea (OR 21.3 [95% CI 7.9,56.9]), 10 (19.2%) had severe diarrhea, and 9 (17.3%) had vomiting. With low-dose colchicine, 23.0% of the patients had diarrhea (OR 1.9 [95% CI 0.8,4.8]), none had severe diarrhea, and none had vomiting. Conclusion Low-dose colchicine yielded both maximum plasma concentration and early gout flare efficacy comparable with that of high-dose colchicine, with a safety profile indistinguishable from that of placebo. [source] Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: The randomized, double-blind, phase ii/iii systemic lupus erythematosus evaluation of rituximab trial,ARTHRITIS & RHEUMATISM, Issue 1 2010Joan T. Merrill Objective B cells are likely to contribute to the pathogenesis of systemic lupus erythematosus (SLE), and rituximab induces depletion of B cells. The Exploratory Phase II/III SLE Evaluation of Rituximab (EXPLORER) trial tested the efficacy and safety of rituximab versus placebo in patients with moderately-to-severely active extrarenal SLE. Methods Patients entered with ,1 British Isles Lupus Assessment Group (BILAG) A score or ,2 BILAG B scores despite background immunosuppressant therapy, which was continued during the trial. Prednisone was added and subsequently tapered. Patients were randomized at a ratio of 2:1 to receive rituximab (1,000 mg) or placebo on days 1, 15, 168, and 182. Results In the intent-to-treat analysis of 257 patients, background treatment was evenly distributed among azathioprine, mycophenolate mofetil, and methotrexate. Fifty-three percent of the patients had ,1 BILAG A score at entry, and 57% of the patients were categorized as being steroid dependent. No differences were observed between placebo and rituximab in the primary and secondary efficacy end points, including the BILAG-defined response, in terms of both area under the curve and landmark analyses. A beneficial effect of rituximab on the primary end point was observed in the African American and Hispanic subgroups. Safety and tolerability were similar in patients receiving placebo and those receiving rituximab. Conclusion The EXPLORER trial enrolled patients with moderately-to-severely active SLE and used aggressive background treatment and sensitive cutoffs for nonresponse. No differences were noted between placebo and rituximab in the primary and secondary end points. Further evaluation of patient subsets, biomarkers, and exploratory outcome models may improve the design of future SLE clinical trials. [source] Effect of hyaluronic acid in symptomatic hip osteoarthritis: A multicenter, randomized, placebo-controlled trial,ARTHRITIS & RHEUMATISM, Issue 3 2009Pascal Richette Objective To evaluate the efficacy and tolerability of a single intraarticular (IA) injection of hyaluronic acid (HA) for the treatment of hip osteoarthritis (OA). Methods A multicenter, randomized, parallel-group, placebo-controlled trial was conducted over 3 months. Patients (older than 30 years) with symptomatic hip OA (pain score of >40 mm on a visual analog scale [VAS]) and a Kellgren/Lawrence grade of 2 or 3 were randomly assigned to receive 1 fluoroscopically guided IA injection of HA (2.5 ml) or placebo (2.5 ml). Patients were followed up for 3 months. The main outcome measure was pain score on a VAS (100 mm) at month 3 compared with baseline. Secondary outcome measures were the proportion of responders defined by Osteoarthritis Research Society International criteria; Western Ontario and McMaster Universities Osteoarthritis Index subscores for pain, stiffness, and disability; and patient and physician global assessment. Randomization was computer generated. HA and placebo preparations were placed in numbered identical containers, and syringes were covered with masking tape. Physicians assessing outcomes were blinded with regard to group assignment. Results Eighty-five patients were randomized to the HA group (n = 42) or placebo group (n = 43). Baseline characteristics were similar between the 2 groups. At 3 months, the decrease in pain score did not differ between the HA and placebo groups in the intent-to-treat analysis (mean ± SD decrease 7.8 ± 24.9 mm with HA versus 9.1 ± 27.4 mm with placebo; P = 0.98). The responder rates were 33.3% and 32.6% in the HA and placebo groups, respectively (P = 0.94). Other secondary end points did not differ between the groups, nor did use of rescue medication or frequency of adverse events. Conclusion Our findings indicate that a single IA injection of HA is no more effective than placebo in treating the symptoms of hip OA. [source] Vaccination with selected synovial T cells in rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 2 2007Guangjie Chen Objective This pilot clinical study was undertaken to investigate the role of T cell vaccination in the induction of regulatory immune responses in patients with rheumatoid arthritis (RA). Methods Autologous synovial T cells were selected for pathologic relevance, rendered inactive by irradiation, and used for vaccination. Fifteen patients received T cell vaccination via 6 subcutaneous inoculations over a period of 12 months. Results T cell vaccination led to induction of CD4+ Tregs and CD8+ cytotoxic T cells specific for T cell vaccine. There was selective expansion of CD4+,V,2+ Tregs that produced interleukin-10 (IL-10) and expressed a high level of transcription factor Foxp3, which coincided with depletion of overexpressed BV14+ T cells in treated patients. CD4+ IL-10,secreting Tregs induced by T cell vaccination were found to react specifically with peptides derived from IL-2 receptor ,-chain. The expression level of Foxp3 in CD4+ T cells and increased inhibitory activity of CD4+,CD25+ Tregs were significantly elevated following T cell vaccination. The observed regulatory immune responses collectively correlated with clinical improvement in treated patients. In an intent-to-treat analysis, a substantial response, defined as meeting the American College of Rheumatology 50% improvement criteria, was shown in 10 of the 15 patients (66.7%) and was accompanied by a marked improvement in RA-related laboratory parameters. Conclusion These findings suggest that T cell vaccination induces regulatory immune responses that are associated with improved clinical and laboratory variables in RA patients. [source] Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: A randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator,ARTHRITIS & RHEUMATISM, Issue 2 2007Gabriel Herrero-Beaumont Objective To assess the effects of the prescription formulation of glucosamine sulfate (1,500 mg administered once daily) on the symptoms of knee osteoarthritis (OA) during a 6-month treatment course. Methods Three hundred eighteen patients were enrolled in this randomized, placebo-controlled, double-blind trial in which acetaminophen, the currently preferred medication for symptomatic treatment of OA, was used as a side comparator. Patients were randomly assigned to receive oral glucosamine sulfate 1,500 mg once daily (n = 106), acetaminophen 3 gm/day (n = 108), or placebo (n = 104). The primary efficacy outcome measure was the change in the Lequesne index after 6 months. Secondary parameters included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and response according to the Osteoarthritis Research Society International criteria. These outcome measures were assessed using an intent-to-treat analysis. Results At baseline, the study patients had moderately severe OA symptoms (mean Lequesne index ,11 points). Glucosamine sulfate was more effective than placebo in improving the Lequesne score, with a final decrease of 3.1 points, versus 1.9 with placebo (difference between glucosamine sulfate and placebo ,1.2 [95% confidence interval ,2.3, ,0.8]) (P = 0.032). The 2.7-point decrease with acetaminophen was not significantly different from that with placebo (difference ,0.8 [95% confidence interval ,1.9, 0.3]) (P = 0.18). Similar results were observed for the WOMAC. There were more responders to glucosamine sulfate (39.6%) and acetaminophen (33.3%) than to placebo (21.2%) (P = 0.004 and P = 0.047, respectively, versus placebo). Safety was good, and was comparable among groups. Conclusion The findings of this study indicate that glucosamine sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating knee OA symptoms. Although acetaminophen also had a higher responder rate compared with placebo, it failed to show significant effects on the algofunctional indexes. [source] Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: Two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trialARTHRITIS & RHEUMATISM, Issue 4 2006Désirée van der Heijde Objective To evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease-modifying antirheumatic drug other than MTX had failed. Methods Patients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double-blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent-to-treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals. Results A total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P < 0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P < 0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P < 0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P < 0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups. Conclusion Etanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2-year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX. [source] Effects of tibolone and continuous combined hormone replacement therapy on bleeding rates, quality of life and tolerability in postmenopausal womenBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 8 2002J. Huber Objective To compare the effects of tibolone and conjugated equine oestrogens continuously combined with medroxyprogesterone acetate on bleeding rates, quality of life (QoL) and tolerability. Design A double-blind, randomised comparative trial. Setting Thirty-seven centres in six European countries. Population Five hundred and one postmenopausal women, under 65 years of age with an intact uterus. Interventions For 12 months, women received daily treatment with tibolone 2.5 mg (n= 250), or conjugated equine oestrogens 0.625 mg continuously combined with medroxyprogesterone acetate 5 mg (CEE,MPA, n= 251). Main outcome measures The primary outcome was vaginal bleeding rate during cycles 4,6. The secondary outcomes were vaginal bleeding rate during cycles 1,3, 7,9 and 10,13, cumulative bleeding rate, QoL, wellbeing, climacteric symptoms, urogenital complaints and tolerability. Results Treatment with tibolone led to a significantly lower bleeding rate during cycles 4,6 compared with CEE,MPA (15.0%vs 26.9%; P= 0.004); there was a similar difference during cycles 1,3. Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital complaints. By intent-to-treat analysis, tibolone significantly improved sexual drive, interest and/or performance, compared with CEE,MPA at 12 months (P= 0.017). Although both treatments were well tolerated, there was a significantly lower incidence of breast tenderness with tibolone than CEE,MPA (2.4%vs 17.1%; P < 0.001). Conclusion The vaginal bleeding rate during cycles 4,6 was significantly lower in women using tibolone. Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital symptoms. Breast tenderness was significantly less frequent with tibolone. [source] A Phase II study of gemcitabine and cisplatin in advanced biliary tract cancerCANCER, Issue 6 2006Seung Tai Kim M.D. Abstract BACKGROUND The authors performed a Phase II study of combination chemotherapy with gemcitabine and cisplatin in patients with inoperable biliary tract cancer to evaluate efficacy and toxicity of this combination. In addition, the correlation between the CA 19-9 response and clinical outcome was analyzed. METHODS The eligibility criteria for this study were 1) histologically or cytologically confirmed inoperable biliary tract cancer in patients with metastatic or recurrent disease; 2) age between 18 and 70 years; 3) at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria; 4) an Eastern Cooperative Oncology Group (ECOG) performance status , 2; 5) a life expectancy of at least 3 mos; and 6) adequate bone marrow, hepatic, and renal function. The patients received gemcitabine (1250 mg/m2, Days 1 and 8) and cisplatin (60 mg/m2, Day 1) every 3 weeks. Tumor response was assessed by RECIST criteria every 2 cycles of chemotherapy. Treatment was continued until progression of disease was documented. RESULTS Twenty-nine patients were enrolled. The median age of these patients was 52 years (range, 37 to 69 yrs), and the median ECOG performance status was 1. No complete response was observed, and 10 of 29 patients had partial responses. The overall response rate was 34.5% (95% confidence interval [CI], 17.9,54.3) for the intent-to-treat analysis. Stable disease was observed in 4 (13.8%) patients and progressive disease in 13 (44.8%) patients. The median follow-up time was 10.0 months (95% CI, 7.2,12.8). The median time to progression (TTP) was 3.0 months (95% CI, 2.12,3.88), and the median overall survival was 11 months (95% CI, 5.49,16.5). Although these results showed a better response rate (57.1 % vs. 27.3%) and survival (12 vs. 10 mos) in patients with a decline in CA 19-9 of at least 25%, these data were statistically not significant. In addition, there was a significant positive correlation between the increment in CA 19-9 values and tumor progression as determined with RECIST criteria (r = 0.96, P < 0.01). However, there was no definite correlation between the CA 19-9 response and the response according to RECIST criteria (P = 0.087). National Cancer Institute (NCI) common toxicity criteria (CTC) Grade 3 or 4 hematologic toxicities included neutropenia in 4 (14%) patients and anemia in 1 (3%) patient. Two of 4 patients with Grade 3 or 4 neutropenia had febrile episodes (7%) and required hospital admissions. NCI-CTC Grade 3 or 4 nonhematologic toxicity included nausea in 1 (3%) patient. There were no treatment-related deaths. CONCLUSION The combination chemotherapy with gemcitabine and cisplatin in inoperable biliary tract cancer was tolerable for most patients and showed modest response rates. The role of CA 19-9 monitoring as a surrogate biomarker in patients with BTC treated with gemcitabine chemotherapy should be further investigated. Cancer 2006. © 2006 American Cancer Society. [source] | ||||||||||