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Placebo Recipients (placebo + recipient)
Selected AbstractsFactors associated with incarceration and incident human immunodeficiency virus (HIV) infection among injection drug users participating in an HIV vaccine trial in Bangkok, Thailand, 1999,2003ADDICTION, Issue 2 2009Pravan Suntharasamai ABSTRACT Aims To determine if incarceration was associated with human immunodeficiency virus (HIV) infection and identify risk factors for incarceration among injection drug users (IDUs) participating in an HIV vaccine trial in Bangkok. Design The AIDSVAX B/E HIV vaccine trial was a randomized, double-blind, placebo-controlled study. A proportional hazards model was used to evaluate demographic characteristics, risk behavior and incarceration as predictors of HIV infection and generalized estimation equation logistic regression analysis to investigate demographic characteristics and risk behaviors for predictors of incarceration. Setting The trial was conducted in Bangkok Metropolitan Administration drug-treatment clinics, 1999,2003. Participants A total of 2546 HIV-uninfected IDUs enrolled in the trial. Measurements HIV testing was performed and an interviewer-administered questionnaire was used to assess risk behavior and incarceration at baseline and every 6 months for a total of 36 months. Findings HIV incidence was 3.4 per 100 person-years [95% confidence interval (CI), 3.0,3.9] and did not differ among vaccine and placebo recipients. In multivariable analysis, being in jail (P < 0.04), injecting (P < 0.0001), injecting daily (P < 0.0001) and sharing needles (P = 0.02) were associated with HIV infection and methadone maintenance was protective (P = 0.0006). Predictors of incarceration in multivariable analysis included: male sex (P = 0.04), younger age (P < 0.0001), less education (P = 0.001) and being in jail (P < 0.0001) or prison (P < 0.0001) before enrollment. Conclusions Among IDUs in the AIDSVAX B/E trial, incarceration in jail was associated with incident HIV infection. IDUs in Thailand remain at high risk of HIV infection and additional prevention tools are needed urgently. HIV prevention services, including methadone, should be made available to IDUs. [source] Vaccination trial with HPV16 L1E7 chimeric virus-like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3)INTERNATIONAL JOURNAL OF CANCER, Issue 12 2007Andreas M. Kaufmann Abstract Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus-like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric virus-like particles (CVLP) consist of a carboxy-terminally truncated HPV16L1 protein fused to the amino-terminal part of the HPV16 E7 protein and self-assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1- and E7-specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A randomized, double blind, placebo-controlled clinical trial has been conducted in 39 HPV16 mono-infected high grade cervical intraepithelial neoplasia (CIN) patients (CIN 2/3). Two doses (75 ,g or 250 ,g) of CVLP were applied. The duration of the study was 24 weeks with 2 optional visits after another 12 and 24 weeks. The vaccine showed a very good safety profile with only minor adverse events attributable to the immunization. Antibodies with high titers against HPV16 L1 and low titers against HPV16 E7 as well as cellular immune responses against both proteins were induced. Responses were equivalent for both vaccine concentrations. A trend for histological improvement to CIN 1 or normal was seen in 39% of the patients receiving the vaccine and only 25% of the placebo recipients. Fifty-six percent of the responders were also HPV16 DNA-negative by the end of the study. Therefore, we demonstrated evidence for safety and a nonsignificant trend for the clinical efficacy of the HPV16 L1E7 CVLP vaccine. © 2007 Wiley-Liss, Inc. [source] Clinical trial: the effects of certolizumab pegol therapy on work productivity in patients with moderate-to-severe Crohn's disease in the PRECiSE 2 studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2010B. G. FEAGAN Aliment Pharmacol Ther,31, 1276,1285 Summary Background, The effect of certolizumab pegol on employment status and work productivity has not been previously assessed. Aim, To assess the impact of treatment with certolizumab pegol, the only PEGylated, Fab, TNF antagonist, on work productivity in patients with active Crohn's disease (CD) from the PRECiSE 2 study. Methods, Patients (n = 668) with active disease [CD activity index (CDAI) score of 220,450] were treated with open-label subcutaneous certolizumab pegol 400 mg (week 0, 2, 4). Responders (n = 425) (,100-point decrease in CDAI from baseline) were randomized to receive certolizumab pegol 400 mg or placebo every 4 weeks until week 24, with final evaluation at week 26. Patients completed the Work Productivity and Activity Impairment for CD questionnaire (WPAI:CD) and the Inflammatory Bowel Disease Questionnaire (IBDQ) at weeks 0, 6, 16 and 26 and at the withdrawal visit. Results, Work productivity improved following induction with certolizumab pegol. Between week 6 and 26, certolizumab pegol-treated patients experienced significant improvement in work productivity compared with placebo recipients (11% and 10% overall improvement in work and activity impairment, respectively). During the maintenance phase, impairments in productivity and activities due to CD were significantly less in the certolizumab pegol group than in the placebo group. Conclusion, Induction and maintenance therapy with certolizumab pegol significantly improved the work productivity of patients with active CD compared with those in the placebo group. [source] Humoral immune responses during a malaria vaccine trial in Tanzanian infantsPARASITE IMMUNOLOGY, Issue 9 2000Galindo The development of a malaria vaccine is a priority for improved and sustained malaria control. Optimal use of a vaccine in Africa will only be achieved if it can be delivered through the Expanded Programme of Immunization (EPI). We have completed a trial of the peptide vaccine SPf66 in Tanzanian infants, given alongside the EPI vaccines. This paper describes the humoral responses to SPf66 and the EPI vaccines. A total of 1207 infants were recruited into a two-arm, double-blind, individually randomized placebo-controlled trial of SPf66. The objectives of the trial were to determine the safety, immunogenicity and efficacy of SPf66 and to assess interactions with EPI vaccines when three doses of SPf66 were delivered alongside the EPI vaccines. Cross-sectional surveys were carried out to asses seroconversion rates to the EPI vaccines and the antibody response to SPf66 (NANP)50 and Plasmodium falciparum lysates. Seroconversion rates to EPI vaccines were high and no statistically significant differences in prevalence or titres were found between SPf66 and placebo recipients. IgG antibodies against SPf66 (NANP)50 and whole P. falciparum lysate were present in high titres in mothers of recruited children at the time of birth. Vaccination with SPf66 stimulated a good anti-SPf66 IgG response which declined to preimmunization levels by 2 years of age and which was not associated with protection against clinical malaria. The vaccine induced no IgG antibodies against (NANP)50 or P. falciparum lysates. SPf66 stimulated a humoral immune response when given to very young infants and did not interfere with seroconversion to EPI vaccines. The response to SPf66 was qualitatively different from that seen in older children, in whom SPf66 has been shown to be moderately efficacious. This difference raises concerns about the difficulties of immunizing very young infants who need to be targeted by antimalarial vaccination programs. [source] An investigation of dose titration with darifenacin, an M3 -selective receptor antagonistBJU INTERNATIONAL, Issue 4 2005William Steers OBJECTIVES To evaluate the efficacy, tolerability and safety of a flexible-dosing strategy with darifenacin, an M3 -selective receptor antagonist, in patients with symptoms of overactive bladder (OAB). PATIENTS AND METHODS In this multicentre double-blind 12-week study, 395 patients (aged 22,89 years; 84% female) with OAB symptoms for >6 months were randomized (2 : 1) and received once-daily treatment with darifenacin controlled-release tablets 7.5 mg (268 patients) or matching placebo (127). After 2 weeks of treatment, the efficacy, safety and tolerability were assessed and the dose increased to 15 mg once daily (pseudo-increase for placebo recipients) if additional efficacy was required by both the patient and physician. In the week before clinic visits (at 2 and 12 weeks), patients recorded incontinence episodes (primary efficacy endpoint) and several secondary efficacy variables in an electronic daily diary. Safety and tolerability were evaluated from withdrawal rates and adverse-event reports. RESULTS The treatment groups had comparable baseline characteristics. Similar proportions of darifenacin (59%) and placebo (68%) recipients increased the dose at 2 weeks; at 12 weeks patients on darifenacin (overall group) had a significantly greater reduction in the median number of incontinence episodes per week than had those on placebo, at ,,8.2 (,62.9%) and ,,6.0 (,48.1%), respectively (P = 0.035). There were also significant improvements in voiding frequency (P = 0.001), bladder capacity (volume voided; P=,0.036), frequency of urgency (P < 0.001), severity of urgency (P = 0.013) and number of significant leaks/week (i.e. incontinence episodes needing a change of clothing or pads, per week; P = 0.010) for darifenacin over placebo. Subset analysis suggested that some patients (those remaining on darifenacin 7.5 mg) were more sensitive to darifenacin than those who increased the dose, based on both efficacy and adverse events. Continued treatment with 7.5 mg for ,sensitive' patients, and an increased dose (to 15 mg) for remaining patients, resulted in comparable outcomes by 12 weeks. The most common treatment-related adverse events were mild-to-moderate dry mouth and constipation, which led to discontinuation in <,3.0% of darifenacin-treated patients and <1.0% of the placebo group. Central nervous system and cardiovascular adverse events were comparable to those with placebo. CONCLUSIONS Darifenacin appears to be an effective, well-tolerated and flexible treatment for patients with OAB, allowing individualized dosing according to patient needs. [source] Alpha-dihydroergocryptine in the treatment of de novo parkinsonian patients: results ofa multicentre, randomized, double-blind, placebo-controlled studyACTA NEUROLOGICA SCANDINAVICA, Issue 6 2000B. Bergamasco Introduction, A multicentre, randomized, double-blind, placebo-controlled, parallel group study was carried out in 123 patients suffering from never treated (de novo) idiopathic Parkinson's disease (PD). The aim of the study was to confirm the efficiency and safety of ,-dihydroergocryptine (,-DHEC) given as monotherapy in the symptomatic treatment of PD. The total score of the Unified Parkinson's Disease Rating Scale (UPDRS) was identified as the efficacy target variable. Patients and methods, Sixty-two patients (32 males, 30 females, mean age±SD 64±10) were randomized to ,-dihydroergocryptine and 61 (30 males, 31 females, mean age 63.8±9.1) to placebo. According to the experimental design, a 18-month double-blind phase vs placebo was followed. Two interim analyses were planned both at the 3rd and 12th month of treatment, in order to avoid continuation on placebo, if clear differences between groups were found (stopping criterium: nominal significance level equal to 0.022 in the analysis of the target variable). Analysis of variance was performed both on the per protocol (PP) and intent-to-treat (ITT) sample. Results, The results on the first interim analysis showed significant differences between treatment groups of the UPDRS total score both in the ITT (115 patients, ,-DHEC: No. 56; placebo: No. 59; P=0.019) and PP (96 patients, ,-DHEC: No. 46; placebo: No. 50; P=0.001) sample, why the trial was stopped. At the time of stopping the trial, 73 patients (,-DHEC: No. 37; placebo: No. 36) had reached the 6-month observation visit; the analysis carried out on this subset of patients confirmed the efficacy of ,-dihydroergocryptine in early PD and the correctness of the decision to stop. The incidence of adverse drug reactions (ADR) did not differ between ,-dihydroergocryptine and placebo recipients, gastrointestinal complaints being the most frequent. Conclusion, The results indicate that ,-dihydroergocryptine is safe and effective in improving symptoms of de novo parkinsonian patients. [source] | ||||||||||