PLoS clinical trials最新文献

Objectives: To respond to the primary safety objective of the Perinatal HIV Prevention Trial 1 (PHPT-1) by studying the evolution of haematological parameters according to zidovudine exposure duration in HIV-1-infected pregnant women.

Design: Multicenter, randomized, double-blind, controlled trial of different durations of zidovudine prophylaxis.

Setting: 27 hospitals in Thailand.

Participants: 1,436 HIV-infected pregnant women in PHPT-1.

Intervention: Zidovudine prophylaxis initiation at 28 or 35 wk gestation.

Outcome measures: Haemoglobin level, leucocytes, total lymphocyte counts, and absolute neutrophil counts were measured at 26, 32, and 35 wk and at delivery. The evolution of haematological parameters was estimated between 26 and 35 wk (zidovudine/placebo) and between 35 wk and delivery to compare a long versus short zidovudine exposure. For each parameter, linear mixed models were adjusted on baseline sociodemographic variables, HIV clinical stage, CD4 count, and viral load.

Results: Between 26 and 35 wk, haemoglobin, leucocytes, and absolute neutrophil counts decreased in zidovudine-exposed compared to unexposed women (mean difference [95% CI] -0.4 [-0.5 to -0.3], -423 [-703 to -142], -485 [-757 to -213], respectively). However, between 35 wk and delivery, the haematological parameters increased faster in women exposed to long rather than short durations of zidovudine (0.1 [0.0 to 0.1]; 105 [18 to 191]; 147 [59 to 234], respectively). At delivery, the differences were not statistically significant, except for mean haemoglobin level, which remained slightly lower in the long zidovudine treatment group (difference: 0.2 g/dl). Zidovudine had no negative impact on the absolute lymphocyte counts.

Conclusion: Zidovudine initiated at 28 wk gestation rather than 35 wk had a transient negative impact on the evolution of haematological parameters, which was largely reversed by delivery despite continuation of zidovudine. This result provides reassurance about the safety of early initiation of zidovudine prophylaxis during pregnancy to maximize prevention of perinatal HIV.

Objectives: Indigenous medicines are widely used throughout Africa, despite a lack of scientific evidence for their safety or efficacy. The aims of this study were: (a) to conduct a pilot study of the safety of a common indigenous South African phytotherapy, Lessertia frutescens (Sutherlandia), in healthy adults; and (b) to contribute to establishing procedures for ethical and scientifically rigorous clinical trials of African indigenous medicines.

Design: A randomized, double-blind, placebo-controlled trial of Sutherlandia leaf powder in healthy adults.

Setting: Tiervlei Trial Centre, Karl Bremer Hospital, Bellville, South Africa.

Participants: 25 adults who provided informed consent and had no known significant diseases or allergic conditions nor clinically abnormal laboratory blood profiles during screening.

Intervention: 12 participants randomized to a treatment arm consumed 400 mg capsules of Sutherlandia leaf powder twice daily (800 mg/d). 13 individuals randomized to the control arm consumed a placebo capsule. Each participant received 180 capsules for the trial duration of 3 mo.

Outcome measures: The primary endpoint was frequency of adverse events; secondary endpoints were changes in physical, vital, blood, and biomarker indices.

Results: There were no significant differences in general adverse events or physical, vital, blood, and biomarker indices between the treatment and placebo groups (p > 0.05). However, participants consuming Sutherlandia reported improved appetite compared to those in the placebo group (p = 0.01). Although the treatment group exhibited a lower respiration rate (p < 0.04) and higher platelet count (p = 0.03), MCH (p = 0.01), MCHC (p = 0.02), total protein (p = 0.03), and albumin (p = 0.03), than the placebo group, these differences remained within the normal physiological range, and were not clinically relevant. The Sutherlandia biomarker canavanine was undetectable in participant plasma.

Conclusion: Consumption of 800 mg/d Sutherlandia leaf powder capsules for 3 mo was tolerated by healthy adults.

Objectives: To determine the efficacy of adding abacavir (Ziagen, ABC) to optimal stable background antiretroviral therapy (SBG) to AIDS dementia complex (ADC) patients and address trial design.

Design: Phase III randomized, double-blind placebo-controlled trial.

Setting: Tertiary outpatient clinics.

Participants: ADC patients on SBG for > or = 8 wk.

Interventions: Participants were randomized to ABC or matched placebo for 12 wk.

Outcome measures: The primary outcome measure was the change in the summary neuropsychological Z score (NPZ). Secondary measures were HIV RNA and the immune activation markers beta-2 microglobulin, soluble tumor necrosis factor (TNF) receptor 2, and quinolinic acid.

Results: 105 participants were enrolled. The median change in NPZ at week 12 was +0.76 for the ABC + SBG and +0.63 for the SBG groups (p = 0.735). The lack of efficacy was unlikely related to possible limited antiviral efficacy of ABC: at week 12 more ABC than placebo participants had plasma HIV RNA < or = 400 copies/mL (p = 0.002). There were, however, other factors. Two thirds of patients were subsequently found to have had baseline resistance to ABC. Second, there was an unanticipated beneficial effect of SBG that extended beyond 8 wk to 5 mo, thereby rendering some of the patients at baseline unstable. Third, there was an unexpectedly large variability in neuropsychological performance that underpowered the study. Fourth, there was a relative lack of activity of ADC: 56% of all patients had baseline cerebrospinal fluid (CSF) HIV-1 RNA < 100 copies/mL and 83% had CSF beta-2 microglobulin < 3 nmol/L at baseline.

Conclusions: The addition of ABC to SBG for ADC patients was not efficacious, possibly because of the inefficacy of ABC per se, baseline drug resistance, prolonged benefit from existing therapy, difficulties with sample size calculations, and lack of disease activity. Assessment of these trial design factors is critical in the design of future ADC trials.

Objectives: To assess the efficacy of an acute multidisciplinary group intervention on self-perceived recovery following minor traffic-related musculoskeletal injuries.

Design: Open, randomized controlled trial.

Setting: A large inner-city hospital.

Participants: 127 patients (> or = 15 y) with traffic-related acute minor musculoskeletal injuries and predicted to be at risk for delayed recovery were randomized into an intervention group (n = 65) or a control group (n = 62).

Intervention: Four 1 1/2-h sessions in open groups with the aim of providing information about injuries in general, calling attention to the importance of self-care and promoting physical activity. In addition, both groups received standard medical care by regular staff.

Outcome measures: The main outcome measure was self-reported recovery at 12 mo. Secondary outcome measures were ratings of functional health status (SF-36, SMFA), pain and mental distress on visual analog scales, and self-reported duration of sick leave.

Results: At 12 mo, there was a 21.9 percentage point difference: 52.4% of the patients in the intervention group and 30.5% in the control group reported self-perceived recovery (95% confidence interval for the difference 5%-38%; p = 0.03). There were no statistically significant differences between the groups regarding the secondary outcome measures.

Conclusion: A simple group intervention may accelerate the self-perceived recovery in selected patients. As we did not find evidence of improvements in the secondary outcome measures, the clinical significance of the treatment benefit remains to be defined.

Objectives: To evaluate the short-term symptomatic efficacy of rofecoxib and diclofenac versus placebo in acute episodes of shoulder pain.

Design: Randomized controlled trial of 7 days.

Setting: Rheumatologists and/or general practitioners totaling 47.

Participants: Acute shoulder pain.

Interventions: Rofecoxib 50 mg once daily, diclofenac 50 mg three times daily, and placebo.

Outcome measures: Pain, functional impairment, patient's global assessment of his/her disease activity, and local steroid injection requirement for persistent pain. The primary variable was the Kaplan-Meier estimates of the percentage of patients at day 7 fulfilling the definition of success (improvement in pain intensity and a low pain level sustained to the end of the 7 days of the study; log-rank test).

Results: There was no difference in the baseline characteristics between the three groups (rofecoxib n = 88, placebo n = 94, and diclofenac n = 89). At day 7, the Kaplan-Meier estimates of successful patients was higher in the treatment groups than in the placebo (54%, 56%, and 38% in the diclofenac, rofecoxib, and placebo groups respectively, p = 0.0070 and p = 0.0239 for placebo versus rofecoxib and diclofenac, respectively). During the 7 days of the study, there was a statistically significant difference between placebo and both active arms (rofecoxib and diclofenac) in all the evaluated outcome measures A local steroid injection had to be performed in 33 (35%) and 19 (22%) patients in the placebo and rofecoxib group respectively. Number needed to treat to avoid such rescue therapy was 7 patients (95% confidence interval 5-15).

Conclusion: This study highlights the methodological aspects of clinical trials, e.g., eligibility criteria and outcome measures, in acute painful conditions. The data also establish that diclofenac and rofecoxib are effective therapies for the management of acute painful shoulder and that they reduce the requirement for local steroid injection.

Objective: Assess efficacy of intermittent intravaginal metronidazole gel treatment in reducing frequency of bacterial vaginosis (BV).

Design: Randomized, double-masked, placebo-controlled phase 3 trial.

Setting: Postnatal and family planning clinics of the Queen Elizabeth Central Hospital and two health centers in Blantyre, Malawi.

Participants: Nonpregnant HIV-uninfected and -infected women.

Intervention: Intravaginal metronidazole treatment and placebo gels provided at baseline and every 3 mo for 1 y.

Outcome measures: PRIMARY: Cross-sectional and longitudinal comparisons of BV frequency at baseline, 1 mo after product dispensation (post-treatment evaluation [PTE]), and every quarterly visit. Secondary: Effect of treatment on BV clearance and recurrence.

Results: BASELINE: 842 HIV-uninfected and 844 HIV-infected women were enrolled. The frequency of BV at baseline in treatment and placebo arms, respectively, was 45.9% and 46.8% among HIV-uninfected women, and 60.5% and 56.9% among HIV-infected women.

Primary outcomes: At the PTEs the prevalence of BV was consistently lower in treatment than placebo arms irrespective of HIV status. The differences were statistically significant mainly in HIV-uninfected women. Prevalence of BV was also reduced over time in both treatment and placebo arms. In a multivariable analysis that controlled for other covariates, the effect of intravaginal metronidazole treatment gel compared with placebo was not substantial: adjusted relative risk (RR) 0.90, 95% confidence interval (CI) 0.83-0.97 in HIV-uninfected women and adjusted RR 0.95, 95% CI 0.89-1.01 in HIV-infected women.

Secondary outcomes: Intravaginal metronidazole treatment gel significantly increased BV clearance (adjusted hazard ratio [HR] 1.34, 95% CI 1.07-1.67 among HIV-uninfected women and adjusted HR 1.29, 95% CI 1.06-1.58 among HIV-infected women) but was not associated with decreased BV recurrence.

Safety: No serious adverse events were related to use of intravaginal gels.

Conclusion: Intermittent microbicide treatment with intravaginal gels is an innovative approach that can reduce the frequency of vaginal infections such as BV.