ANRS 12424: Determination of Adequate Tuberculosis Regimen in Adults and Adolescents Hospitalized With HIV-associated Severe Immune Suppression (CD4 ≤ 100 Cells/µL): the DATURA Trial.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,330
- 试验地点
- 6
- 主要终点
- Rate of all causes death
研究概览
简要总结
DATURA trial is a phase III, multicenter, two-arm, open-label, randomized superiority trial to compare the efficacy and the safety of an intensified tuberculosis (TB) regimen versus standard TB treatment in HIV-infected adults and adolescents hospitalized for TB with CD4 ≤ 100 cells/μL over 48 weeks:
- Intensified TB treatment regimen: increased doses of rifampicin and isoniazid together with standard-dose of pyrazinamide and ethambutol for 8 weeks in addition to prednisone for 6 weeks and albendazole for 3 days
- WHO standard TB treatment regimen.
The continuation phase of TB treatment will be identical in the two arms: 4 months of rifampicin and isoniazid at standard doses.
详细描述
Settings: 5 African (Cameroon, Guinea, Uganda, Zambia, Mozambique) and 1 South-East Asian (Cambodia) countries.
Sample size : 1330 patients (665 in each arm). Follow-up : 48 weeks after entry in the trial (TB treatment initiation).
All participants will initiate antiretroviral therapy (ART) 2 weeks after starting TB treatment. In each country, the chosen ART regimen will be the same in both arms. According to the first-line regimen recommended in each country, the ART combination will be TDF/3TC/EFV 600 mg, or TDF/3TC + double-dose DTG.
The primary objective is to estimate the impact of an intensified initial phase of TB treatment on mortality at 48 weeks among HIV-infected adults and adolescents hospitalized for TB with CD4 ≤ 100 cells/μL in comparison with standard TB treatment.
The secondary objectives are to estimate the impact of an intensified initial phase of TB treatment, in comparison with the standard TB regimen, on:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Intensified TB treatment
- Increased doses of rifampicin (R) to 35±5 mg/kg daily and isoniazid (H) 10±2 mg/kg daily together with standard-dose of pyrazinamide (Z) 20-30 mg/kg daily + ethambutol (E) 15-20 mg/kg daily for 8 weeks (initial phase of TB treatment).
- Prednisone 40 to 80 mg once a day (OD) according to weight bands for 2 weeks, followed by 20 to 40 mg OD according to weight bands for 2 weeks, then 10 to 20 mg OD according to weight bands for the last 2 weeks (total duration: 6 weeks). Because of the corticosteroid treatment, albendazole 400 mg OD will be given to participants for 3 days.
- Continuation phase: 16 weeks of RH.
干预措施: Intensified TB treatment (initial phase) (Drug)
WHO standard TB treatment
- Standard-dose of R 8-12 mg/kg daily + H 4-6 mg/kg daily + Z 20-30 mg/kg daily + E 15-20 mg/kg daily for 8 weeks.
- Continuation phase: 16 weeks of RH.
干预措施: WHO standard TB treatment (initial phase) (Drug)
结局指标
主要结局
Rate of all causes death
时间窗: Up to 48 weeks
Number of deaths between the inclusion visit and week 48, divided by the total person-years of follow-up until week 48
次要结局
- Rate of all causes death(Up to 24 weeks)
- Rate of adverse events(Up to 48 weeks)
- Rate of AIDS-defining illnesses(Up to 48 weeks)
- Rate of paradoxical TB-associated IRIS(Up to 14 weeks)
- Rate of TB treatment success(Up to 24 weeks)
- Rate of TB recurrence(Up to 48 weeks)
- Rate of virological success(Week 48)
- Adherence to TB and ART treatment(up to 24 weeks)
- Immunological response(Up to 48 weeks)
- Plasma concentrations of rifampicin and isoniazid(Up to 2 weeks)
- Plasma concentrations of efavirenz and dolutegravir(Week 4)