Systematic Empirical vs. Test-guided Anti-tuberculosis Treatment Impact in Severely Immunosuppressed HIV-infected Adults Initiating Antiretroviral Therapy With CD4 Cell Counts <100/mm3: the STATIS Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 1,050
- 试验地点
- 4
- 主要终点
- All-cause mortality and incidence of invasive bacterial infections
研究概览
简要总结
In countries with a high tuberculosis (TB) prevalence, TB and invasive bacterial infections are leading causes of early death in patients who initiate antiretroviral therapy (ART) with advanced immunodeficiency.
We hypothesize that a systematic 6-month empirical TB treatment initiated 2 weeks before the introduction of ART in HIV-infected adults with severe immunosuppression (CD4<100/mm3) and no overt evidence of TB will reduce the risk of death and invasive bacterial infections. This strategy will be compared to one of extensive TB testing using point-of-care tests (Xpert MTB/RIF® and urine lipoarabinomanan LAM) and chest X-ray to identify and treat only patients with at least one positive test suggestive of TB.
详细描述
Settings: Cambodia, Côte d'Ivoire, Uganda, Vietnam. Design: Multicentre, two-arm, unblinded randomized controlled superiority trial.
Objective: To compare the 24-week risk of death and occurrence of invasive bacterial infection between two experimental strategies in HIV-1 infected adults who start ART with a CD4 count <100/mm3: (i) continuous extensive TB screening during follow-up each time the patient present with symptoms, versus (ii) systematic empirical TB treatment started 2 weeks before ART initiation.
Trial strategies:
At inclusion, participants will be randomized 1:1 in two strategies of TB testing and treatment: extensive TB screening, or systematic empirical TB treatment.
Extensive TB screening (arm 1): In this arm:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years;
- •HIV-1 infection as documented at any time prior to trial entry, as per national testing procedures;
- •CD4 <100 cells/mm3;
- •No history of antiretroviral drug use (except transient ART for PMTCT);
- •Able to correctly understand the trial and to sign the informed consent.
排除标准
- •HIV-2 co-infection;
- •Contra-indication to efavirenz;
- •Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >5 times the upper limit of normal;
- •Creatinine clearance <50 ml/min;
- •Overt evidence that TB treatment should be started immediately;
- •History of TB treatment in the past 5 years;
- •Ongoing TB chemoprophylaxis (isoniazid preventive therapy);
- •Any condition that would lead to differ ART initiation (e.g. acute condition requiring investigations and/or treatment prior to ART initiation);
- •Current pregnancy or breastfeeding.
研究组 & 干预措施
Xpert MTB/RIF®, Determine TB LAM, Chest X-ray
Arm1 Extensive TB screening:
In this arm, point-of-care tests for TB will be used at randomization (in all patients) and at each scheduled or unscheduled follow-up visit (in patients with signs or symptoms suggestive of TB and no clear alternative diagnosis); TB treatment will only be prescribed to patients with a diagnosis of TB
干预措施: Xpert MTB/RIF®, Determine TB LAM, Chest X-ray (Device)
Xpert MTB/RIF®, Determine TB LAM, Chest X-ray
Arm1 Extensive TB screening:
In this arm, point-of-care tests for TB will be used at randomization (in all patients) and at each scheduled or unscheduled follow-up visit (in patients with signs or symptoms suggestive of TB and no clear alternative diagnosis); TB treatment will only be prescribed to patients with a diagnosis of TB
干预措施: ART (Atripla, Truvada, Efavirenz, Combivir) (Drug)
Xpert MTB/RIF®, Determine TB LAM, Chest X-ray
Arm1 Extensive TB screening:
In this arm, point-of-care tests for TB will be used at randomization (in all patients) and at each scheduled or unscheduled follow-up visit (in patients with signs or symptoms suggestive of TB and no clear alternative diagnosis); TB treatment will only be prescribed to patients with a diagnosis of TB
干预措施: Rifampin, isoniazid, pyrazinamide, ethambutol (Drug)
Rifampin, isoniazid, pyrazinamide, ethambutol
Arm 2: Systematic Empiric treatment (Rifampicin,isoniazid, pyrazinamide, ethambutol) ART
In this arm, all patients will start a systematic 6-month TB treatment at randomization. TB screening tests will not systematically be used neither at randomization nor while patients are on TB treatment.
干预措施: ART (Atripla, Truvada, Efavirenz, Combivir) (Drug)
Rifampin, isoniazid, pyrazinamide, ethambutol
Arm 2: Systematic Empiric treatment (Rifampicin,isoniazid, pyrazinamide, ethambutol) ART
In this arm, all patients will start a systematic 6-month TB treatment at randomization. TB screening tests will not systematically be used neither at randomization nor while patients are on TB treatment.
干预措施: Rifampin, isoniazid, pyrazinamide, ethambutol (Drug)
结局指标
主要结局
All-cause mortality and incidence of invasive bacterial infections
时间窗: 24 weeks
The primary endpoint is the composite of (i) 24-week all-cause mortality and (ii) 24-week incidence of invasive bacterial infections
次要结局
- Incidence of confirmed/probable/possible TB(24 Weeks and 48 weeks)
- Incidence of grade 3 or 4 adverse events(24 Weeks and 48 weeks)