NCT01442428撤回2 期
Randomized Controlled Trial for Corticosteroids Versus NSAIDs With or Without Adjunctive Atorvastatin for the Treatment for Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 3
- 主要终点
- Change in Clinical Symptom Score at Day 7, as measured by the 10-point visual analog scale to quantify symptom severity.
研究概览
简要总结
Tuberculosis is the most common opportunistic infection (OI) in HIV-infected persons worldwide, including in South East Asia. Significant numbers of patients experience tuberculosis-related paradoxical immune reconstitution inflammatory syndrome (TB-IRIS) after ART initiation, yet the optimal treatment of TB-IRIS is unknown. A recent randomized-controlled trial showed the benefit of prednisone over placebo in reduction of days of hospitalization and invasive procedures. The investigators hypothesize that nonsteroidal anti-inflammatory drugs (NSAIDs) are as effective as corticosteroids for treatment of non-life threatening TB-IRIS in HIV-infected patients and hypothesize that adjunctive treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (Statins) may improve the outcomes. This is a randomized controlled trial with a 2x2 factorial design to test the relative benefit of corticosteroids, NSAIDS, and Statins for the symptomatic and immunologic control of TB-IRIS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •HIV-1 infection documented by any locally licensed ELISA or rapid HIV test kit.
- •Age >18 years
- •Paradoxical TB-IRIS diagnosed by case definition (see section 5.2)
- •Ability and willingness of the participant or legal guardian/representative to give informed consent. Receiving appropriate ART and anti-TB therapy, as judged by the site investigator
排除标准
- •Inability to take oral medication;
- •Receiving chemotherapy, immunosuppressant, corticosteroid, NSAID, or statin medications; (ASA is acceptable)
- •Cannot or unlikely to attend regular clinic visits;
- •Known allergy to NSAIDs, statins or corticosteroids;
- •Liver transaminase > 2 times the upper limit of normal within 60 days of enrollment;
- •History of myositis/myopathy;
- •High Investigator Suspicion of anti-TB treatment failure due to TB-resistance or medication non-adherence;
- •Receiving ongoing azole anti-fungal for treatment or secondary prophylaxis of cryptococcosis, histoplasmosis or penicilliosis;
- •Serious co-morbidities, co-infections, or laboratory values who should not receive NSAIDs, steroid or statins, as judged by the site investigator;
- •Minimal IRIS reaction which is unlikely to require treatment, as judged by the site investigator;
- •Pregnancy (a negative urine pregnancy test at screening is required for women of childbearing potential) or breast feeding;
- •Receiving a HIV treatment regimen containing a protease inhibitor at study entry.
- •Exclusion for Randomization A Only
- •Life threatening TB-IRIS, as defined by:
- •Acute respiratory failure; PaO2 < 60 on room air or;
- •Altered mental status or;
- •New focal neurological deficit or;
- •Compression of the vital organs.
- •Persons with uncontrolled diabetes mellitus;
- •Impair kidney function, glomerular filtration rate <60 ml/min; within 72 hours of consent
- •Uncontrolled congestive heart failure
- •History of bleeding disorder;
- •Platelet count <100,000/µL;
- •History of significant gastrointestinal bleeding or ulceration;
- •Prior adjunctive corticosteroid therapy for this TB episode for > 48 hr;
- •Pregnancy
研究组 & 干预措施
Steroid+Statin
Experimental
- Dexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
- Atorvastatin: 80 mg once daily (equivalent to 30mg ± 10mg with rifamycin co-administration)
干预措施: Dexamethasone (Drug)
Steroid+Statin
Experimental
- Dexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
- Atorvastatin: 80 mg once daily (equivalent to 30mg ± 10mg with rifamycin co-administration)
干预措施: Atorvastatin (Drug)
NSAID+Statin
Active Comparator
- Naproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
- Atorvastatin: 80 mg once daily (equivalent to 30mg ± 10mg with rifamycin co-administration)
干预措施: Atorvastatin (Drug)
NSAID+Statin
Active Comparator
- Naproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
- Atorvastatin: 80 mg once daily (equivalent to 30mg ± 10mg with rifamycin co-administration)
干预措施: Naproxen (Drug)
Steroid+Placebo
Active Comparator
- Dexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
- Placebo
干预措施: Dexamethasone (Drug)
Steroid+Placebo
Active Comparator
- Dexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
- Placebo
干预措施: Placebo (Drug)
NSAID+Placebo
Active Comparator
- Naproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
- Placebo
干预措施: Naproxen (Drug)
NSAID+Placebo
Active Comparator
- Naproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
- Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Clinical Symptom Score at Day 7, as measured by the 10-point visual analog scale to quantify symptom severity.
时间窗: Day 7
Change in serum C-reactive protein at Day 7
时间窗: Day 7
次要结局
- CD4 count change(28 days)
- Days of hospitalization combined with outpatient therapeutic procedures(56 days)
- Study medicine discontinuation(28 days)
- Radiologic improvement at 2 weeks;(14 days)
- Karnofsky Performance Status Scale at day 7 and 28;(Day 7 and Day 28)
- Incidence of Adverse Events(56 days)
- Mortality(56 days)
- Recurrence of IRIS manifestations within the 8 week study period(56 days)
- ART or TB therapy discontinuation(56 days)
- Incidence of sputum acid fast bacilli (AFB) smear positivity at day 28(Day 28)
研究者
研究点 (3)
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