Phase III Open-label Randomized Multicenter Trial to Assess the Non-inferiority of Raltegravir Compared With EFavirenz, Both in Combination With LAmivudine and TEnofovir, in ART-naïve HIV-1-infected Patients Receiving Rifampin for Active TuBerculosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 460
- 试验地点
- 5
- 主要终点
- Proportion of patients in virologic success
研究概览
简要总结
Phase III trial evaluating raltegravir as an alternative to efavirenz for antiretroviral treatment of HIV-infected patients with tuberculosis.
详细描述
Phase III multicenter, international, open-label, randomized trial evaluating non-inferiority of raltegravir at dose of 400mg BID compared to efavirenz 600mg QD, both in association with tenofovir disoproxil fumarate and lamivudine in ART-naïve HIV-1 infected patients with active TB disease receiving a rifampin-based TB treatment initiated <8 weeks before inclusion. Patients will be randomized between 2 arms: the raltegravir (RAL) 400 mg bid arm or the efavirenz (EFV) 600 mg qd arm, each in combination with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) and will be followed for 48 weeks after entry in the trial (ART initiation).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent form
- •Aged 18 years or more
- •Confirmed HIV-1 infection as documented at any time prior to trial entry per national HIV testing procedures
- •ART naïve
- •For women of childbearing potential i.e. women of childbearing age who are not menopausal, or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy) or not refraining from sexual activity: negative urinary test for pregnancy and acceptance to use contraceptive methods
- •Confirmed or probable active TB disease of any location, except neurological (meningitis or encephalitis), according to the following criteria based on WHO updated definitions:
- •Bacteriologically confirmed pulmonary TB (PTB) or extrapulmonary TB (EPTB), e.g. TB with a biological specimen positive by smear microscopy, culture or nucleic acid amplification test (such as Xpert MTB/RIF).
- •Clinically diagnosed PTB or EPTB with typical histological evidence of TB (caseous or granulomatous) on biopsy specimen or positive urinary LAM test OR a significant improvement on TB treatment
- •Ongoing standard rifampin-containing TB treatment for ≤8 weeks at inclusion
- •For French patients, affiliation to a Social Security program
排除标准
- •HIV-2 co-infection
- •Impaired hepatic function (icterus or ALT (SGPT) > 5ULN)
- •Hemoglobin < 6.5 g/dl
- •Creatinine clearance <60ml/min (assessed by the Cockroft and Gault formula)
- •Mycobacterium tuberculosis strain resistant to rifampin (current or past history).
- •Neurological TB (meningitis or encephalitis)
- •Severe associated diseases requiring specific treatment (including all specific AIDS defining illnesses other than TB, and any severe sepsis)
- •Any condition which might, in the investigator's opinion, compromise the safety of treatment and/or patient's adherence to trial procedures including very severe TB-related clinical condition
- •Concomitant treatments including phenytoin or phenobarbital (compounds interacting with UGT1A1)
- •For HCV co-infected patients, need to start specific treatment for hepatitis during the trial duration
- •For women of childbearing potential:
- •Pregnancy or breastfeeding
- •Refusal to use a contraceptive method
- •Any history of ARV intake for prevention of mother to child transmission of HIV (pMTCT)
- •Subjects participating in another clinical trial evaluating therapies and including an exclusion period that is still in force during the screening phase
- •Person under guardianship, or deprived of freedom by a judicial or administrative decision
研究组 & 干预措施
Raltegravir
Tenofovir 300mg QD + lamivudine 300mg QD + raltegravir 400mg BID
干预措施: Tenofovir + lamivudine + raltegravir (Drug)
Efavirenz
Tenofovir 300mg QD + lamivudine 300mg QD + efavirenz 600mg QD
干预措施: Tenofovir + lamivudine + efavirenz (Drug)
结局指标
主要结局
Proportion of patients in virologic success
时间窗: Week 48
Virologic success, defined as plasma HIV-1 RNA \<50 copies/mL, at week 48 with a window period of 42 to 54 weeks (snapshot algorithm). Discontinuation of the strategy (ie. permanent discontinuation of EFV, RAL), missing values, loss to follow-up and death will be considered as failure.
次要结局
- Frequency, type and time to new or recurrent AIDS-defining illnesses(Week 48)
- Change in plasma HIV-1 RNA from baseline to week 48(Week 48)
- Frequency and time to new antiretroviral genotypic resistance in plasma RNA in patients with virologic failure(Week 48)
- Time to death(Week 48)
- Frequency, type and time to grade 3 or 4 adverse events(Week 48)
- Time to virologic failure during follow-up(Week 48)
- Change in CD4 cell counts from baseline to week 48(Week 48)
- Frequency, type and time to Immune Reconstitution Inflammatory Syndrome(Week 48)
- Frequency, type and time to drug-induced clinical or biological adverse reactions of grade 3 or 4 or leading to treatment interruption(Week 48)
- Frequency, type and time to severe HIV-associated non-AIDS defining illnesses(Week 48)
- Proportion of patients in virologic success at each time point (HIV-1 RNA<50 copies/mL)(Week 48)
- Frequency of tuberculosis treatment outcomes(Week 48)