Randomized Non-inferiority Study Comparing a Strategy Maintaining Current Enfuvirtide-based Antiretroviral Therapy to a Strategy Replacing Enfuvirtide by an Integrase Inhibitor (Raltegravir) in HIV-1 Infected Subjects With Plasma Hiv-1 RNA Levels Below 400 Copies Per ml.ANRS 138 EASIER
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 170
- 试验地点
- 2
- 主要终点
- comparison of the proportions of virologic failure, defined as two consecutive pVL above 400 cp per ml, through 24 weeks in enfuvirtide-maintained arm versus raltegravir arm
研究概览
简要总结
Switching from enfuvirtide to raltegravir in the treatment of HIV-infected patients who sustain viral suppression with a combination therapy including enfuvirtide (or : with an enfuvirtide-based combination therapy)
详细描述
In patients who have failed under the three main classes of antiretroviral agents (NRTI, NNRTI and PI) and in whom the control of viral replication in the plasma has ultimately been achieved with enfuvirtide, the aim is to sustain this virological success for as long as possible to thus enable satisfactory immune reconstitution, avoid further accumulation of viral mutations conferring resistance to the drugs and protect the patient from the risk of opportunistic disease and death.
Indeed, enfuvirtide is the lead compound in the new class of antiretroviral drugs which inhibit the fusion of HIV-1 virus with its target cell. Its in vivo efficacy was demonstrated during the pivotal studies TORO 1 and 2. Despite its efficacy, maintaining long-term treatment with enfuvirtide is nonetheless difficult for patients because of the constraints related to twice-daily subcutaneous parenteral injections. Furthermore, these subcutaneous injections are associated with inflammatory reactions at the injection site in 98 per cent of patients, without any reduction in frequency or severity over time. It is thus critical for patients who are well controlled by enfuvirtide to be able to simplify their treatment by replacing enfuvirtide with another active compound taken by mouth, which would enable maintenance of the virological response and acceptable safety in patients who have usually failed under the three main classes of antiretroviral drugs. A new antiviral compound, viral integrase inhibitor called raltegravir, could be proposed instead of enfuvirtide.
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
- •Chronic HIV-1 infection
- •Treatment with a well-tolerated combination of antiretroviral drugs unchanged for at least 3 months, including enfuvirtide
- •Absence of any uncontrolled opportunistic disease
- •No restrictions on CD4 lymphocyte levels
- •Plasma HIV-1 RNA below 400 copies per ml for at least 3 months (at least two consecutive tests below 400 copies per ml prior to inclusion in the study, not including that on W -4)
- •For women of childbearing age, use of mechanical contraception during any sexual intercourse and negative pregnancy test (plasma ß HCG) at W -4
排除标准
- •HIV-2 infection
- •Plasma HIV-1 RNA levels above 400 copies/ml on one occasion during the 3 months prior to screening (or the pre-inclusion visit at W -4)
- •Poor compliance with antiretroviral therapy current at W -4
- •Current treatment with an investigational drug (except cohort ATU)
- •Patient previously treated with an integrase inhibitor in the context of a clinical study
- •Woman who is pregnant or likely to become so, is breastfeeding or refuses to use contraception
- •Multiple drug therapy ongoing or necessary in the foreseeable future for Kaposi's disease or lymphoma
- •Treatment with interferon ongoing or necessary in the foreseeable future for chronic hepatitis B or C
- •Acute hepatitis whatever the case, or decompensated cirrhosis
- •Current treatment with interferon, interleukin or anti-HIV vaccine
- •Any condition (including, but not limited to, the consumption of alcohol or drugs) which might, in the investigator's opinion, compromise the safety of treatment and/or patient compliance with the protocol
- •Significant biological abnormalities (hemoglobin below 8g per dl, polynuclear neutrophils below 750 per mm3, platelets below 50,000 per mm3, serum creatinine above 3 times the level deemed normal by the laboratory (N), ASAT or ALAT above 5N, serum lipase above 2N) and total bilirubin above 2N (except if the patient is receiving atazanavir or indinavir)
- •Concomitant treatments including one or more compounds interacting with UGT1A1
- •anti-infective agents: rifampicin/rifampin
- •psychotropic/anti-epileptic drugs: phenytoin, phenobarbital.
研究组 & 干预措施
Intensification arm
emtricitabine/TDF + efavirenz or lopinavir/ritonavir + enfuvirtide
干预措施: FTC/TDF + EFV or LPV/R +T20 (Drug)
Standard arm
emtricitabine/TDF + efavirenz or lopinavir/ritonavir
干预措施: FTC/TDF + EFV or LPV/R (Drug)
结局指标
主要结局
comparison of the proportions of virologic failure, defined as two consecutive pVL above 400 cp per ml, through 24 weeks in enfuvirtide-maintained arm versus raltegravir arm
时间窗: W24
次要结局
- quality of life and adherence(W4, W12, W24 and W48)
- morphological and metabolic disorders outcome(between W0 & W48)
- comparison of time to onset of virologic failure(W24 and W48)
- proportions of pts with pVL under 50 and 400 cp per ml respectively at week 24 and week 48 ;(W24 & W48)
- plasma viral mutations in the event of virologic failure, compared to HIV-DNA archived mutations at baseline;(virologic failure)
- change in CD4 levels(between W0 and W48)
- incidence of HIV-related events(between W0 and W48)
- drug plasma and male genital tract pharmacokinetics;(W24 & W48)
- incidence and type of adverse events, including adverse reactions(between W0 & W48)
- proportions of discontinuing allocated treatment strategy(between W0 & W48)