A Randomised, Open-label Trial to Assess the Safety and Efficacy of Switching to Tenofovir-emtricitabine or Abacavir-lamivudine: The STEAL Study.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 357
- 试验地点
- 31
- 主要终点
- virological failure defined by HIV RNA>400copies/mL plasma on 2 consecutive occasions ³4 wks apart(Roche Amplicor v1.5, LLD 50 copies/mL)
研究概览
简要总结
Combination antiretroviral therapy for the treatment of HIV has a high pill burden. Two dual-tablets, abacavir-lamivudine and tenofovir-emtricitabine, are now licensed in the United States and will be available in Australia in December 2005. Data available suggest that the potency of these tablets are similar in controlling replication of the HIV virus, but not have not been directly compared in regard to clinically significant toxicities. We therefore aim to compare the overall safety and efficacy of the two dual-tablets over a 2 year period in HIV infected adults. We hypothesise that the two dual-NRTI treatments will be similar in efficacy and safety.
详细描述
The aim of this study is to compare the overall safety and efficacy of two dual-NRTI, once daily, tablets over a 2 year period in HIV infected adults.
The study is a randomised, multi-centre, 2 year study of two dual NRTI, once daily tablets in subjects with HIV, currently taking two individual NRTIs as part of their therapy. 350 subjects will be randomised in a 1:1 ratio to either:
- tenofovir (TDF) 300mg + emtricitabine (FTC) 200mg OR
- abacavir (ABC) 600mg + lamivudine (3TC) 300mg. Subjects will cease their current individual NRTI treatment, commence their randomised dual NRTI tablet, and continue on their current NNRTI or PI therapy.
Subjects will be stratified by the type of NRTI they are currently taking (ABC, TDF or other); whether they are currently taking a protease inhibitor (yes or no); and by the site where they are randomised. A study plan is enclosed
Subjects will be closely monitored (at 1 month and then every 3 months until week 96) for safety by evaluating the incidence and severity of adverse effects/abnormal laboratory parameters. Study investigations enclosed. It is optional whether subjects also provide plasma, serum and cells (PBMCs) for storage. These samples will be available for analysis for sub-studies agreed to through the IVRN expression of interest network.
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
- •documented HIV infection
- •age at least 18 years
- •stable (≥ to 12 weeks) ART including at least two NRTIs, currently well tolerated, with no plan to change any other component of the ART regimen at or after baseline
- •HIV RNA < 50 copies/mL plasma for the preceding 12 weeks
- •GFR ≥ 70 mL/min/1.73m2 (estimated by the abbreviated MDRD equation23 estimated GFR = 186 x ([SCR/88.4]-1.154) x age-0.203 x (0.742 if female) x (1.210 if African-American)
- •provision of written, informed consent
排除标准
- •HLA-B*5701 positive at screening OR evidence of previous ABC hypersensitivity OR clinical failure in participants taking abacavir for at least 30 days
- •current therapy comprising triple NRTI therapy alone
- •current use of ABC/3TC FDC (Kivexa) or TDF/FTC FDC (Truvada)
- •history of non-traumatic osteoporotic fracture
- •prior hypersensitivity or intolerance to ABC, 3TC, TDF or FTC
- •prior clinical failure to a regimen containing ABC or TDF
- •prior use of TDF for control of previously active hepatitis B (HBsAg+ or HBV DNA+) in patients likely to be resistant to 3TC/FTC
- •current therapy including unboosted atazanavir
- •concurrent use of aminoglycosides, IV amphotericin B, cidofovir, cisplatin, foscarnet, IV pentamidine, probenecid, adefovir or immunomodulatory agents
- •clinical evidence of cirrhosis (e.g. smooth liver, no features of portal hypertension)
- •creatinine clearance < 50 mL/min (estimated by the Cockcroft-Gault equation)18,19
- •Male: (140 - age in years) x (wt in kg) = CLCr (mL/min) 0.814 x (serum creatinine in µmol/L)
- •Female:(140 - age in years) x (wt in kg) x 0.85 = CLCr (mL/min) 0.814 x (serum creatinine in µmol/L)
研究组 & 干预措施
1
Abacavir 600mg/Lamivudine 300mg
干预措施: Abacavir 600mg - Lamivudine 300mg (Drug)
2
Tenofovir 300mg/emtricitabine 200mg
干预措施: Emtricitabine 200mg - Tenofovir 300mg (Drug)
结局指标
主要结局
virological failure defined by HIV RNA>400copies/mL plasma on 2 consecutive occasions ³4 wks apart(Roche Amplicor v1.5, LLD 50 copies/mL)
时间窗: Week 48
次要结局
- plasma HIV RNA<50copies/mL; time to virological failure (VF); virological resistance in those with VF; all SAEs; use of concomitant meds for toxicity; adherence; QoL; CD4+lymphocyte count; full blood count; biochemistry; lipid parameters(Week 48 and 96)
- glycaemic parameters; DEXA parameters; resolution of AEs; progression to AIDS; death; discontinuation of ART.(Week 48 and 96)