CSP #512 - Options in Management With Anti-Retrovirals (OPTIMA), Management of Patients With HIV Infection for Whom First and Second-line Highly Active Anti-Retroviral Therapy Has Failed
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 368
- 试验地点
- 30
- 主要终点
- Number of Participants With New or Recurrent AIDS Event, or Death
研究概览
简要总结
This 'pragmatic' trial is a 2X2 open randomized study of patients in advanced HIV disease who have failed on conventional Highly Active Antiretroviral Therapy (HAART) regimens including all three classes of anti-HIV drugs. The first randomization will allocate patients to an intended 3-month antiretroviral drug-free period (ARDFP) or No ARDFP. The second randomization will allocate patients to Mega-ART (5+ drugs) or to Standard-ART (up to 4 drugs). The total study duration is 6.5 years with 5 years of intake and 1.5 year (minimum) of follow-up; median duration of patient follow-up is about 4 years. The target sample size is 390 patients and will provide 75% power to detect a 30% reduction in the hazard rate for the primary endpoint with mega-ART. Sixty-four sites will be participating in the trial--24 VA, 19 UK and 21 Canada.
详细描述
Primary Hypothesis:
Compared to patients in Standard Antiretroviral Therapy (ART), patients in Mega-ART assuming full compliance, will experience a 30% reduction in the hazard of reaching a clinical endpoint (AIDS event or death).
Secondary Hypotheses:
Time to development of a new, non-HIV related serious adverse event, health related quality of life, the incidence of grade 3 or 4 clinical or laboratory adverse events and changes in virological and immunological markers (CD4 cell count, viral load, resistance profiles) will vary between the different treatment strategies.
Interventions:
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
- 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
- •Ability to provide informed consent
- •Age of 18 years or more
- •Serologic or virologic diagnosis of HIV infection
- •Failure of at least two different multi-drug regimens that include drugs of all 3 classes that the patient can tolerate or laboratory evidence of resistance to drugs in each of the 3 classes
- •Had at least 3 months of current ART and are still on treatment
- •Two most recent results (which can include screening) on current ART of CD4 count less than or equal to 300 cells/mm3 or less than or equal to 15%, and a plasma viral load greater than or equal to 5,000 copies/ml (Roche Amplicor, v1.0), or greater than or equal to 2,500 copies/ml (by bDNA: Bayer v3.0/Chiron v3.0 or PCR:Roche Amplicor Monitor/COBAS v1.5)
排除标准
- •Pregnancy, breast-feeding or planned pregnancy
- •Likelihood of poor protocol follow-up or if Mega-Art is not feasible (due to significant intolerance of many ARV drugs)
- •Serious, uncontrolled major opportunistic infection (OI) within 14 days of screening
- •Likelihood of early death due to non-HIV disease
研究组 & 干预措施
No ARDFP+Standard-ART
No Antiretroviral Drug-Free Period (No ARDFP) and Standard-ART
干预措施: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP (Other)
No ARDFP+Standard-ART
No Antiretroviral Drug-Free Period (No ARDFP) and Standard-ART
干预措施: Standard ART vs Mega ART (Drug)
No ARDFP+Mega-ART
No Antiretroviral Drug-Free Period (No ARDFP) and Mega-ART
干预措施: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP (Other)
No ARDFP+Mega-ART
No Antiretroviral Drug-Free Period (No ARDFP) and Mega-ART
干预措施: Standard ART vs Mega ART (Drug)
ARDFP+Standard-ART
Antiretroviral Drug-Free Period (ARDFP) and Standard-ART
干预措施: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP (Other)
ARDFP+Standard-ART
Antiretroviral Drug-Free Period (ARDFP) and Standard-ART
干预措施: Standard ART vs Mega ART (Drug)
ARDFP+Mega-ART
Antiretroviral Drug-Free Period (ARDFP) and Mega-ART
干预措施: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP (Other)
ARDFP+Mega-ART
Antiretroviral Drug-Free Period (ARDFP) and Mega-ART
干预措施: Standard ART vs Mega ART (Drug)
结局指标
主要结局
Number of Participants With New or Recurrent AIDS Event, or Death
时间窗: From date of randomization until onset of primary outcome or end of study follow-up (12/31/2007) whichever occured first, up to 6.5 years
New or recurrent AIDS event or Death were compared between No ARDFP (continuation)+Standard-ART (standard), No ARDFP (continuation)+Mega-ART (intensification), ARDFP (interruption)+Standard-ART (standard) and ARDFP (interruption)+Mega-ART (intensification)
次要结局
- Number of Participants With a New, Non-HIV Related Serious Adverse Event(From date of randomization until onset of secondary outcome or end of study follow-up (12/31/2007) whichever occured first, up to 6.5 years)
- Number of Participants With New, Non-HIV Related Serious Adverse Event(From date of randomization until onset of secondary outcome or end of study follow-up (12/31/2007) whichever occured first, up to 6.5 years)