A Prospective, Open-label Trial of Two Abacavir/Lamivudine Based Regimen (ABC/3TC + Darunavir/Ritonavir or ABC/3TC + Raltegravir) in Late Presenter naïve Patients (With CD4 Count <200 Cells/µL - Advanced HIV Disease)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- HIV RNA Viral Load
研究概览
简要总结
- PROTOCOL SUMMARY This is a prospective, randomized open-label, 2 arm, 3-phase trial to compare the 48-weeks virological response of two different regimens containing abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.
1.1 Clinical Objectives: Primary Objective: To compare the 48-week virological response to two different regimens containing abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.
Secondary Objective: a) To compare immunological response at 48 weeks; b) To determine the safety and tolerability of the 2 regimens.
1.2 Study population: 350 in/out patients 1.3 Outcome Primary Endpoint
- Proportion of patients with HIV RNA<50 copies/mL after 48 weeks Secondary Endpoints(s)
- Change in CD4+ cell count from baseline through week 48
- Time to virological rebound 1.4 Study design: Multicentre, parallel group, randomised, open label, non-inferiority study 1.5 Treatment regimens: Arm A: abacavir/lamivudine 1 tablet once a day + raltegravir 400 mg (1 tablet twice a day) Arm B: abacavir/lamivudine 1 tablet once a day + ritonavir 100 mg + darunavir 800 mg once a day.
All drugs have been approved for the treatment of HIV infection. The study population will consist of 350 HIV-positive, HLA B5701-negative patients. At baseline, patients will be randomized 1:1 to start abacavir/lamivudine plus either raltegravir or darunavir/ritonavir. Randomization will be stratified on the basis of the screening CD4+ cell count (≤100 vs ≥100 cells/µL), to ensure balance across treatments groups 1.7 Criteria for Safety: Adverse events and laboratory assessments. 1.8 Statistical analysis: As this is a non-inferiority trial, we will calculate the difference in the proportions of patients experiencing the primary outcome in the two treatment arms and will calculate a 95% confidence interval for this. Non-inferiority of the raltegravir arm will be demonstrated if the lower limit of the 95% confidence interval is greater than -12%. In case non-inferiority will be met, analyses for superiority will be performed.
详细描述
- PROTOCOL SUMMARY This is a prospective, randomized open-label, 2 arm, 3-phase trial to compare the 48-weeks virological response of two different regimens containing abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.
1.1 Clinical Objectives: Primary Objective: To compare the 48-week virological response to two different regimens containing abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.
Secondary Objective:
- To compare immunological response at 48 weeks;
- To determine the safety and tolerability of the 2 regimens. 1.2 Study population: 350 inpatients or outpatients will be randomized 1.3 Outcome Primary Endpoint
- Proportion of patients with undetectable viremia (HIV RNA<50 copies/mL) after 48 weeks Secondary Endpoints(s)
- Change in CD4+ cell count from baseline through week 48
- Time to virological rebound Safety endpoints
- Incidence of adverse events (AEs)
- Incidence of serious adverse events (SAEs)
- Discontinuations due to adverse events
- Incidence of grade 3 or 4 laboratory abnormalities. 1.4 Study design Multicentre, parallel group, randomised, open label, non-inferiority study 1.5 Planned sample size: The planned sample size for this trial is 350 patients 1.6 Treatment regimens: Arm A: abacavir/lamivudine 1 tablet once a day + raltegravir 400 mg (1 tablet twice a day) Arm B: abacavir/lamivudine 1 tablet once a day + ritonavir 100 mg + darunavir 800 mg once a day.
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 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females (inpatients or outpatients) aged 18-64 years who are HIV-1 antibody seropositive, with a CD4 count <200 cells/uL.
- •All patients should be antiretroviral-naive
- •All patients should be HLA B57 or HLA B5701 negative
- •Patients must have an HIV RNA level <500,000 copies/mL
- •Patients with an active opportunistic infection could be enrolled as long as this was diagnosed more than 2 weeks prior to screening.
- •Patients must meet the following laboratory criteria. Neutrophil count > 1,000 cells/mm3 Haemoglobin > 9.0 grams/dl (men and women) Platelet count ≥ 75,000 cells/mm3 Alkaline phosphatase < 3.0 the upper limit of normal ALT and AST < 3.9 times the upper limit of normal Total bilirubin < 1.5 times the upper limit of normal.
- •Female patients of childbearing potential must be willing to use a reliable form of contraception, which will include a medically approved form of barrier contraception.
- •Patients must be able to provide written consent to comply with study requirements.
排除标准
- •Patients with genotypic mutations for any of the study drugs.
- •Patients with an opportunistic infection diagnosed in the 2 weeks prior to screening.
- •Female patients who are pregnant or breastfeeding.
- •Patients who are receiving any investigational drug or anti-neoplastic radiotherapy/chemotherapy other than local skin radiotherapy within 12 weeks before randomization.
- •Patients with a current history of intravenous drug abuse, alcohol or substance abuse.
研究组 & 干预措施
abacavir/lamivudine + raltegravir
abacavir/lamivudine + raltegravir
干预措施: abacavir/lamivudine + raltegravir (Drug)
ABC/3TC + DRV/r
abacavir/lamivudine + darunavir/ritonavir
干预措施: abacavir/lamivudine + darunavir/ritonavir (Drug)
结局指标
主要结局
HIV RNA Viral Load
时间窗: baseline and week 48
The proportion of patients attaining an HIV RNA level \<50 copies/mL after 48 weeks will be the primary outcome.
次要结局
未报告次要终点
研究者
Cristina Mussini
Professor
University of Modena and Reggio Emilia