A Double Blind Randomised Comparison of Vorapaxar Versus Placebo for the Treatment of HIV Associated Inflammation and Coagulopathy in Patients With Well Controlled HIV Replication
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 7
- 主要终点
- Mean Percent Change From Baseline for D-dimer (ng/mL) to the Average of Weeks 8 and 12
研究概览
简要总结
ADVICE is a randomised, international, double-blind, placebo-controlled trial. The purpose of the ADVICE study is to compare the safety and efficacy of vorapaxar in reducing d-dimer expression and markers of cellular immune activation over a period of 12 weeks among people with HIV infection who are successfully treated with combination antiretroviral therapy containing an HIV integrase inhibitor. A secondary objective of the study will be to demonstrate that following cessation of vorapaxar in patients with well controlled HIV replication there will be an increase in the levels of d-dimer over a 6 week period. 60 participants from 4 clinical sites in Australia and the USA will be recruited and followed for a minimum of 18 weeks.
详细描述
Consenting participants will be screened and within 14 days randomly allocated to receive either vorapaxar (2.5mg) or matched placebo once daily for 12 weeks (phase 1). Participants will be seen one week after randomisation and then at weeks 4, 8 and 12 (phase 1). At the week 12 visit, patients will not be dispensed any study treatment. In phase 2 all study treatment will stop for 6 weeks. At week 18 patients will be seen for a final study visit.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-1 positive by licensed diagnostic test
- •aged ≥40 years
- •plasma HIV RNA <50 copies/mL for at least 24 weeks
- •screening CD4+ cell count > 50 cells/mm3
- •treated for at least 12 weeks with a suppressive regimen of combination antiretroviral therapy that does not include HIV protease inhibitors and/or NNRTIs (except rilpivirine)
- •plasma d-dimer >200ng/mL (>0.2μg/mL or >0.2mg/L) fibrinogen equivalent units or >100ng/mL (>0.1 μg/mL or >0.1mg/L) d-dimer units in the absence of established cause (deep vein thrombosis/embolism)
- •provision of written informed consent
排除标准
- •Absolute neutrophil count (ANC) <1000 cells/μL
- •hemoglobin <10.0 g/dL
- •platelet count <75,000 cells/μL
- •AST and/or ALT >2.5 x ULN
- •estimated glomerular filtration rate <30mL/min/1.73m2 ) using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation
- •history of myocardial infarction or unstable atherosclerotic disease
- •history of ischemic stroke or transient ischaemic attack (TIA)
- •active peptic/duodenal ulcer or other bleeding disorder within the previous 12 months
- •intent to have surgery within the 6 month period after randomisation
- •current use of aspirin or P2Y12 antiplatelet therapy
- •use of anticoagulants, (eg. heparin or warfarin), fibrinolytic therapy, chronic use (more than 5 consecutive days) of nonsteroidal anti-inflammatory drugs (NSAIDS), strong CYP3A4 inhibitors or inducers. See Manual of Operations for full list of medications to avoid.
- •participants unlikely to be able to remain in follow-up
- •pregnant or nursing mothers
- •in the clinical judgement of the investigator, participation in this trial is deemed inappropriate as this may conflict with the well-being of the participant.
研究组 & 干预措施
vorapaxar
2.5mg of vorapaxar po qd
干预措施: vorapaxar (Drug)
Placebo
sugar pill po qd
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Percent Change From Baseline for D-dimer (ng/mL) to the Average of Weeks 8 and 12
时间窗: at week 8 and week 12
Mean of week 8 and week 12 minus week 0 (on log10 scale) then back transforming the log10 difference to obtain percentage change from baseline.
次要结局
- Mean Change From Baseline to Week 12 in CD4+ Cell Counts(at week 12)
- Mean Change From Baseline to Week 12 in CD8+ Cell Counts(at week 12)
- Number of Patients in Each Treatment Group With D-dimer <165ng/mL at Week 12(week 12)
- Number of Patients in Each Treatment Group With D-dimer > or Equal to 165ng/mL at Week 18(week 18)
- Mean Change From Baseline in log10 D-Dimer(at week 18)
- Percent Change From Baseline Hs-CRP (ug/mL) to the Average of Week 8 and Week 12(week 8 and 12)
- Mean Percent Change From Baseline IL-6 (pg/mL) to the Average of Week 8 and Week 12(at week 8 and week 12)
- Changes From Baseline in Renal Function Measured by the CKD-EPI Estimate of Creatinine Clearance at Week 12(at week 12)
- Number of Participants in Each Treatment Group With Plasma HIV-1 RNA <50 Copies/mL(at week 18)
- Mean Change From Baseline in log10 Hs-CRP at Week 18(at week 18)
- Differences Between Treatment Groups in Mean Change From Baseline log10 IL-6(at week 18)
- Total Number of Participants With BARC Type 1, 2, 3, 4, or 5 Bleeding Episodes(at week 18)
- Total Number of Participants With Any SAE Between Baseline and Week 18(week 18)
- Total Number of Participants With Any AE Between Baseline to Week 18(week 18)