Phase 2
Completed N=65
Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints
Source: ClinicalTrials.gov NCT02394730 ↗Enrolled (actual)
65
Serious AEs
6.3%
Results posted
Feb 2019
Primary outcomePrimary: Mean Percent Change From Baseline for D-dimer (ng/mL) to the Average of Weeks 8 and 12 — -10.8; -8.5 percent
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Percent Change From Baseline for D-dimer (ng/mL) to the Average of Weeks 8 and 12 |
-10.8; -8.5 | — |
| SECONDARY Number of Participants in Each Treatment Group With Plasma HIV-1 RNA <50 Copies/mL |
31; 29 | — |
| SECONDARY Mean Change From Baseline to Week 12 in CD4+ Cell Counts |
-21.3; -29.7 | — |
| SECONDARY Mean Change From Baseline to Week 12 in CD8+ Cell Counts |
3; 81.1 | — |
| SECONDARY Number of Patients in Each Treatment Group With D-dimer <165ng/mL at Week 12 |
1; 2 | — |
| SECONDARY Number of Patients in Each Treatment Group With D-dimer > or Equal to 165ng/mL at Week 18 |
32; 29 | — |
| SECONDARY Mean Change From Baseline in log10 D-Dimer |
-2.21; -14.1 | — |
| SECONDARY Mean Change From Baseline in log10 Hs-CRP at Week 18 |
-0.03; -0.10 | — |
| SECONDARY Percent Change From Baseline Hs-CRP (ug/mL) to the Average of Week 8 and Week 12 |
-0.02; -15.7 | — |
| SECONDARY Mean Percent Change From Baseline IL-6 (pg/mL) to the Average of Week 8 and Week 12 |
12.6; -11.6 | — |
| SECONDARY Differences Between Treatment Groups in Mean Change From Baseline log10 IL-6 |
0.03; -0.10 | — |
| SECONDARY Total Number of Participants With BARC Type 1, 2, 3, 4, or 5 Bleeding Episodes |
12; 10 | — |
| SECONDARY Total Number of Participants With Any SAE Between Baseline and Week 18 |
3; 2 | — |
| SECONDARY Total Number of Participants With Any AE Between Baseline to Week 18 |
28; 28 | — |
| SECONDARY Changes From Baseline in Renal Function Measured by the CKD-EPI Estimate of Creatinine Clearance at Week 12 |
2.08; 2.05 | — |
Eligibility Criteria
Inclusion Criteria
- HIV-1 positive by licensed diagnostic test
- aged ≥40 years
- plasma HIV RNA 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
Exclusion Criteria
- Absolute neutrophil count (ANC) 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.
Data sourced from ClinicalTrials.gov (NCT02394730). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.