Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints

• Status: Completed
• Trial end date: 2018-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kirby Institute
• Collaborators: Merck Sharp & Dohme Corp.; National Institute of Allergy and Infectious Diseases (NIAID); University of Melbourne; University of Minnesota; University of Minnesota - Clinical and Translational Science Institute
• Treatments: Vorapaxar

Criteria

Inclusion Criteria:

1. HIV-1 positive by licensed diagnostic test

2. aged ≥40 years

3. plasma HIV RNA <50 copies/mL for at least 24 weeks

4. screening CD4+ cell count > 50 cells/mm3

5. 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)

6. 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)

7. provision of written informed consent

Exclusion Criteria:

1. Absolute neutrophil count (ANC) <1000 cells/μL

2. hemoglobin <10.0 g/dL

3. platelet count <75,000 cells/μL

4. AST and/or ALT >2.5 x ULN

5. estimated glomerular filtration rate <30mL/min/1.73m2 ) using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation

6. history of myocardial infarction or unstable atherosclerotic disease

7. history of ischemic stroke or transient ischaemic attack (TIA)

8. active peptic/duodenal ulcer or other bleeding disorder within the previous 12 months

9. intent to have surgery within the 6 month period after randomisation

10. current use of aspirin or P2Y12 antiplatelet therapy

11. 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.

12. participants unlikely to be able to remain in follow-up

13. pregnant or nursing mothers

14. 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.