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

Kirby Institute

Status and phase: Completed; Phase 2; Phase 1

Conditions: HIV

Treatments: Drug: Placebo; Drug: vorapaxar

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT02394730

2014-01-ADV

AI000585-26-288416 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 65 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

65 participants in 2 patient groups, including a placebo group

vorapaxar

Experimental group

Description:

2.5mg of vorapaxar po qd

Treatment:

Drug: vorapaxar

Placebo

Placebo Comparator group

Description:

sugar pill po qd

Treatment:

Drug: Placebo