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

NCT ID: NCT02394730

Last Updated: 2019-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2018-01-31

Brief 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.

Detailed 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.

Conditions

HIV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

vorapaxar

2.5mg of vorapaxar po qd

Group Type: EXPERIMENTAL

vorapaxar

Intervention Type: DRUG

2.5mg of vorapaxar taken orally once daily for 12 weeks

Placebo

sugar pill po qd

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sugar pill taken orally once daily for 12 weeks

Interventions

vorapaxar

2.5mg of vorapaxar taken orally once daily for 12 weeks

Intervention Type: DRUG

Placebo

Sugar pill taken orally once daily for 12 weeks

Intervention Type: DRUG

Other Intervention Names

Zontivity; sugar pill

Eligibility 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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: collaborator

University of Melbourne

OTHER

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Kirby Institute

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sean Emery

Role: STUDY_DIRECTOR

University of NSW, Kirby Institute

Locations

Georgetown University Hospital

Georgetown, Maryland, United States

Hennepin County Medical Centre

Minneapolis, Minnesota, United States

St Vincent's Hospital

Darlinghurst, New South Wales, Australia

Taylor Square Private Clinic

Darlinghurst, New South Wales, Australia

Melbourne Sexual Health Centre

Carlton, Victoria, Australia

Northside Clinic

Fitzroy North, Victoria, Australia

Monash Medical Centre

Melbourne, Victoria, Australia

Countries

United States; Australia

References

ADVICE study group. Vorapaxar for HIV-associated inflammation and coagulopathy (ADVICE): a randomised, double-blind, placebo-controlled trial. Lancet HIV. 2018 Oct;5(10):e553-e559. doi: 10.1016/S2352-3018(18)30214-5. Epub 2018 Sep 23.

Reference Type: DERIVED

PMID: 30257802 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AI000585-26-288416

Identifier Type: OTHER

Identifier Source: secondary_id

2014-01-ADV

Identifier Type: -

Identifier Source: org_study_id