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

NCT02394730 | Completed Phase 1 Results DMC

• 2 other identifiers: 2014-01-ADVAI000585-26-288416
• Study Type: interventional
• Target: 65
• Locations: 2 countries
• Sites: 7

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.

Conditions

HIV

Keywords

HIV, d-dimer, hs-CRP, activated T-lymphocytes

Outcome Measures

Primary Outcomes (1)

• Mean Percent Change From Baseline for D-dimer (ng/mL) to the Average of Weeks 8 and 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.

  at week 8 and week 12

Secondary Outcomes (14)

• Number of Participants in Each Treatment Group With Plasma HIV-1 RNA <50 Copies/mL

  at week 18

• 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

Study Arms (2)

vorapaxar

EXPERIMENTAL

2.5mg of vorapaxar po qd

Drug: vorapaxar

Placebo

PLACEBO COMPARATOR

sugar pill po qd

Drug: Placebo

Interventions

vorapaxar DRUG

2.5mg of vorapaxar taken orally once daily for 12 weeks

Also known as: Zontivity

vorapaxar

Placebo DRUG

Sugar pill taken orally once daily for 12 weeks

Also known as: sugar pill

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kirby Institute: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• University of Minnesota: collaborator
• University of Melbourne: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (7)

Georgetown University Hospital

Georgetown, Maryland, 20007, United States

Location

Hennepin County Medical Centre

Minneapolis, Minnesota, 55415, United States

Location

St Vincent's Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Taylor Square Private Clinic

Darlinghurst, New South Wales, 2010, Australia

Location

Melbourne Sexual Health Centre

Carlton, Victoria, 3053, Australia

Location

Northside Clinic

Fitzroy North, Victoria, 3068, Australia

Location

Monash Medical Centre

Melbourne, Victoria, 3168, Australia

Location

Related Publications (1)

• 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.

  PMID: 30257802 DERIVED

MeSH Terms

Interventions

vorapaxar; Sugars

Intervention Hierarchy (Ancestors)

Carbohydrates

Results Point of Contact

• Title: Sean Emery, Chief Principal Investigator
• Organization: University of New South Wales

s.emery@unsw.edu.au

+61 2 9385 0897

Study Officials

• Sean Emery

  University of NSW, Kirby Institute

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2015
• First Posted: March 20, 2015
• Study Start: September 1, 2015
• Primary Completion: November 1, 2017
• Study Completion: January 1, 2018
• Last Updated: March 6, 2019
• Results First Posted: February 28, 2019

Record last verified: 2019-03

Locations

AU (5); US (2)