ADVICE Study - Attenuation of D-dimer using Vorapaxar to target Inflammatory and Coagulation Endpoints

Date Commenced:
November 2015
Project Status
Ongoing
Expected Date of Completion:
Ongoing
Project Supporters

National Health & Medical Research Council of Australia (NHMRC)

Merck Research Laboratories

Currently recruiting
Yes
image - ADVICE 284x284

About the Project

ADVICE is a double blind randomised comparison of vorapaxar versus placebo for the treatment of HIV associated inflammation and coagulopathy in patients with well controlled HIV replication. Vorapaxar (Zontivity™) is an oral competitive PAR-1 antagonist that inhibits thrombin-induced platelet aggregation.

Rationale

Elevated expression of d-dimer (corresponding to coagulopathy) and hs-CRP/IL-6 (corresponding to immune activation/inflammation) are associated with increased risk of death and serious end-organ diseases among people with HIV infection. While increased levels of these markers are driven by HIV replication, it is clear that even among people with well controlled HIV replication there is a consistent relationship between higher d-dimer levels and poorer clinical outcome. While combination antiretroviral therapy (cART) reduces levels of d-dimer, it does not result in normalisation. Even among patients with suppressed HIV RNA replication, expression of these markers is higher among people with HIV infection than those observed in age matched populations without HIV infection. Interventions to reduce either hypercoagulopathy and/or immune activation may permit a clearer understanding of the pathogenesis that underpins this presentation.

Aims

1.      To compare the safety and efficacy of vorapaxar versus placebo 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 either raltegravir or dolutegravir.

2.      A secondary objective of the study will be to demonstrate that following cessation of vorapaxar in patients with suppressed plasma HIV viremia there will be an increase in the levels of d-dimer over a 6 week period.

Project Members
image - 1338436367 Sean Emery.jpg
Professor Sean Emery
Professor and Program Head
image - 1338437344 Sally Hough Tvrp.jpg
Clinical Project Coordinator
Ph +61 (0)2 9385 0900
image - 1338437138 Anna Donaldson.jpg
Clinical Project Coordinator
Ph +61 (0)2 9385 0900
image - 1338437380 Kymme Courtney Vega.jpg
Data Manager
Ph +61 (0)2 9385 0900
image - Rashelle Raymond Tvrp
Data Manager
Ph +61 (0)2 9385 0915
image - 1338425133 Janaki Amin.jpg
Associate Professor Janaki Amin
Associate Professor and Postgraduate Coordinator
image - 1338437414 Rose Robson.jpg
Administrative Assistant
Ph +61 (0)2 9385 0900
image - 1338430087 David Van Bockel
Research Officer
Ph +61 2 9385 0471
image - Tonykaug 2013
Professor and Program Head
Ph 02 9385 0900
Other Investigators

Doctors at St Vincent’s Hospital, Sydney, Melbourne Sexual Health Centre, Hennepin County Medical Center (USA) including; Prof Anthony Kelleher, Prof David Cooper, Dr Angie Pinto, Dr Kersten Koelsch, Prof Bruce Brew, Prof Stephen Kent, Dr Jason Baker, Dr Robert Finlayson, Dr Marta Catalfamo, Dr Cliff Lane.

Project Collaborators: External

Kent Laboratory – Doherty Institute, Melbourne

St Vincent’s Centre for Applied Medical Research, Sydney

University of Minnesota

National Institute of Health, USA

Project Contacts

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