Attenuation of D-dimer using Vorapaxar to target Inflammatory and Coagulation Endpoints (ADVICE)
Some people with HIV infection (even very well controlled HIV infection) are at increased risk of death and both fatal and non-fatal episodes of cardiovascular, renal and hepatic disease and cancer. Higher than normal levels of chemicals in the body associated with blood clotting, immune activation and inflammation appear to be closely associated with these unwelcome outcomes. While combination antiretroviral therapy (cART) helps to reduce the level of these chemicals, people with HIV infection still have higher levels of these chemicals than people without HIV infection. Interventions to target a reduction in these biomarkers of coagulation and inflammation may lead to improved prognosis for people living with HIV.
The main purpose of the ADVICE study is to compare the safety and efficacy of vorapaxar (anti-clotting medication) versus a placebo sugar pill in reducing levels of chemical markers of clotting (d-dimer), immune activation and immune inflammation in people with well controlled HIV infection. Vorapaxar may help to lower the level of these chemicals in the body.
This is an international study where 60 participants from the USA and Australia will be randomly assigned to receive either vorapaxar or placebo for 12 weeks. Participants will then have a 6 week ‘washout period’ with no study drug and a final visit at week 18. Participants are closely monitored for any possible side effects and various blood samples will be taken to measure the impact of vorapaxar on biomarkers of clotting, inflammation and the immune system.
We expect to have the final results in 2017. We hypothesise that the participants who receive vorapaxar will have lower levels of clotting chemicals and possibly biomarkers of inflammation and immune activation than those who receive placebo, whilst still having well controlled HIV. If this result is achieved, then we hope to conduct a much larger study to see if vorapaxar may actually reduce the occurrence of death and serious illnesses in people with well controlled HIV.
The findings of this study could potentially improve the long term prognosis for the many people living with HIV across the world.
- Georgetown University Medical Centre – Washington, USA
- Hennepin County Medical Center – Minnesota, USA
- Melbourne Sexual Health Centre – Victoria
- Monash Medical Centre – Victoria
- National Institute of Allergy and Infectious Diseases (NIAID) – Maryland, USA
- Northside Clinic – Victoria
- St Vincent's Hospital – New South Wales
- Taylor Square Private Clinic – New South Wales
- National Health and Medical Research Council (NHMRC) with study drug donated by Merck Sharp & Dohme