Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints
| Status: | Completed |
|---|---|
| Conditions: | HIV / AIDS |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 40 - Any |
| Updated: | 3/8/2019 |
| Start Date: | September 2015 |
| End Date: | January 2018 |
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
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.
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.
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.
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.
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.
We found this trial at
3
sites
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