HIV Clinical Trial
— ADVICEOfficial title:
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
Verified date | March 2019 |
Source | Kirby Institute |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 65 |
Est. completion date | January 2018 |
Est. primary completion date | November 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 40 Years and older |
Eligibility |
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. |
Country | Name | City | State |
---|---|---|---|
Australia | Melbourne Sexual Health Centre | Carlton | Victoria |
Australia | St Vincent's Hospital | Darlinghurst | New South Wales |
Australia | Taylor Square Private Clinic | Darlinghurst | New South Wales |
Australia | Monash Medical Centre | Melbourne | Victoria |
Australia | Northside Clinic | North Fitzroy | Victoria |
United States | Georgetown University Hospital | Georgetown | Maryland |
United States | Hennepin County Medical Centre | Minneapolis | Minnesota |
Lead Sponsor | Collaborator |
---|---|
Kirby Institute | Merck Sharp & Dohme Corp., National Institute of Allergy and Infectious Diseases (NIAID), University of Melbourne, University of Minnesota - Clinical and Translational Science Institute |
United States, Australia,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Number of Participants in Each Treatment Group With Plasma HIV-1 RNA <50 Copies/mL | Number of participants in each treatment group with plasma HIV-1 RNA <50 copies/mL at week 18 | at week 18 | |
Secondary | Mean Change From Baseline to Week 12 in CD4+ Cell Counts | Mean of week 12 CD4+ cell count minus mean of week 0 CD4+ cell count | at week 12 | |
Secondary | Mean Change From Baseline to Week 12 in CD8+ Cell Counts | Mean of week 12 CD8+ cell count minus mean of week 0 CD4+ cell count | at week 12 | |
Secondary | Number of Patients in Each Treatment Group With D-dimer <165ng/mL at Week 12 | Number of patients in each treatment group with d-dimer <165ng/mL at week 12 | week 12 | |
Secondary | Number of Patients in Each Treatment Group With D-dimer > or Equal to 165ng/mL at Week 18 | Number of patients in each treatment group with d-dimer > or equal to 165ng/mL at week 18 | week 18 | |
Secondary | Mean Change From Baseline in log10 D-Dimer | Differences between treatment groups in mean change from week 0 log10 d-dimer to week 18 | at week 18 | |
Secondary | Mean Change From Baseline in log10 Hs-CRP at Week 18 | Differences between treatment groups in mean change from baseline log10 hs-CRP to week 18. ie Week 18 log10 hs-CRP minus week 0 log10 hs-CRP | at week 18 | |
Secondary | Percent Change From Baseline Hs-CRP (ug/mL) to the Average of Week 8 and Week 12 | Mean of week 8 and week 12 minus week 0 (on log10 scale) then back transformed the log10 difference to obtain percentage change from baseline. | week 8 and 12 | |
Secondary | Mean Percent Change From Baseline IL-6 (pg/mL) to the Average of Week 8 and Week 12 | Mean of week 8 and week 12 minus week 0 (on log10 scale) then back transformed the log10 difference to obtain percentage change from baseline. | at week 8 and week 12 | |
Secondary | Differences Between Treatment Groups in Mean Change From Baseline log10 IL-6 | Differences between treatment groups in mean change from baseline log10 IL-6 at week 18 | at week 18 | |
Secondary | Total Number of Participants With BARC Type 1, 2, 3, 4, or 5 Bleeding Episodes | Bleeding Academic Research Consortium (BARC) Definitions for Bleeding Events Type 1 -bleeding that is not actionable and does not cause the patient to seek unscheduled performance of studies, hospitalization, or treatment by a healthcare professional; may include episodes leading to self-discontinuation of medical therapy by the patient without consulting a healthcare professional Type 2 - overt, actionable sign of haemorrhage (eg, more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for type 3, 4, or 5 but does meet at least one of the following criteria: (1) requiring nonsurgical, medical intervention by a healthcare professional, (2) leading to hospitalization or increased level of care, or (3) prompting evaluation Type 3- Bleeding requiring surgical intervention for control (excluding dental/nasal/skin/hemorrhoid) Type 4 - Coronary Artery Bypass Graft procedure-related bleeding Type 5 - | at week 18 | |
Secondary | Total Number of Participants With Any SAE Between Baseline and Week 18 | Total number of participants with any SAE between baseline and week 18 | week 18 | |
Secondary | Total Number of Participants With Any AE Between Baseline to Week 18 | Total number of participants with any AE between week 0 to week 18 | week 18 | |
Secondary | Changes From Baseline in Renal Function Measured by the CKD-EPI Estimate of Creatinine Clearance at Week 12 | Changes from baseline in renal function measured by the CKD-EPI estimate of creatinine clearance at week 12 | at week 12 |
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