Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints
Information source: Kirby Institute
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV
Intervention: vorapaxar (Drug); Placebo (Drug)
Phase: Phase 1/Phase 2
Status: Not yet recruiting
Sponsored by: Kirby Institute Official(s) and/or principal investigator(s): Sean Emery, Study Director, Affiliation: University of NSW, Kirby Institute
Overall contact: Sally Hough, BAppSc, Phone: +61 2 93850900, Ext: 0897, Email: shough@kirby.unsw.edu.au
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.
Clinical Details
Official 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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Differences between treatment groups in mean change from baseline log10- d-dimer
Secondary outcome: Proportion of participants in each treatment group with plasma HIV-1 RNA <50 copies/mLDifferences between treatment groups in mean change from baseline in CD4+ cell counts Differences between treatment groups in mean change from baseline in CD8+ cell counts Percentage of patients in each treatment group with d-dimer <165ng/mL Percentage of patients in each treatment group with d-dimer >165ng/mL Differences between treatment groups in mean change from baseline log10 d-dimer Differences between treatment groups in mean change from baseline log10 hs-CRP Differences between treatment groups in mean change from baseline log10 hs-CRP Differences between treatment groups in mean change from baseline log10 IL-6 Differences between treatment groups in mean change from baseline log10 IL-6 Total number of participants with BARC Type 1, 2, 3, 4, or 5 bleeding episodes Total number of participants with any SAE and the cumulative incidence of SAEs Total number of participants with any AE and the cumulative incidence of AEs Changes from baseline in selected serum biochemical parameters including changes in renal function measured by the CKD-EPI estimate of creatinine clearance
Detailed description:
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.
Eligibility
Minimum age: 40 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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 with cART regimen that contains NRTIs in combination with either raltegravir
or dolutegravir for at least 24 weeks
6. plasma d-dimer >200ng/mL (>0. 2μg/mL or >0. 2mg/L) 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≤60mL/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 other contraindicated medications, including anticoagulants, (eg. heparin or
warfarin), fibrinolytic therapy, chronic use (more than 5 consecutive days) of
nonsteroidal anti-inflammatory drugs (NSAIDS), selective serotonin reuptake
inhibitors, serotonin norepinephrine reuptake inhibitors, strong CYP3A4 inhibitors or
inducers. See Manual of Operations for full list of contraindicated medications.
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.
Locations and Contacts
Sally Hough, BAppSc, Phone: +61 2 93850900, Ext: 0897, Email: shough@kirby.unsw.edu.au
National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, United States; Not yet recruiting Alexander Ober, Phone: 301-435-7912, Email: Alexander.Ober@nih.gov
Hennepin County Medical Centre, Minneapolis, Minnesota 55415, United States; Not yet recruiting Jason Baker, Phone: 612-873-6876, Email: baker@umn.edu
St Vincent's Hospital, Darlinghurst, New South Wales 2010, Australia; Not yet recruiting Karen MacRae, Phone: +61283822670, Email: Karen.MacRae@svha.org.au
Melbourne Sexual Health Centre, Carlton, Victoria 3053, Australia; Not yet recruiting Julie Silvers, Phone: +61393416262, Email: ResearchUnit@mshc.org.au
Additional Information
Starting date: June 2015
Last updated: March 16, 2015
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