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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02394730




Registration number
NCT02394730
Ethics application status
Date submitted
16/03/2015
Date registered
20/03/2015
Date last updated
6/03/2019

Titles & IDs
Public title
Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints
Scientific 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
Secondary ID [1] 0 0
AI000585-26-288416
Secondary ID [2] 0 0
2014-01-ADV
Universal Trial Number (UTN)
Trial acronym
ADVICE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - vorapaxar
Treatment: Drugs - Placebo

Experimental: vorapaxar - 2.5mg of vorapaxar po qd

Placebo Comparator: Placebo - sugar pill po qd


Treatment: Drugs: vorapaxar
2.5mg of vorapaxar taken orally once daily for 12 weeks

Treatment: Drugs: Placebo
Sugar pill taken orally once daily for 12 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
at week 8 and week 12
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
at week 18
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
at week 12
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
at week 12
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
week 12
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
week 18
Secondary outcome [6] 0 0
Mean Change From Baseline in log10 D-Dimer - Differences between treatment groups in mean change from week 0 log10 d-dimer to week 18
Timepoint [6] 0 0
at week 18
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
at week 18
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
week 8 and 12
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
at week 8 and week 12
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
at week 18
Secondary outcome [11] 0 0
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 -
Timepoint [11] 0 0
at week 18
Secondary outcome [12] 0 0
Total Number of Participants With Any SAE Between Baseline and Week 18 - Total number of participants with any SAE between baseline and week 18
Timepoint [12] 0 0
week 18
Secondary outcome [13] 0 0
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
Timepoint [13] 0 0
week 18
Secondary outcome [14] 0 0
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
Timepoint [14] 0 0
at week 12

Eligibility
Key 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
Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Taylor Square Private Clinic - Darlinghurst
Recruitment hospital [3] 0 0
Melbourne Sexual Health Centre - Carlton
Recruitment hospital [4] 0 0
Monash Medical Centre - Melbourne
Recruitment hospital [5] 0 0
Northside Clinic - North Fitzroy
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3053 - Carlton
Recruitment postcode(s) [3] 0 0
3168 - Melbourne
Recruitment postcode(s) [4] 0 0
3068 - North Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Maryland
Country [2] 0 0
United States of America
State/province [2] 0 0
Minnesota

Funding & Sponsors
Primary sponsor type
Other
Name
Kirby Institute
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Institute of Allergy and Infectious Diseases (NIAID)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
University of Minnesota
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
University of Melbourne
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Commercial sector/Industry
Name [4] 0 0
Merck Sharp & Dohme Corp.
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT02394730
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sean Emery
Address 0 0
University of NSW, Kirby Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications