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HIVPhase 1/2ADVICENCT02394730

Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints

A Phase 1/2 study testing vorapaxar in people with HIV, run by Kirby Institute at 7 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
HIV
What is being tested?
vorapaxar
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
65 participants
Where
7 sitesin 2 countries
Study dates
Sep 2015to Jan 2018
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • HIV-1 positive by licensed diagnostic test
  • aged ≥40 years
  • plasma HIV RNA <50 copies/mL for at least 24 weeks
  • screening CD4+ cell count > 50 cells/mm3
  • 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)
  • 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)
  • provision of written informed consent

Who cannot join

  • Absolute neutrophil count (ANC) <1000 cells/μL
  • hemoglobin <10.0 g/dL
  • platelet count <75,000 cells/μL
  • AST and/or ALT >2.5 x ULN
  • estimated glomerular filtration rate <30mL/min/1.73m2 ) using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation
  • history of myocardial infarction or unstable atherosclerotic disease
Show all 14Show fewer
  • history of ischemic stroke or transient ischaemic attack (TIA)
  • active peptic/duodenal ulcer or other bleeding disorder within the previous 12 months
  • intent to have surgery within the 6 month period after randomisation
  • current use of aspirin or P2Y12 antiplatelet therapy
  • 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.
  • participants unlikely to be able to remain in follow-up
  • pregnant or nursing mothers
  • 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.

Trial locations and contacts

7 sites in 2 countries.

7 sites in 2 countries

Australia5 sites

  • Melbourne Sexual Health Centre

    Carlton, Victoria, 3053

  • St Vincent's Hospital

    Darlinghurst, New South Wales, 2010

  • Taylor Square Private Clinic

    Darlinghurst, New South Wales, 2010

  • Northside Clinic

    Fitzroy North, Victoria, 3068

  • Monash Medical Centre

    Melbourne, Victoria, 3168

Other trials in Australia

United States2 sites

  • Georgetown University Hospital

    Georgetown, Maryland, 20007

  • Hennepin County Medical Centre

    Minneapolis, Minnesota, 55415

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
HIV
Being tested
vorapaxar, Placebo
Keywords
HIV, d-dimer, hs-CRP, activated T-lymphocytes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • vorapaxarDrug

    Also called Zontivity

    2.5mg of vorapaxar taken orally once daily for 12 weeks

  • PlaceboDrug

    Also called sugar pill

    Sugar pill taken orally once daily for 12 weeks

Study groups in NCT02394730
Study groupRoleWhat they receive
vorapaxarExperimental2.5mg of vorapaxar po qd
Receives: Drug: vorapaxar
PlaceboPlacebo comparatorsugar pill po qd
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: at week 8 and week 12

Secondary outcomes (14)

  1. 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

    Measured: at week 18

  2. 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

    Measured: at week 12

  3. 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

    Measured: at week 12

  4. 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

    Measured: week 12

  5. 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

    Measured: week 18

  6. Mean Change From Baseline in log10 D-Dimer

    Differences between treatment groups in mean change from week 0 log10 d-dimer to week 18

    Measured: at week 18

  7. 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

    Measured: at week 18

  8. 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.

    Measured: week 8 and 12

  9. 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.

    Measured: at week 8 and week 12

  10. 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

    Measured: at week 18

  11. 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 -

    Measured: at week 18

  12. Total Number of Participants With Any SAE Between Baseline and Week 18

    Total number of participants with any SAE between baseline and week 18

    Measured: week 18

  13. 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

    Measured: week 18

  14. 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

    Measured: at week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2015 (estimated)
  2. Study startSep 2015
  3. Primary completionNov 2017
  4. Study completionJan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02394730
Sponsor's protocol ID
2014-01-ADV
Other IDs
AI000585-26-288416
Acronym
ADVICE
Status last verified
Mar 2019
First submitted
16 Mar 2015
Last updated
6 Mar 2019
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • ADVICE study group. Vorapaxar for HIV-associated inflammation and coagulopathy (ADVICE): a randomised, double-blind, placebo-controlled trial. Lancet HIV. 2018 Oct;5(10):e553-e559. doi: 10.1016/S2352-3018(18)30214-5. Epub 2018 Sep 23.

    PubMed 30257802

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing vorapaxar in people with HIV, run by Kirby Institute at 7 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Australia, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Percent Change From Baseline for D-dimer (ng/mL) to the Average of Weeks 8 and 12 (time frame: at week 8 and week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02394730, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2019.

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