Clinical Trials

MainTitle

Effects of Biktarvy on CFR in Stable HIV Patients

This study is currently recruiting participants. (see Contacts and Locations)

Verified January 2020 by Marcelo F. Di Carli, MD, FACC, Brigham and Women's Hospital

Sponsor
Brigham and Women's Hospital

Collaborator
Tufts Medical Center
Boston Medical Center

Information provided by (Responsible Party)
Marcelo F. Di Carli, MD, FACC, Brigham and Women's Hospital

ClinicalTrials.gov Identifier
NCT03656783

First received: August 31, 2018
Last updated: January 15, 2020
Last Verified: January 2020
History of Changes
Purpose

Purpose

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a single pill regimen that was approved by the FDA in February 2018 for treatment of HIV. The marketed name of the drug is Biktarvy. In two phase 3 comparative clinical trials, including one with ABC/3TC/DTG, it was found to be non-inferior to dolutegravir-containing regimens in terms of virologic outcomes. B/F/TAF was also well tolerated, with few discontinuations for adverse events. As a result, B/F/TAF is an ideal non-abacavir containing regimen to assess the effect of removing ABC on coronary flow reserve.

Condition Intervention Phase
HIV

Drug : Biktarvy
Phase 3

Study Type: Interventional
Study Design: Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: EFFECTS OF BICTEGRAVIR-EMTRICITABINE-TENOFOVIR ALAFENAMIDE ON CORONARY FLOW RESERVE IN STABLE HIV PATIENTS (B/F/TAF-CFR) - PILOT STUDY

Further study details as provided by Marcelo F. Di Carli, MD, FACC, Brigham and Women's Hospital:

Primary Outcome Measures

  • Change in Global CFR [ Time Frame: 24 weeks ]
    Change (from baseline) in global coronary flow reserve, as measured by PET imaging at 24 weeks after initiation of B/F/TAF therapy.
Secondary Outcome Measures:
  • Change in Peak Stress Global MBF [ Time Frame: 24 weeks ]
    Change (from baseline) in peak-stress global myocardial blood flow (in mL/min/g) at 24 weeks after initiation of B/F/TAF;
  • Change in Peak Stress Global Coronary Vascular Resistance [ Time Frame: 24 weeks ]
    Change (from baseline) in peak-stress global coronary vascular resistance (in mm Hg/mL/min/g) at 24 weeks after initiation of B/F/TAF;
  • Change in Serum Biomarkers of Inflammation [ Time Frame: 24 weeks ]
    Change in serum biomarkers of inflammation (hs-CRP (in mg/L)) at 24 weeks after initiation of B/F/TAF.
  • Change in Serum Biomarkers of Inflammation [ Time Frame: 24 weeks ]
    Change in serum biomarkers of inflammation (IL-6 (in pg/mL)) at 24 weeks after initiation of B/F/TAF.
  • Change in Serum Biomarkers of Inflammation [ Time Frame: 24 weeks ]
    Change in serum biomarkers of inflammation (sCD163 (in mg/L)) at 24 weeks after initiation of B/F/TAF.
  • Change in Serum Biomarkers of Inflammation [ Time Frame: 24 weeks ]
    Change in serum biomarkers of inflammation (sCD14 (in pg/mL)) at 24 weeks after initiation of B/F/TAF.
  • Change in Myocyte Injury and Strain [ Time Frame: 24 weeks ]
    Change in Myocyte Injury and Strain (hs Troponin (in ng/L)) at 24 weeks after initiation of B/F/TAF.
  • Change in Myocyte Injury and Strain [ Time Frame: 24 weeks ]
    Change in Myocyte Injury and Strain (NT-proBNP (in pg/mL)) at 24 weeks after initiation of B/F/TAF.

Estimated Enrollment: 30
Study Start Date: September 14, 2018
Estimated Study Completion Date: November 30, 2020
Estimated Primary Completion Date: November 30, 2020 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Other: HIV patients on stable therapy
Open-label, multicenter, single-arm study
Drug: Biktarvy

Open-label, multicenter, single-arm study to Evaluate the Safety and Efficacy of Switching from Regimens Consisting of Abacavir/Lamivudine/Dolutegravir (ABC/3TC/DTG) to the Bictegravir/ Emtricitabine/Tenofovir Alafenamide (B/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed HIV-Infected Adult Subjects

Other Name: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)

Detailed Description:

Positron emission tomography (PET) imaging allows precise and reproducible quantification of myocardial blood flow, thereby providing a direct assessment of coronary vascular health. Coronary flow reserve (CFR, calculated as the ratio of peak hyperemic myocardial blood flow over that at rest) is emerging as a powerful quantitative prognostic imaging marker of clinical cardiovascular risk. CFR provides a robust and reproducible clinical measure of the integrated hemodynamic effects of epicardial coronary artery disease (CAD), diffuse atherosclerosis, vessel remodeling, and microvascular dysfunction resulting from endothelial cell dysfunction on myocardial tissue perfusion across the entire coronary circulation. These processes have direct relevance to the underlying vascular pathobiology in patients with HIV infection. Consequently, quantitative CFR provides a unique opportunity to examine the potential impact of novel therapies on the biology of the disease and its association with cardiovascular outcomes. By testing the fundamental concept of whether novel ART therapies in HIV can lead to improved coronary blood flow and myocardial tissue perfusion, TAF-CFR would provide important mechanistic insights of the capabilities of TAF therapy to improve key determinants of clinical risk.
This is an open label, multicenter, uncontrolled, single arm pilot study. Patients with stable HIV currently treated with abacavir/lamivudine/dolutegravir STR regimens will be eligible for the B/F/TAF-CFR study. PET scans will be performed after enrollment while on the abacavir/lamivudine/dolutegravir STR regimen and at 24 weeks after the switch to B/F/TAF regimen. Patients will be encouraged to remain on stable medical therapy throughout the enrollment period.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 95 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:
Patients with HIV on abacavir/lamivudine/dolutegravir STR regimens for at least 1 year fulfilling the following inclusion criteria:

    1. age ≥ 45 years for men and ≥ 55 years for women;
    2. at least one coronary risk factor including smoking, dyslipidemia, hypertension, obesity (BMI >30) or diabetes, or a calculated 10-year risk of heart attack of 7.5% or higher;
    3. HIV RNA < 200 copies/mL at last clinical measurement, done within the past 12 months prior to screening, with no intervening HIV RNA > 200;
    4. Screening HIV RNA < 50 copies/mL, CBC, and chemistries that, in the judgment of the investigator, do not preclude the use of Biktarvy.


Exclusion Criteria:
    1. patients not fulfilling inclusion criteria;
    2. unstable HIV disease or other medical condition that, in the opinion of the investigator, would interfere with the conduct of the study;
    3. history of cardiomyopathy (LVEF <40%) or significant valvular heart disease;
    4. cirrhosis;
    5. end stage renal disease on dialysis;
    6. uncontrolled hypertension (defined as SBP >200 or DBP >110);
    7. pregnancy;
    8. Patients requiring medications contraindicated with the components of B/F/TAF;
    9. Patients on active treatment for severe asthma or severe COPD.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03656783

Contacts

Contact:   Marcelo Di Carli, MD 617-732-6290 mdicarli@partners.org
Contact:   Courtney Bibbo, MSc 617-525-8322 cfbibbo@partners.org

Locations

United States, Massachusetts
Tufts Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02111
Contact: Laura Kogelman, MD    lkogelman@tuftsmedicalcenter.org
Contact: Deirdre Burke    DBurke1@tuftsmedicalcenter.org
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Courtney Bibbo, M.Sc.    617-525-8322    cfbibbo@partners.org
Boston Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02118
Contact: Nina Lin, MD    Nina.LIn@bmc.org
Contact: Kristin Brierley    Kristin.Brierley@bmc.org

Sponsors and Collaborators

Brigham and Women's Hospital
Tufts Medical Center
Boston Medical Center

Investigators

Principal Investigator: Marcelo Di Carli, MD Brigham and Women's Hospital
More Information

More Information


Responsible Party: Marcelo F. Di Carli, MD, FACC, Chief of Nuclear Medicine, Brigham and Women's Hospital  
ClinicalTrials.gov Identifier: NCT03656783   History of Changes  
Other Study ID Numbers: 2018P001579  
Study First Received: August 31, 2018  
Last Updated: January 15, 2020  
Individual Participant Data    
Plan to Share IPD: No  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  
Product Manufactured in and Exported from the U.S.: Yes  

Additional relevant MeSH terms:
Tenofovir
Emtricitabine

ClinicalTrials.gov processed this data on June 02, 2020
This information is provided by ClinicalTrials.gov.