HIVPhase 3BETTERNCT03656783

Effects of Biktarvy on CFR in Stable HIV Patients

A Phase 3 study testing Biktarvy in people with HIV, run by Brigham and Women's Hospital at 3 sites in United States.

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

Who is it for?: Ages 18 to 95 years
Conditions the study is for: HIV
What is being tested?: Biktarvy
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 25 participants
Where: 3 sitesUnited States
Study dates: 14 Sep 2018to 15 Sep 2021
Phase: Phase 3
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 18 to 95 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients with HIV on abacavir/lamivudine/dolutegravir STR regimens for at least 1 year fulfilling the following inclusion criteria:
age ≥ 45 years for men and ≥ 55 years for women;
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;
HIV RNA < 200 copies/mL at last clinical measurement, done within the past 12 months prior to screening, with no intervening HIV RNA > 200;
Screening HIV RNA < 50 copies/mL, CBC, and chemistries that, in the judgment of the investigator, do not preclude the use of Biktarvy.

Who cannot join

patients not fulfilling inclusion criteria;
unstable HIV disease or other medical condition that, in the opinion of the investigator, would interfere with the conduct of the study;
history of cardiomyopathy (LVEF <40%) or significant valvular heart disease;
cirrhosis;
end stage renal disease on dialysis;
uncontrolled hypertension (defined as SBP >200 or DBP >110);

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pregnancy;
Patients requiring medications contraindicated with the components of B/F/TAF;
Patients on active treatment for severe asthma or severe COPD.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Tufts Medical Center
Boston, Massachusetts, 02111
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Boston Medical Center
Boston, Massachusetts, 02118

Other trials in United States

About this study

Official title: Effects of Biectegravir-Emtricitabine-Tenofovir Alafenamide on Coronary Flow Reserve in Stable HIV Patients (B/F/TAF-CFR) - Pilot Study

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.

Read the 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.

Conditions: HIV
Being tested: Biktarvy

What participants receive

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

BiktarvyDrug
Also called Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)
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

Study groups in NCT03656783
Study group	Role	What they receive
HIV patients on stable therapy	Other	HIV patients on stable therapy switching from Abacavir/Lamivudine/Dolutegravir (ABC/3TC/DTG) to the Bictegravir/ Emtricitabine/Tenofovir Alafenamide (B/F/TAF) Receives: Drug: Biktarvy

What is being measured

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

Change in Global CFR
Change in global coronary flow reserve, as measured by PET imaging at baseline and 24 weeks after initiation of B/F/TAF therapy.
Coronary flow reserve (CFR), the ratio of peak vasodilator stress to rest myocardial blood flow (MBF), represents the maximal ability to augment coronary flow and myocardial perfusion. Absolute MBF was computed from the rest and stress myocardial perfusion PET images using commercially available software (Corridor4DM; Ann Arbor, Michigan) and a two-compartment tracer kinetic model. Impaired MBFR is defined as a ratio of <2.0, which is associated with increased cardiovascular risk.
Measured: baseline and week 24

Secondary outcomes (4)

Change in Peak Stress Global MBF
Change (from baseline) in peak-stress global myocardial blood flow (in mL/min/g) at 24 weeks after initiation of B/F/TAF.
Absolute MBF was computed from the rest and stress myocardial perfusion PET images using commercially available software (Corridor4DM; Ann Arbor, Michigan) and a two-compartment tracer kinetic model. Impaired stress MBF is defined as <1.8 mL/min/g and is associated with increased cardiovascular risk.
Measured: baseline and 24 weeks
Change in Serum Biomarkers of Inflammation (Hs-CRP (in mg/L))
Change in serum biomarkers of inflammation (hs-CRP (in mg/L)) at 24 weeks after initiation of B/F/TAF.
Serum biomarkers of inflammation (high sensitivity C-reactive protein) were measured. hs-CRP > 1 mg/L are considered abnormal and associated with increased cardiovascular risk.
Measured: Baseline and 24 weeks
Change in Myocyte Injury and Strain (hs Troponin (in ng/L))
Change in Myocyte Injury and Strain (hs Troponin (in ng/L)) at 24 weeks after initiation of B/F/TAF.
Serum biomarkers of myocardial injury/strain (high sensitivity troponin) were measured. hs-troponin >14 ng/L are considered abnormal and associated with increased cardiovascular risk.
Measured: Baseline and 24 weeks
Change in Myocyte Injury and Strain (NT-proBNP (in pg/mL))
Change in Myocyte Injury and Strain (NT-proBNP (in pg/mL)) at 24 weeks after initiation of B/F/TAF.
Serum biomarkers of myocardial injury/strain (NT-pro-BNP) were measured. NT-proBNP > 100 pg/mL are considered abnormal and associated with increased cardiovascular risk.
Measured: Baseline and 24 weeks

Timeline

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

14 Sep 201815 Sep 2021

First posted4 Sep 2018
Study start14 Sep 2018
Primary completion15 Sep 2021
Study completion15 Sep 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIVStudies of the same condition, open and under way.
More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03656783
Sponsor's protocol ID: 2018P001579
Acronym: BETTER
Status last verified: Jan 2023
First submitted: 31 Aug 2018
Last updated: 8 Feb 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Huck DM, Weber B, Parks S, Divakaran S, Brown JM, Bibbo CF, Barrett L, Hainer J, Bay C, Martell L, Kogelman L, Triant VA, Chu J, Lin NH, Melbourne K, Sax PE, Di Carli MF. Coronary Microcirculatory Dysfunction in People With HIV and Its Association With Antiretroviral Therapy. J Am Heart Assoc. 2023 Nov 21;12(22):e029541. doi: 10.1161/JAHA.123.029541. Epub 2023 Nov 10.
PubMed 37947105

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Biectegravir-Emtricitabine-Tenofovir Alafenamide on Coronary Flow Reserve in Stable HIV Patients (B/F/TAF-CFR) - Pilot Study
ClinicalTrials.gov ID: NCT03656783
Acronym / sponsor ID: BETTER / 2018P001579
Conditions: HIV
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: Brigham and Women's HospitalUniversity, hospital or other
Collaborators: Tufts Medical Center, Boston Medical Center
Study start: 14 Sep 2018 (actual)
Primary completion: 15 Sep 2021 (actual)
Study completion: 15 Sep 2021 (actual)
First posted: 4 Sep 2018 (actual)
Results: Posted 8 Feb 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
HIV patients on stable therapy	Other	Drug: BiktarvyHIV patients on stable therapy switching from Abacavir/Lamivudine/Dolutegravir (ABC/3TC/DTG) to the Bictegravir/ Emtricitabine/Tenofovir Alafenamide (B/F/TAF)

Who may qualify

Ages: 18 to 95 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Patients with HIV on abacavir/lamivudine/dolutegravir STR regimens for at least 1 year fulfilling the following inclusion criteria:
age ≥ 45 years for men and ≥ 55 years for women;
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;
HIV RNA < 200 copies/mL at last clinical measurement, done within the past 12 months prior to screening, with no intervening HIV RNA > 200;
Screening HIV RNA < 50 copies/mL, CBC, and chemistries that, in the judgment of the investigator, do not preclude the use of Biktarvy.

Key exclusion criteria (9 listed)

patients not fulfilling inclusion criteria;
unstable HIV disease or other medical condition that, in the opinion of the investigator, would interfere with the conduct of the study;
history of cardiomyopathy (LVEF <40%) or significant valvular heart disease;
cirrhosis;
end stage renal disease on dialysis;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BiktarvyAlso: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)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	Drug	HIV patients on stable therapy

Primary outcome

Change in Global CFR
Time frame: baseline and week 24
Change in global coronary flow reserve, as measured by PET imaging at baseline and 24 weeks after initiation of B/F/TAF therapy. Coronary flow reserve (CFR), the ratio of peak vasodilator stress to rest myocardial blood flow (MBF), represents the maximal ability to augment coronary flow and myocardial perfusion. Absolute MBF was computed from the rest and stress myocardial perfusion PET images using commercially available software (Corridor4DM; Ann Arbor, Michigan) and a two-compartment tracer kinetic model. Impaired MBFR is defined as a ratio of <2.0, which is associated with increased cardiovascular risk.

4 secondary outcomes

Change in Peak Stress Global MBF
Time frame: baseline and 24 weeks
Change in Serum Biomarkers of Inflammation (Hs-CRP (in mg/L))
Time frame: Baseline and 24 weeks
Change in Myocyte Injury and Strain (hs Troponin (in ng/L))
Time frame: Baseline and 24 weeks
Change in Myocyte Injury and Strain (NT-proBNP (in pg/mL))
Time frame: Baseline and 24 weeks

Results and safety

Results posted to the registry on 8 Feb 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
HIV Patients on Stable Therapy	25	25

Primary outcome: Change in Global CFR

Time frame: baseline and week 24. Mean (95% Confidence Interval). Unit: ratio

Measure	HIV Patients on Stable Therapy n = 25
Value	-.05 (-.25 to 0.15)

Population analysed: We enrolled men 45 years and over and women 55 years and over with HIV who were stable on a DTG/3TC/ABC regimen with virologic suppression for at least one year, and with at least one coronary risk factor (current smoking, dyslipidemia, hypertension, diabetes, obesity, or a calculated 10-year predicted risk of cardiovascular events of 7.5 percent or over) but without overt cardiovascular disease.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Event data was collected from consent through 24-week End of Treatment visit.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
HIV Patients on Stable	0 of 25 (0%)	2 of 25 (8%)	0 of 25

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37947105Huck DM, Weber B, Parks S, Divakaran S, Brown JM, Bibbo CF, Barrett L, Hainer J, Bay C, Martell L, Kogelman L, Triant VA, Chu J, Lin NH, Melbourne K, Sax PE, Di Carli MF. Coronary Microcirculatory Dysfunction in People With HIV and Its Association With Antiretroviral Therapy. J Am Heart Assoc. 2023 Nov 21;12(22):e029541. doi: 10.1161/JAHA.123.029541. Epub 2023 Nov 10.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Marcelo Di Carli, MD principal investigator

Brigham and Women's Hospital

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Biktarvy in people with HIV, run by Brigham and Women's Hospital at 3 sites in United States.

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 5 inclusion and 9 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 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 8 Feb 2023). 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?

Change in Global CFR (time frame: baseline and week 24). 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 NCT03656783, 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 8 Feb 2023.