Optimising Metabolic Management for People With Human Immunodeficiency Virus (HIV) on Integrase Based Antiretroviral Therapy (ART)

NCT ID: NCT06317051

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-16
• Study Completion Date: 2026-12-31

Brief Summary

People with HIV are at a higher risk of cardiovascular diseases (CVD) due to the effects of the virus and its treatment. Integrase strand transfer inhibitors (INSTIs), a common HIV treatment, are associated with increased CVD risk and metabolic issues, such as weight gain and high blood pressure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, however, have been working well in reducing CVD events and hospitalizations due to heart failure, irrespective of diabetes presence. They also help in reducing weight and blood pressure. Pitavastatin has shown to work in lowering CVD events in people with HIV, but its availability is limited. This benefit is thought to be common to all statins, but this has not yet been confirmed. This study will examine the impact of dapagliflozin vs. placebo on metabolic parameters in people with HIV with high metabolic risk who are on INSTI-based ART.

Detailed Description

This is a 2x2 factorial, randomised, placebo-controlled, double-blind, phase III/IV trial with two randomisations performed centrally via an on-line system, stratified by site. Participants will be randomised 1:1 to dapagliflozin 10mg vs. Placebo; this randomisation will be blinded. Participants will also be randomised 1:1 within each group to pitavastatin 4mg vs. rosuvastatin 10mg/ezetimibe 10mg; this randomisation will be open label.

Therefore, participants will be randomised to one of 4 groups:

1. Dapagliflozin 10mg + pitavastatin 4mg

2. Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg

3. Placebo + pitavastatin 4mg

4. Placebo + rosuvastatin 10mg/ezetimibe 10mg

With the following 2-arm randomised comparisons:

• Primary analysis hypothesis: a+b vs c+d (dapagliflozin vs placebo)
• Secondary analysis hypothesis: a+c vs b+d (pitavastatin vs rosuvastatin 10mg/ezetimibe 10mg)

The study's primary and secondary endpoints described will assess both efficacy and safety/tolerability across randomisation arms. Follow up will continue to 48 weeks and endpoint measures will be obtained at 4, 12, 24, and 48 weeks. Primary endpoint is at 24 weeks. The total number of participants is 300, with 75 randomised to each of the groups as listed above.

Conditions

HIV Infections; Weight Gain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Dapagliflozin 10mg + pitavastatin 4mg

Dapagliflozin 10mg + pitavastatin 4mg given as daily tablets for 48 weeks

Group Type: ACTIVE_COMPARATOR

Dapagliflozin 10mg Tab

Intervention Type: DRUG

Dapagliflozin will be administered as a comparator to the placebo to assess its effects on weight reduction

Pitavastatin 4 Mg Oral Tablet

Intervention Type: DRUG

Pitavastatin tablets will be administered as a comparator to Rosuvastatin/Ezetimibe 10mg/10mg tablets to assess and compare their effects on LDL concentrations

Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg

Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg given as daily tablets for 48 weeks

Group Type: ACTIVE_COMPARATOR

Dapagliflozin 10mg Tab

Intervention Type: DRUG

Dapagliflozin will be administered as a comparator to the placebo to assess its effects on weight reduction

Rosuvastatin and Ezetimibe

Intervention Type: DRUG

Rosuvastatin/Ezetimibe 10mg/10mg tablets will be administered as a comparator to pitavastatin to assess and compare their effects on LDL concentrations

Placebo + pitavastatin 4mg

Placebo + pitavastatin 4mg given as daily tablets for 48 weeks

Group Type: PLACEBO_COMPARATOR

Pitavastatin 4 Mg Oral Tablet

Intervention Type: DRUG

Pitavastatin tablets will be administered as a comparator to Rosuvastatin/Ezetimibe 10mg/10mg tablets to assess and compare their effects on LDL concentrations

Placebo

Intervention Type: DRUG

The placebo tablets are visually identical to the active drug tablets and will be administered as a comparator to Dapagliflozin.

Placebo + rosuvastatin 10mg/ezetimibe 10mg

Placebo + rosuvastatin 10mg/ezetimibe 10mg given as daily tablets for 48 weeks

Group Type: PLACEBO_COMPARATOR

Rosuvastatin and Ezetimibe

Intervention Type: DRUG

Rosuvastatin/Ezetimibe 10mg/10mg tablets will be administered as a comparator to pitavastatin to assess and compare their effects on LDL concentrations

Placebo

Intervention Type: DRUG

The placebo tablets are visually identical to the active drug tablets and will be administered as a comparator to Dapagliflozin.

Interventions

Dapagliflozin 10mg Tab

Dapagliflozin will be administered as a comparator to the placebo to assess its effects on weight reduction

Intervention Type: DRUG

Pitavastatin 4 Mg Oral Tablet

Pitavastatin tablets will be administered as a comparator to Rosuvastatin/Ezetimibe 10mg/10mg tablets to assess and compare their effects on LDL concentrations

Intervention Type: DRUG

Rosuvastatin and Ezetimibe

Rosuvastatin/Ezetimibe 10mg/10mg tablets will be administered as a comparator to pitavastatin to assess and compare their effects on LDL concentrations

Intervention Type: DRUG

Placebo

The placebo tablets are visually identical to the active drug tablets and will be administered as a comparator to Dapagliflozin.

Intervention Type: DRUG

Other Intervention Names

FORXIGA; Livazo

Eligibility Criteria

Inclusion Criteria

1. Age 40-75 years and at least one of the following risk factors:

1. BMI > 7% increase or > 5kg weight gain since INSTI commencement, or

2. BMI ≥ 30 kg/m2

2. BMI ≥18 kg/m2 prior to INSTI commencement

3. Currently taking INSTI-based ART

4. Sustained virologic response, defined as viral load <200 copies/mL for at least 12 months

5. Current CD4 >250 cells/mm3

6. Informed consent for trial participation

Exclusion Criteria

1. Currently taking a protease inhibitor

2. Indicated to take or already taking high intensity statin

3. estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2

4. Currently taking an SGLT-2 inhibitor or glucagon-like peptide 1 (GLP-1) agonist

5. Absolute contraindication or absolute indication to SGLT2 inhibitor therapy

6. Absolute contraindication to pitavastatin, rosuvastatin, ezetimibe or combination of rosuvastatin/ezetimibe

7. Pregnant or breast feeding

8. Severe hepatic impairment (Child Pugh B or C)

9. Participants receiving any excluded/contraindicated medication

10. Participants who are enrolled into an additional interventional study.

11. Expected inability or unwillingness to participate in study procedures.

12. In the opinion of the investigator, participation in a trial is not in the best interest of the patient.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kirby Institute

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gail Matthews, MD

Role: PRINCIPAL_INVESTIGATOR

Kirby Institute

Locations

Hospital Ramos Mejía

Buenos Aires, , Argentina

St Vincent's Hospital

Sydney, New South Wales, Australia

Austin Health

Melbourne, Victoria, Australia

CART-CRS

Chennai, Tamil Nadu, India

Universiti Malaya Medical Centre

Kuala Lumpur, , Malaysia

Institute of Human Virology, Nigeria

Abuja, , Nigeria

Desmond Tutu Health Foundation

Cape Town, , South Africa

HIV-NAT

Bangkok, , Thailand

Infectious Diseases Institute, Makerere University

Kampala, , Uganda

University of Zimbabwe Clinical Research Centre

Harare, , Zimbabwe

Countries

Argentina; Australia; India; Malaysia; Nigeria; South Africa; Thailand; Uganda; Zimbabwe

Other Identifiers

OPTIMAR

Identifier Type: -

Identifier Source: org_study_id