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

NCT06317051 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: OPTIMAR
• Study Type: interventional
• Target: 300
• Locations: 9 countries
• Sites: 10

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.

Conditions

HIV Infections; Weight Gain

Keywords

HIV

Outcome Measures

Primary Outcomes (2)

• To assess the impact of dapagliflozin vs. placebo on weight reduction

  Mean reduction change in body weight across treatment arms at 24 weeks, defined as absolute body weight change.

  24 weeks

• To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe on low-density lipoproteins (LDL) concentration

  Mean change in LDL as absolute change from baseline to 24 weeks across treatment arms

  24 weeks

Secondary Outcomes (15)

• To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on body mass index (BMI )- weight and height will be combined to report BMI in kg/m^2

  48 weeks

• To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on waist (cm) to hip (cm) ratio

  48 weeks

• To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on waist (cm) to height (cm) ratio

  48 weeks

• To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on systolic and diastolic blood pressure (mm Hg)

  48 weeks

• To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on Atherosclerotic cardiovascular disease risk score (ASCVD) - calculation of a person's10-year risk (%) of having a cardiovascular problem.

  48 weeks

Study Arms (4)

Dapagliflozin 10mg + pitavastatin 4mg

ACTIVE COMPARATOR

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

Drug: Dapagliflozin 10mg Tab; Drug: Pitavastatin 4 Mg Oral Tablet

Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg

ACTIVE COMPARATOR

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

Drug: Dapagliflozin 10mg Tab; Drug: Rosuvastatin and Ezetimibe

Placebo + pitavastatin 4mg

PLACEBO COMPARATOR

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

Drug: Pitavastatin 4 Mg Oral Tablet; Drug: Placebo

Placebo + rosuvastatin 10mg/ezetimibe 10mg

PLACEBO COMPARATOR

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

Drug: Rosuvastatin and Ezetimibe; Drug: Placebo

Interventions

Dapagliflozin 10mg Tab DRUG

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

Also known as: FORXIGA

Dapagliflozin 10mg + pitavastatin 4mg; Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg

Rosuvastatin and Ezetimibe DRUG

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

Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg; Placebo + rosuvastatin 10mg/ezetimibe 10mg

Placebo DRUG

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

Placebo + pitavastatin 4mg; Placebo + rosuvastatin 10mg/ezetimibe 10mg

Pitavastatin 4 Mg Oral Tablet DRUG

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

Also known as: Livazo

Dapagliflozin 10mg + pitavastatin 4mg; Placebo + pitavastatin 4mg

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 40-75 years and at least one of the following risk factors:
• BMI \> 7% increase or \> 5kg weight gain since INSTI commencement, or
• BMI ≥ 30 kg/m2
• BMI ≥18 kg/m2 prior to INSTI commencement
• Currently taking INSTI-based ART
• Sustained virologic response, defined as viral load \<200 copies/mL for at least 12 months
• Current CD4 \>250 cells/mm3
• Informed consent for trial participation

You may not qualify if:

• Currently taking a protease inhibitor
• Indicated to take or already taking high intensity statin
• estimated glomerular filtration rate (eGFR) \< 30 ml/min/1.73m2
• Currently taking an SGLT-2 inhibitor or glucagon-like peptide 1 (GLP-1) agonist
• Absolute contraindication or absolute indication to SGLT2 inhibitor therapy
• Absolute contraindication to pitavastatin, rosuvastatin, ezetimibe or combination of rosuvastatin/ezetimibe
• Pregnant or breast feeding
• Severe hepatic impairment (Child Pugh B or C)
• Participants receiving any excluded/contraindicated medication
• Participants who are enrolled into an additional interventional study.
• Expected inability or unwillingness to participate in study procedures.
• In the opinion of the investigator, participation in a trial is not in the best interest of the patient.

Sponsors & Collaborators

• Kirby Institute: lead

Study Sites (10)

Hospital Ramos Mejía

Buenos Aires, Argentina

Location

St Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

Austin Health

Melbourne, Victoria, 3084, Australia

Location

CART-CRS

Chennai, Tamil Nadu, 600113, India

Location

Universiti Malaya Medical Centre

Kuala Lumpur, Malaysia

Location

Institute of Human Virology, Nigeria

Abuja, Nigeria

Location

Desmond Tutu Health Foundation

Cape Town, 7925, South Africa

Location

HIV-NAT

Bangkok, Thailand

Location

Infectious Diseases Institute, Makerere University

Kampala, Uganda

Location

University of Zimbabwe Clinical Research Centre

Harare, Zimbabwe

Location

MeSH Terms

Conditions

HIV Infections; Weight Gain

Interventions

dapagliflozin; pitavastatin; Tablets; Rosuvastatin Calcium; Ezetimibe

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azetidines; Azetines

Study Officials

• Gail Matthews, MD

  Kirby Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2024
• First Posted: March 19, 2024
• Study Start: December 16, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 10, 2025

Record last verified: 2025-12

Locations

ZI (1); AR (1); AU (2); MY (1); UG (1); IN (1); NG (1); ZA (1); TH (1)