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NCT Number: NCT06317051

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

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

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

Age range

40 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Ramos Mejía, Buenos Aires, Argentina

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About this study

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:

  • Dapagliflozin 10mg + pitavastatin 4mg
  • Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg
  • Placebo + pitavastatin 4mg
  • 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.

All randomised participants who have not withdrawn from the study will be invited to attend an optional observational follow-up visit at Week 96 (±6 weeks). The visit will collect longer-term post-treatment clinical, metabolic, cardiovascular risk, liver-related, medication use and safety data. No study drug will be supplied beyond Week 48, and no Week 96 CT coronary angiogram is planned. Week 96 data will be analysed separately as exploratory observational post-treatment follow-up data and will not alter the primary Week 24 or Week 48 analyses.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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.

Treatment and study plan

Dapagliflozin 10mg Tab

Drug

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

Other names: FORXIGA

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

Other names: Livazo

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

Placebo

Drug

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

Primary outcomes

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

    Time frame: 24 weeks

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

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

    Time frame: 24 weeks

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

Secondary outcomes

  1. 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

    Time frame: 48 weeks

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

    Time frame: 48 weeks

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

    Time frame: 48 weeks

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

    Time frame: 48 weeks

  5. 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.

    Time frame: 48 weeks

  6. To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on fasting lipids including: Total Cholesterol (mmol/L), LDL (mmol/L), High-Density Lipoproteins (HDL) (mmol/L), Triglycerides (mmol/L)

    Time frame: 48 weeks

  7. To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on fasting glucose (mmol/L)

    Time frame: 48 weeks

  8. To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on haemoglobin A1C (%)

    Time frame: 48 weeks

  9. To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on measures of fatty liver disease: Liver Function Tests - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (U/L), FibroScan (kPa)

    Time frame: 48 weeks

  10. To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on inflammatory biomarkers (tested centrally on stored research samples)

    Time frame: 48 weeks

  11. To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on Serious adverse events.

    Time frame: 48 weeks

  12. To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe from baseline to 48 weeks on fasting lipids including: Total Cholesterol (mmol/L), LDL (mmol/L), High-Density Lipoproteins (HDL) (mmol/L), Triglycerides (mmol/L)

    Time frame: 48 weeks

  13. To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe from baseline to 48 weeks on Atherosclerotic cardiovascular disease risk score (ASCVD) - calculation of a person's10-year risk (%) of having a cardiovascular problem.

    Time frame: 48 weeks

  14. To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe from baseline to 48 weeks on inflammatory biomarkers (tested centrally on stored research samples)

    Time frame: 48 weeks

  15. To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe from baseline to 48 weeks on serious adverse events

    Time frame: 48 weeks

Other outcomes

  1. Change in body weight from baseline to Week 96

    Time frame: Baseline to Week 96

    Absolute change in body weight, measured in kilograms, from baseline to Week 96.

  2. Change in waist-to-hip and waist-to-height ratios from baseline to Week 96

    Time frame: Baseline to Week 96

    Change in waist-to-hip ratio and waist-to-height ratio from baseline to Week 96.

  3. Change in systolic and diastolic blood pressure from baseline to Week 96

    Time frame: Baseline to Week 96

    Change in resting systolic and diastolic blood pressure, measured in mmHg, from baseline to Week 96.

  4. Change in atherosclerotic cardiovascular disease risk score from baseline to Week 96

    Time frame: Baseline to Week 96

    Change in calculated 10-year atherosclerotic cardiovascular disease risk, expressed as a percentage, from baseline to Week 96.

  5. Change in fasting lipids from baseline to Week 96

    Time frame: Baseline to Week 96

    Change in total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides, measured in mmol/L, from baseline to Week 96.

  6. Clinical events of interest after completion of study treatment

    Time frame: Week 48 to Week 96

    Number and type of protocol-specified clinical events of interest reported after the Week 48 visit.

  7. Medication use after completion of study treatment

    Time frame: At Week 96

    Current antiretroviral therapy and use of relevant concomitant medications, including lipid-lowering therapy, SGLT2 inhibitors, GLP-1 receptor agonists, diabetes medications, antihypertensives and cardiovascular medications.

  8. Change in liver fibrosis measures from baseline to Week 96

    Time frame: Baseline to Week 96

    Change in FibroScan liver stiffness, measured in kPa where available, or AST-to-Platelet Ratio Index where FibroScan is unavailable.

Sponsors and collaborators

Lead sponsor

Kirby Institute

Other Gov

Registry information

Official study title

A Phase III/IV Factorial Randomized Double-blind Trial to Compare the Addition of Dapagliflozin vs Placebo and Rosuvastatin/Ezetimibe Versus Pitavastatin in Patients With HIV on Integrase Strand Transfer Inhibitor-based Antiretrovirals With Elevated Metabolic Risk

Acronym: OPTIMAR

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
Mar 19, 2024
Registry last updated
Jul 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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