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

PHASE3ACTIVE_NOT_RECRUITING

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.

Study details:

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.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Age 40-75 years and at least one of the following risk factors:
  2. BMI > 7% increase or > 5kg weight gain since INSTI commencement, or
  3. BMI ≥ 30 kg/m2
  4. BMI ≥18 kg/m2 prior to INSTI commencement
  5. Currently taking INSTI-based ART
  6. Sustained virologic response, defined as viral load <200 copies/mL for at least 12 months
  7. Current CD4 >250 cells/mm3
  8. 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.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE3

trial

Study ID

NCT06317051

Intervention or treatment

DRUG: Dapagliflozin 10mg Tab

DRUG: Pitavastatin 4 Mg Oral Tablet

DRUG: Rosuvastatin and Ezetimibe

DRUG: Placebo

Conditions

  • HIV Infections
  • Weight Gain

  • Condition: HIV Infections, Weight Gain

  • DRUG: Dapagliflozin 10mg Tab and other drugs

  • Sydney, New South Wales, Australia and more

  • Sponsor: Kirby Institute

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

St Vincent's Hospital

Select from list below to view details:

  • St Vincent's Hospital

    Sydney, New South Wales, Australia

  • Austin Health

    Melbourne, Victoria, Australia

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Who is running the clinical trial?

KI

Kirby Institute

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
ACTIVE_COMPARATOR: Dapagliflozin 10mg + pitavastatin 4mg
  • Dapagliflozin 10mg + pitavastatin 4mg given as daily tablets for 48 weeks
Drug: Dapagliflozin 10mg Tab, Drug: Pitavastatin 4 Mg Oral Tablet
    ACTIVE_COMPARATOR: Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg
    • Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg given as daily tablets for 48 weeks
    Drug: Dapagliflozin 10mg Tab, Drug: Rosuvastatin and Ezetimibe
      PLACEBO_COMPARATOR: Placebo + pitavastatin 4mg
      • Placebo + pitavastatin 4mg given as daily tablets for 48 weeks
      Drug: Pitavastatin 4 Mg Oral Tablet, Drug: Placebo
        PLACEBO_COMPARATOR: Placebo + rosuvastatin 10mg/ezetimibe 10mg
        • Placebo + rosuvastatin 10mg/ezetimibe 10mg given as daily tablets for 48 weeks
        Drug: Rosuvastatin and Ezetimibe, Drug: Placebo

          What is the study measuring?

          Primary Outcome

          MeasureDescriptionTime Frame
          To assess the impact of dapagliflozin vs. placebo on weight reductionMean 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) concentrationMean change in LDL as absolute change from baseline to 24 weeks across treatment arms24 weeks

          Secondary Outcome

          MeasureDescriptionTime Frame
          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^2Not Specified48 weeks
          To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on waist (cm) to hip (cm) ratioNot Specified48 weeks
          To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on waist (cm) to height (cm) ratioNot Specified48 weeks
          To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on systolic and diastolic blood pressure (mm Hg)Not Specified48 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.Not Specified48 weeks
          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)Not Specified48 weeks
          To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on fasting glucose (mmol/L)Not Specified48 weeks
          To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on haemoglobin A1C (%)Not Specified48 weeks
          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)Not Specified48 weeks
          To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on inflammatory biomarkers (tested centrally on stored research samples)Not Specified48 weeks
          To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on Serious adverse events.Not Specified48 weeks
          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)Not Specified48 weeks
          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.Not Specified48 weeks
          To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe from baseline to 48 weeks on inflammatory biomarkers (tested centrally on stored research samples)Not Specified48 weeks
          To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe from baseline to 48 weeks on serious adverse eventsNot Specified48 weeks
          Are you running this trial?If you're a clinic or sponsor, you can claim this study.
          Claim this trial

          References

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

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