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

HIV Infections Clinical Trial

— OPTIMAR  

Official 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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06317051
• Other study ID #: OPTIMAR
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: August 2024
• Est. completion date: December 2026

Study information

• Verified date: March 2024
• Source: Kirby Institute
• Contact: Hila Haskelberg, PhD
• Phone: +61 2 9348 1607
• Email: hhaskelberg[@]kirby.unsw.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: December 2026
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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. 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.

Related Conditions & MeSH terms

• HIV Infections
• Weight Gain

Intervention

Drug:
• Dapagliflozin 10mg Tab
Dapagliflozin will be administered as a comparator to the placebo to assess its effects on weight reduction
• 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
• 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
• Placebo
The placebo tablets are visually identical to the active drug tablets and will be administered as a comparator to Dapagliflozin.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Kirby Institute

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on waist (cm) to hip (cm) ratio		48 weeks
Secondary	To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on waist (cm) to height (cm) ratio		48 weeks
Secondary	To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on systolic and diastolic blood pressure (mm Hg)		48 weeks
Secondary	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
Secondary	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)		48 weeks
Secondary	To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on fasting glucose (mmol/L)		48 weeks
Secondary	To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on haemoglobin A1C (%)		48 weeks
Secondary	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)		48 weeks
Secondary	To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on inflammatory biomarkers (tested centrally on stored research samples)		48 weeks
Secondary	To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on Serious adverse events.		48 weeks
Secondary	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)		48 weeks
Secondary	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.		48 weeks
Secondary	To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe from baseline to 48 weeks on inflammatory biomarkers (tested centrally on stored research samples)		48 weeks
Secondary	To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe from baseline to 48 weeks on serious adverse events		48 weeks