Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults

• Status: Active, not recruiting
• Trial end date: 2023-03-26
• Target enrollment: 0
• Participant gender: All

Summary

People infected with HIV are at risk for cardiovascular disease (CVD). This study will evaluate the use of pitavastatin to reduce the risk of CVD in adults infected with HIV who are on antiretroviral therapy (ART).

The REPRIEVE trial consists of two parallel identical protocols:

• REPRIEVE (A5332) is funded by the NHLBI, with additional infrastructure support provided by the NIAID, and is conducted in U.S and select international sites (approximately 120 sites in 11 countries).

• REPRIEVE (EU5332) is co-sponsored by NEAT ID and MGH, and is conducted at 13 sites in Spain.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Gilead Sciences; Kowa Pharmaceuticals America, Inc.; Massachusetts General Hospital; National Heart, Lung, and Blood Institute (NHLBI); NEAT ID Foundation
• Treatments: Pitavastatin

Criteria

Inclusion Criteria:

• HIV-1 infected individuals

• Combination antiretroviral therapy (ART) for at least 180 days prior to study entry

• CD4+ cell count greater than 100 cells/mm^3

• Acceptable screening laboratories including a:

• Fasting low-density lipoprotein (LDL) cholesterol as follows: If ASCVD risk score is less than 7.5%, LDL cholesterol must be less than 190 mg/dL. If ASCVD risk score is greater than or equal to 7.5% and less than or equal to 10%, LDL must be less than 160 mg/dL. If ASCVD risk score is greater than 10% and less than or equal to 15%, LDL must be less than 130 mg/dL. NOTE: If LDL is less than 70 mg/dL, participant is eligible regardless of 10-year ASCVD risk score in line with the ACC/AHA 2013 Prevention Guidelines.

• Fasting triglycerides less than 500 mg/dL

• Hemoglobin greater than or equal to 8 g/dL for female participants and greater than or equal to 9 g/dL for male participants

• Glomerular filtration rate (GFR) greater than or equal to 60 mL/min/1.73m^2 or creatinine clearance (CrCl) greater than or equal to 60 mL/min

• Alanine aminotransferase (ALT) less than or equal to 2.5 x the upper limit of normal (ULN)

• For persons with known chronic active hepatitis B or C, calculated fibrosis 4 score (FIB-4) must be less than or equal to 3.25

• Ability and willingness of participant or legal representative to provide written informed consent

Exclusion Criteria:

• Clinical ASCVD, as defined by 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, including a previous diagnosis of any of the following:

• Acute myocardial infarction (AMI)

• Acute coronary syndromes

• Stable or unstable angina

• Coronary or other arterial revascularization

• Stroke

• Transient ischemic attack (TIA)

• Peripheral arterial disease presumed to be of atherosclerotic origin

• Current diabetes mellitus if LDL is greater than or equal to 70 mg/dL

• 10-year ASCVD risk score estimated by Pooled Cohort Equations greater than 15%

• Active cancer within 12 months prior to study entry.

• NOTE: Exceptions:

• Successfully treated non-melanomatous skin cancer

• Kaposi sarcoma without visceral organ involvement

• Known decompensated cirrhosis

• History of myositis or myopathy with active disease in the 180 days prior to study entry

• Known untreated symptomatic thyroid disease

• History of allergy or severe adverse reaction to statins

• Use of specific immunosuppressants or immunomodulatory agents including but not limited to tacrolimus, sirolimus, rapamycin, mycophenolate, cyclosporine, tumor necrosis factor (TNF)-alpha blockers or antagonists, azathioprine, interferon, growth factors, or intravenous immunoglobulin (IVIG) in the 30 days prior to study entry. NOTE: Use of oral prednisone less than or equal to 10 mg/day or equivalent dosage is allowed.

• Current use of erythromycin, colchicine, or rifampin

• Use of any statin drugs, gemfibrozil, or PCSK9 inhibitors in the 90 days prior to study entry

• Current use of an investigational new drug that would be contraindicated

• Serious illness or trauma requiring systemic treatment or hospitalization in the 30 days prior to study entry

• Current pregnancy or breastfeeding

• Alcohol or drug use that, in the opinion of the site investigator, would interfere with completion of study procedures

• Other medical, psychiatric, or psychological condition that, in the opinion of the site investigator, would interfere with completion of study procedures and or adherence to study drug