High Intensity Lipid Lowering Following Acute Coronary Syndromes for Persons Living With HIV

Phase 2

Completed

Conditions: Coronary Heart Disease
HIV Infection

Interventions: Drug: Pravastatin
Drug: Rosuvastatin

Registration Number: NCT02841774

Lead Sponsor: Matthew Feinstein

Brief Summary: HILLCLIMBER is a randomized, controlled, open-label phase II trial of moderate dose statin therapy (pravastatin 40mg daily) versus high-dose statin therapy (rosuvastatin 20-40mg daily) in HIV-infected persons taking antiretroviral therapy (ART) who have coronary heart disease (CHD).

Detailed Description: HILLCLIMBER is a randomized, controlled, open-label phase II trial of moderate dose statin therapy versus high-dose statin therapy in HIV-infected persons taking antiretroviral therapy (ART) who have coronary heart disease (CHD).

All subjects will have an initial 2-week run-in period with pravastatin 40mg daily (Week 0 to 2). Subjects not demonstrating significant toxicity at week 2 will then be randomized to rosuvastatin 20mg (high intensity dose group) versus continuing pravastatin 40mg daily (moderate intensity group) for 12 weeks (Weeks 2 to 14). At week 6, those in the rosuvastatin arm who do not demonstrate significant toxicity and whose LDL-c is \>60mg/dl and decreased by less than 25% compared with week 2 will then have doses increased to rosuvastatin 40mg.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

Inclusion Criteria

HIV-1 infection
HIV RNA below the lower limit of assay detection within 12 months of study entry
1. Documented coronary heart disease (CHD): nonfatal MI, unrecognized MI, unstable angina pectoris, and/or stable angina pectoris, as defined by the American Heart Association Case Definitions for Acute Coronary Heart Disease in Epidemiology and Clinical Research Studies, OR Or (2) Documented 10-year ASCVD risk of 15% or greater based on the ACC/AHA ASCVD Risk Estimator
Negative serum or urine pregnancy test
Men and women age 18 to 75 years of age

Exclusion Criteria

Serious illness or AIDS-related complication within 21 days of screening requiring systemic treatment and/or hospitalization
No coronary heart disease (CHD) and 10-year ASCVD risk <15.0%.
Not currently receiving antiretroviral therapy or taking any of the following antiretroviral agents: atazanavir/ritonavir, lopinavir/ritonavir.
History of statin intolerance leading to discontinuation, dose decrease, or change to less potent dose equivalent
Statin absolute contraindication
Current use of atorvastatin 20mg daily or greater or rosuvastatin 10mg daily or greater
Chronic kidney disease stage 4 or greater (including dialysis)
Systolic heart failure with last documented LVEF <35%
Pregnant or breastfeeding
Laboratory values obtained within 45 days prior to study entry:

LDL-c <80 mg/dl while not on statin or LDL-c <60 mg/dl while on statin ALT > 3 x Upper Limit of Normal (ULN) AST > 3 x ULN Creatinine kinase (CK) >3 x ULN (calculated creatinine clearance (CrCl) <50 mL/min, as estimated by the Cockcroft-Gault equation)

Life expectancy <12 months
Prior organ transplant
Active malignancy
Inflammatory muscle disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Moderate Intensity Group	Pravastatin	pravastatin 40mg daily for 12 weeks
High Intensity Group	Rosuvastatin	rosuvastatin 20 - 40 mg daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Mean Percent Change in Fasting LDL-cholesterol	Week 2 and Week 14	Mean percent change in fasting LDL-cholesterol at Week 2 and Week 14
Treatment-emergent Adverse Events	14 weeks	Number of Grade 3 or above adverse events

Secondary Outcome Measures