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

Study Overview
=================
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.

Official Title
-----------------
High Intensity Lipid Lowering Following Acute Coronary Syndromes for Persons Living With Human Immunodeficiency Virus (HILLCLIMBER)

Conditions
-----------------
HIV Infection, Coronary Heart Disease

Intervention / Treatment
-----------------
* Drug: Pravastatin
* Drug: Rosuvastatin


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Moderate Intensity Group<br>pravastatin 40mg daily for 12 weeks | Drug: Pravastatin<br>* 40mg daily (Weeks 2 - 14)<br>|
| Experimental: High Intensity Group<br>rosuvastatin 20 - 40 mg daily for 12 weeks | Drug: Rosuvastatin<br>* 20mg daily (Weeks 2 - 14); at Week 6, if AST, AST, and CK <+1.5 x ULN, and LDL-c is >60 and decreased by less than 25% compared with week 2, then dose will be increased to rosuvastatin 40mg daily<br>* Other names: CRESTOR;|

What is the study measuring?
-----------------
Primary Outcome Measures

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