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

Sponsor

Matthew Feinstein (Other)

Overall Status

Completed

CT.gov ID

NCT02841774

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
HIV Infection Coronary Heart Disease	Drug: Pravastatin Drug: Rosuvastatin	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 1, 2016

Actual Primary Completion Date :

Jun 1, 2021

Actual Study Completion Date :

Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Moderate Intensity Group pravastatin 40mg daily for 12 weeks	Drug: Pravastatin 40mg daily (Weeks 2 - 14)
Experimental: High Intensity Group rosuvastatin 20 - 40 mg daily for 12 weeks	Drug: Rosuvastatin 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 Other Names: CRESTOR

Arm

Intervention/Treatment

Active Comparator: Moderate Intensity Group

pravastatin 40mg daily for 12 weeks

Drug: Pravastatin

40mg daily (Weeks 2 - 14)

Experimental: High Intensity Group

rosuvastatin 20 - 40 mg daily for 12 weeks

Drug: Rosuvastatin

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

Other Names:

CRESTOR

Outcome Measures

Primary Outcome Measures

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

Mean percent change in fasting HDL-cholesterol [Week 2 and Week 14]
Mean percent change in fasting HDL-cholesterol at Week 2 and Week 14
Mean percent change in fasting Total Cholesterol [Week 2 and Week 14]
Mean percent change in fasting Total Cholesterol at Week 2 and Week 14
Mean percent change in fasting Triglycerides [Week 2 and Week 14]
Mean percent change in fasting Triglycerides at Week 2 and Week 14

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)