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

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

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).

Study Overview

• Status: Completed
• Conditions: HIV Infection; Coronary Heart Disease
• Intervention / Treatment: Drug: Pravastatin; Drug: Rosuvastatin

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 Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

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

Collaborators and Investigators

• Sponsor: Matthew Feinstein
• Investigators: Study Chair: Donald Lloyd-Jones, MD, Northwestern University

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ACTUAL): June 1, 2021
• Study Completion (ACTUAL): June 1, 2021

Study Registration Dates

• First Submitted: July 14, 2016
• First Submitted That Met QC Criteria: July 19, 2016
• First Posted (ESTIMATE): July 22, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 18, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Acute Coronary Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Pravastatin
• Other Study ID Numbers: CSC01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No