Clinical trial NCT02841774: High Intensity Lipid Lowering Following Acute Coronary Syndromes for Persons Living With HIV
Official title: High Intensity Lipid Lowering Following Acute Coronary Syndromes for Persons Living With Human Immunodeficiency Virus (HILLCLIMBER)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infection
Coronary Heart Disease
Lead sponsor: Northwestern University
Sponsor class: OTHER
First posted: 2016-07-22
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mean Percent Change in Fasting LDL-cholesterol
timeFrame: Week 2 and Week 14
measure: Treatment-emergent Adverse Events
timeFrame: 14 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern University
name: Donald Lloyd-Jones, MD
role: STUDY_CHAIR
References: