Coronary Heart Disease, HIV Infection
Conditions
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.
Interventions
DRUGPravastatin
40mg daily (Weeks 2 - 14)
DRUGRosuvastatin
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
Sponsors
Matthew Feinstein
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Moderate Intensity Group pravastatin 40mg daily for 12 weeks
Pravastatin: 40mg daily (Weeks 2 - 14) | 6 |
| High Intensity Group rosuvastatin 20 - 40 mg daily for 12 weeks
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 | 4 |
| Total | 10 |
Baseline characteristics
| Characteristic | Moderate Intensity Group | High Intensity Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 7 Participants |
| Region of Enrollment United States | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 0 / 6 | 0 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 4 |
Outcome results
Primary
Mean Percent Change in Fasting LDL-cholesterol
Mean percent change in fasting LDL-cholesterol at Week 2 and Week 14
Time frame: Week 2 and Week 14
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Moderate Intensity Group | Mean Percent Change in Fasting LDL-cholesterol | 15.0 Percent decrease |
| High Intensity Group | Mean Percent Change in Fasting LDL-cholesterol | 41.6 Percent decrease |
Primary
Treatment-emergent Adverse Events
Number of Grade 3 or above adverse events
Time frame: 14 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Intensity Group | Treatment-emergent Adverse Events | 0 Participants |
| High Intensity Group | Treatment-emergent Adverse Events | 0 Participants |