ILLUMINATE Trial

High Density Lipoprotein Microchapters
Home
Patient information
Overview
Historical Perspective
Classification
Physiology
Pathophysiology
Causes Low HDL High HDL
Epidemiology and Demographics
Screening
Natural History, Complications and Prognosis
Diagnosis
HDL Laboratory Test
Treatment
Medical Therapy
Prevention
Future or Investigational Therapies
Clinical Trials
Landmark Trials
List of All Trials
Case Studies
Case #1
ILLUMINATE Trial On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of ILLUMINATE Trial All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on ILLUMINATE Trial
CDC on ILLUMINATE Trial
ILLUMINATE Trial in the news
Blogs on ILLUMINATE Trial
Directions to Hospitals Treating High density lipoprotein
Risk calculators and risk factors for ILLUMINATE Trial

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Objective

Raising HDL levels by a combination of torcetrapib, a CETP inhibitor, and atorvastatin, an HGM-CoA reductase inhibitor.

Timeline

Start Date

August 23, 2004

End Date

Premature Termination on December 2, 2006. Data collection continued till July 15, 2007.

Methods

• Phase III trial
• Prospective, randomized, multicenter, double-blind clinical trial that recuited 15,067 patients.
• Inclusion criteria: Patients aged 45-75 years who have a history of cardiovascular disease 30 days to 5 years before screening; patients who have type 2 diabetes mellitus that meet criteria of the American Diabetes Association or receive anti-diabetic agents, even without previous cardiovascular disease.
• Exclusion criteria: Unstable medical condition, life expectancy less than 5 years, LDL-C levels < 100 mg/dL, those not receiving anti-lipidemic medications, if LDL-C target level not achieved at termination of run-in period, and those who have cardiovascular event during run-in period or uncontrolled hypertension: SBP>140 mmHg or DBP>90 mmHg,
• Run-in period: 4-10 weeks
• Cardiovascular disease was defined as myocardial infarction, stroke, acute coronary syndrome, unstable angina, peripheral vascular disease, and cardiac revascularization.
• Two arms of the study: Atorvastatin alone or atorvastatin plus torcetrapib 60 mg. Dosage of atorvastatin was determined while achieving of target LDL-C levels during run-in period and can be changed during the study period according to LDL-C levels.
• Primary Outcome was defined as the time to first “cardiovascular event”.
• “Cardiovascular event” defined as death from coronary artery disease, nonfatal myocardial infarction, stroke, or hospitalization for unstable angina. Procedure-related deaths and events were excluded.
• Secondary outcome: time to the first occurrence of a primary outcome. Time to death regardless of the etiology, change from baseline LDL and HDL levels.
• Outcomes based on 1,3,6,9, and 12 months scheduled visits.

Results

• Median follow-up: 550 days
• Follow-up completion: 99.7% of patients
• Early discontinuation: 11% in atorvastatin group and 13.4% in torcetrapib group.
• One year follow-up showed increase of HDL (72.1%), a decrease of LDL (24.9%), and a decrease of 9% of triglycerides among patients on torcetrapib vs. minimal change in lipid profile in atorvastatin group (p<0.001).
• After 3 months follow-up, there was a small, but significant, change in CRP levels (p=0.01)
• After 12 months follow-up, blood pressure decrease was 0.9% in atorvastatin group vs. 5.4 mmHg in torcetrapib group (p<0.001). Torcetrapib group also have a 0.08 mmol/L decrease in potassium, a 1.39 mmol/L increase in sodium, and a 2.28 mmol/L increase in bicarbonate vs. an increase in all 3 among the atorvastatin group with electrolyte values increasing 0.06 mmol/L, 0.78 mmol/L, and 1.93 mmol/L, respectively (p<0.001)..
• In contrast, estimated glomerular filtration rate (eGFR) increased 0.8 ml/min/1.73m2 in torcetrapib group, but decreased 0.3 ml/min/1.73m2 in the atorvastatin group (p<0.001)
• QT interval changes after 12 months were 3.3 msec and 0.3 msec in torcetrapib and atorvastatin groups, respectively (p<0.001)
• Measurements of aldosterone showed that after 3 months, there was a significant increase in aldosterone measurements in the torcetrapib group among 85th, 90th, and 95th percentile values.

Study Outcomes

• Hazard ratio for death was 1.58 in torcetrapib group at the end of the study (p=0.006).
• Torcetrapib group had a 1.25 hazard ratio for primary outcomes (p=0.001), most notably significant for unstable angina (p=0.001) and least importanta for stroke (0.74).
• Significant increase in adverse events in torcetrapib group was reported: hypertension, peripheral edema, angina pectoris, dyspnea, and headache (p<0.001 – p=0.02).