Rationale and design of dal-PLAQUE: a study assessing efficacy and safety of dalcetrapib on progression or regression of atherosclerosis using magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography/computed tomography

Am Heart J. 2011 Aug;162(2):214-221.e2. doi: 10.1016/j.ahj.2011.05.006.

Abstract

dal-PLAQUE is a placebo-controlled multicenter study designed to assess the effect of dalcetrapib on imaging measures of plaque inflammation and plaque burden. dal-PLAQUE is a multimodality imaging study in the context of the large dal-HEART Program. Decreased high-density lipoprotein cholesterol is linked to increased risk of coronary heart disease (CHD). Dalcetrapib, a compound that increases high-density lipoprotein cholesterol by modulating cholesteryl ester transfer protein, is being studied to assess if it can reduce the progression of atherosclerotic disease and thereby decrease cardiovascular morbidity and mortality. Patients with CHD or CHD-risk equivalents were randomized to receive 600 mg dalcetrapib or placebo daily for 24 months, in addition to conventional lipid-lowering medication and other medications for cardiovascular risk factors. The primary outcomes are the effect of dalcetrapib on 18F-fluorodeoxyglucose positron emission tomography target-to-background ratio after 6 months and magnetic resonance imaging (MRI) plaque burden (wall area, wall thickness, total vessel area, and wall area/total vessel area ratio) after 12 months. Secondary objectives include positron emission tomography target-to-background ratio at 3 months and MRI plaque burden at 6 and 24 months; plaque composition at 6, 12, and 24 months; and aortic compliance at 6 months. A tertiary objective is to examine the dynamic contrast-enhanced MRI parameters of plaque neovascularization. In total, 189 subjects entered screening, and 130 were randomized. dal-PLAQUE will provide important information on the effects of dalcetrapib on markers of inflammation and atherosclerotic plaque burden and, thereby, on the safety of cholesteryl ester transfer protein modulation with dalcetrapib. Results are expected in 2011.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amides
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / therapeutic use
  • Coronary Disease / diagnosis
  • Coronary Disease / drug therapy*
  • Diagnosis, Differential
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Esters
  • Female
  • Fluorodeoxyglucose F18*
  • Follow-Up Studies
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / diagnosis
  • Plaque, Atherosclerotic / drug therapy*
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals
  • Retrospective Studies
  • Risk Factors
  • Sulfhydryl Compounds / administration & dosage
  • Sulfhydryl Compounds / therapeutic use*
  • Tomography, X-Ray Computed / methods*
  • Treatment Outcome
  • Young Adult

Substances

  • Amides
  • Anticholesteremic Agents
  • Esters
  • Radiopharmaceuticals
  • Sulfhydryl Compounds
  • Fluorodeoxyglucose F18
  • dalcetrapib