Rationale and design of dal-VESSEL: a study to assess the safety and efficacy of dalcetrapib on endothelial function using brachial artery flow-mediated vasodilatation.
OBJECTIVE
Dalcetrapib increases high-density lipoprotein cholesterol (HDL-C) levels through effects on cholesteryl ester transfer protein (CETP). As part of the dalcetrapib dal-HEART clinical trial programme, the efficacy and safety of dalcetrapib is assessed in coronary heart disease (CHD) patients in the dal-VESSEL study (ClinicalTrials.gov identifier: NCT00655538), the design and methods of which are presented here. RESEARCH DESIGN AND STUDY METHOD: Men and women with CHD or CHD risk equivalent, with HDL-C levels <50  mg/dL were recruited for a 36-week, double-blinded, placebo-controlled trial. After a pre-randomisation phase of up to 8 weeks, patients received dalcetrapib 600  mg/day or placebo in addition to their existing treatments. Brachial flow-mediated dilatation (FMD) measured by B-mode ultrasound represents endothelial function and is a validated marker for early atherosclerosis and cardiovascular disease risk.


METHODS
The primary efficacy outcome is change from baseline in brachial FMD after 12 weeks. The primary safety endpoint is 24-hour ambulatory blood pressure monitoring (ABPM) assessed at week 4. Secondary endpoints include brachial FMD at 36 weeks, ABPM at 12 and 36 weeks, lipid profile, CETP mass and activity, and markers of inflammation, oxidation, and cardiovascular risk. Clinical endpoints are assessed as a composite endpoint for the dal-HEART Program.


RESULTS
In 19 European clinical centres, 476 subjects met inclusion criteria and have entered the study. In conclusion, the dal-VESSEL study is the largest multicentre trial with brachial FMD ever performed. The study assesses efficacy and safety of dalcetrapib on endothelial function, blood pressure, lipids, and clinical outcomes in CHD patients with below average HDL-C and will therefore provide vital information regarding its potential role in the preventative treatment of CHD risk.
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. j.j.kastelein@amc.uva.nl
John J P
JJ
Kastelein
Raphaël
R
Duivenvoorden
John
J
Deanfield
Eric
E
de Groot
J Wouter
JW
Jukema
Juan-Carlos
JC
Kaski
Thomas
T
Münzel
Stefano
S
Taddei
Valerie
V
Lehnert
Tracy
T
Burgess
David
D
Kallend
Thomas F
TF
Lüscher
D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D000577:Amides; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001916:Brachial Artery / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004952:Esters; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010919:Placebos; D011908:Rationalization; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D012107:Research Design; D013438:Sulfhydryl Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
D000577:Amides; D000924:Anticholesteremic Agents; D004952:Esters; D010919:Placebos; D013438:Sulfhydryl Compounds; C411602:dalcetrapib