Effect of serial infusions of reconstituted high-density lipoprotein (CER-001) on coronary atherosclerosis: rationale and design of the CARAT study.
BACKGROUND
High-density lipoprotein (HDL) is believed to have atheroprotective properties, but an effective HDL-based therapy remains elusive. Early studies have suggested that infusion of reconstituted HDL promotes reverse cholesterol transport and vascular reactivity. The CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial (CARAT) is investigating the impact of infusing an engineered pre-beta HDL mimetic containing sphingomyelin (SM) and dipalmitoyl phosphatidlyglycerol (CER-001) on coronary atheroma volume in patients with a recent acute coronary syndrome (ACS).


METHODS
The CARAT is a phase 2, multicenter trial in which 292 patients with an ACS undergoing intracoronary ultrasonography and showing percent atheroma volume (PAV) greater than 30% are randomly assigned to treatment with ten infusions of CER-001 3 mg/kg or matching placebo, administered at weekly intervals. Intracoronary ultrasonography is repeated at the end of the treatment period.


RESULTS
The primary endpoint is the nominal change in PAV. Safety and tolerability will also be evaluated.


CONCLUSIONS
CARAT will establish whether serial 3 mg/kg infusions of an engineered pre-beta HDL mimetic containing SM and dipalmitoyl phosphatidlyglycerol (CER-001) will regress atherosclerotic plaque in patients with a recent ACS.
South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
Jordan
J
Andrews
South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
Alex
A
Janssan
South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
Tracy
T
Nguyen
South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
Anthony D
AD
Pisaniello
South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
Daniel J
DJ
Scherer
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
John J P
JJ
Kastelein
Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
Bela
B
Merkely
Cleveland Clinic, Cleveland, Ohio, USA.
Steven E
SE
Nissen
School of Public Health, Imperial College London, London, UK.
Kausik
K
Ray
University of Colorado School of Medicine, Denver, CO, USA.
Gregory G
GG
Schwartz
South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
Stephen G
SG
Worthley
Cerenis Pharmaceuticals, Toulouse, France.
Connie
C
Keyserling
Cerenis Pharmaceuticals, Toulouse, France.
Jean-Louis
JL
Dasseux
South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
Julie
J
Butters
South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
Jacinta
J
Girardi
South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
Rosemary
R
Miller
South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
Stephen J
SJ
Nicholls
Atherosclerosis; CER-001; clinical trial; high-density lipoproteins (HDLs); intravascular ultrasound