The Canadian ACE-inhibitor trial to improve renal outcomes and patient survival in kidney transplantation--study design.
BACKGROUND
In non-transplant patients with chronic kidney disease and proteinuria, inhibition of the renin-angiotensin system with an ACE-inhibitor or an angiotensin receptor blocker has been shown to delay the progression of renal disease. Observational studies in the kidney transplant population have produced conflicting results with some studies showing benefit and others no benefit of renin-angiotensin system blockade.


METHODS
This report describes the design and methodological issues of a randomized controlled trial evaluating the effect of ramipril in a renal transplant population. This study has been funded by a peer-reviewed grant from the Canadian Institutes of Health Research and is registered on the International Standard Randomised Controlled Trial Number Registry (ISRCTN-78129473).


RESULTS
The study will randomize 528 kidney transplant patients (11 Canadian centers) with proteinuria and an estimated GFR between 20 and 55 ml/min/1.73 m(2) to either ramipril (5 mg BID) or placebo. Patients, clinical staff and investigators will be blinded to treatment allocation. The primary outcome will be a composite measure incorporating doubling of serum creatinine, end stage renal disease or death. Principal secondary outcomes include: decline in GFR using a radioisotopic method, change in proteinuria, change in blood pressure, incidence of adverse events (e.g. hyperkalemia, anemia), incidence of cardiovascular events and health-related quality of life assessed by the Short Form-36 and the EuroQol-5D.


CONCLUSIONS
Upon completion, this trial will provide clinically meaningful evidence about whether treatment with an ACE-inhibitor will reduce patient mortality and prolong allograft survival in renal transplant recipients.
Knoll
Greg A
GA
Division of Nephrology, Kidney Research Center, Ottawa Health Research Institute, Ottawa, Ontario, Canada. gknoll@ottawahospital.on.ca
Cantarovitch
Marcelo
M
Cole
Ed
E
Gill
John
J
Gourishankar
Sita
S
Holland
Dave
D
Kiberd
Bryce
B
Muirhead
Norman
N
Prasad
Ramesh
R
Tibbles
Lee Anne
LA
Treleaven
Darin
D
Fergusson
Dean
D
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000401:mortality* / Q000601:surgery; D016030:Kidney Transplantation; D011446:Prospective Studies; D017257:Ramipril / Q000627:therapeutic use*; D012107:Research Design; D015996:Survival Rate
D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril