The Canadian Prevention of Renal and Cardiovascular Endpoints Trial

The pilot study is designed in two phases. The first phase is intended to provide data on some key points that need to be addressed prior to future funding applications to the CIHR and the NHLBI. These applications are currently tentatively planned for the fall of 2005. The second phase of the pilot study is intended to more completely establish the feasibility of successfully completing the full trial by examining the issue of contamination and the ability of the intervention to generate a difference between the groups with regard to use of efficacious therapies and control of modifiable risk factors, or intermediate variables on the causal pathway to the clinical end-points in the full-scale trial. The second phase will also address the need to describe the operation of the experimental intervention more thoroughly. Finally, the second phase of the pilot study will compare the randomized study groups with regard to short-term quality-of-life outcomes.

Phase1

• How long does it take to recruit 100 patients per study site?
• What recruitment strategies are most efficient?
• How do the baseline characteristics of those recruited compare to referred populations, and to the general population with CKD?
• How do the nephrologist and nurse work together to provide care to those in the intervention group?
• What is the nature of the care provided by the nurses and physicians to those in the intervention group?
• Is the study nurse able to manage the patient load?
• How much time and resources are needed to a) provide care, b) to carry out study measurements?
• Can health care resources used be measured for economic analysis?

Phase II

• What is the rate of loss to follow-up?
• What is the overall estimate of the primary outcome event rate?
• By one year of follow-up, what is the difference between the study groups in terms of:

• Protocol interventions used (estimates contamination)
• Proportion i) smoking; and proportion achieving ii) BP, iii) lipid, iv) diabetes, v) anemia, vi) acidosis, vii) mineral metabolism targets
• Quality of Life
• Satisfaction with care Randomized, parallel, two group, multicentre, clinical trial of people with CKD, with or without diabetes mellitus or proteinuria. The intention is to roll the pilot study into the full-scale trial if the pilot itself is deemed successful. A laboratory-based case finding method will be used preferentially to identify potential participants. This will be supplemented by practice-based case-finding approaches where necessary to ensure recruitment of a representative population. Randomization will be by a central computer-based telephone process. Stratification will be by center and presence of diabetes and proteinuria. The intervention consists of a protocol guided, multiple risk factor and chronic disease care model-like approach delivered by a trained nurse supported by a nephrologist and will be based in a nephrology clinic like setting.

Inclusion criteria

• Stratum 1 (expected about 50% of trial subjects): Diabetes mellitus (by clinical history with documented prior plasma glucose levels in the diabetic range, or on hypoglycemic medications) and CKD as documented by calculated (Cockroft-Gault equation) creatinine clearance between 25 and 60 mls/min/1.73m2 derived from the screening serum creatinine value and the next most recent known value from more than 2 weeks prior; OR

Stratum 2 (expected about 20% of trial subjects): Non-diabetic with CKD as defined for Stratum 1 and proteinuria of > 1g/L by dipstick in random urine at screening; OR

Stratum 3 (expected about 30% of trial subjects): Non-diabetic with CKD as defined for stratum 1, but without proteinuria as for stratum 2 at screening

Exclusion criteria

• Unwilling to provide informed consent
• Likely to die of any known existing disease within 6 months
• Recently unstable/advanced cardiovascular disease (MI or acute coronary syndrome, hospitalized heart failure, TIA or stroke, leg amputation or gangrene in past 6 months)
• Currently receiving active treatment for a malignant, neoplastic disease other than localized non-melanoma skin cancer
• Progressive kidney disease currently treated by immunotherapy
• Currently receiving dialysis or likely to do so within 6 months
• Current organ transplant recipient (or planned within 6 months)
• Currently receiving ongoing care for CKD, or cardiovascular disease, in a multiple intervention, disease management program.
• Currently enrolled in another interventional trial
• Residing in a location not amenable to follow up for the trial