The Canadian Prevention of Renal and Cardiovascular Endpoints Trial

• Time to major cardiovascular event(myocardial infarction, stroke, coronary or peripheral revascularization, hospitalization for heart failure or unstable angina, or death due to cardiovascular cause)
• - Time to first major clinical event (ESRD, non-fatal cardiovascular events as in secondary (a) or all cause death)

• • # patients screened via lab
• • # patients seen meeting eligibility criteria
• • # patients enrolled over documented period
• • OR similar assessment of the success of recruitment if non-laboratory based
• • Description of baseline characteristics including care in place at study entry to compare to existing databases on clinic patients and community data
• • Description of how the intervention is applied (by chart review, interviews and activity records)
• • Assessment of the workload and study staff requirements
• • The % of patients having a cardiovascular or kidney related clinical outcome event by one and two years of study
• • The % of patients lost to follow-up each year from the experimental and control groups
• • The % of patients in the experimental and control groups achieving targets for blood pressure, lipids, diabetes control, anemia, and mineral metabolism at six months, one and two years.
• • The % of patients in the experimental and control groups smoking at six months, one and two years.
• • The quality of life of those in the experimental and control groups at baseline, six, twelve and 24 months.
• • The satisfaction with care received in the experimental and control groups

Advanced kidney disease with it's associated heart and blood vessel problems are becoming more frequent. These problems markedly affect length and quality of life and cost a lot to treat. Treatments are known that can prevent development of advanced kidney and heart disease. These treatments are not being optimally applied in the current health system. This study aims to identify people with relatively early stage chronic kdiney disease. With the participation of these people, the study will test whether a nurse co-ordinated clinic involving a medical kidney specialist, applying the known treatments, can reduce or delay the onset of advanced kidney disease and heart and blood vessel problems such as heart attack, stroke and death, to a greater extent than usual care. The study will also address issues of costs associated with care and illness. The nature of the care provided by the heatlh care professionals will be studied to see how best to achieve good health outcomes.

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

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

Phase II

1. What is the rate of loss to follow-up?
2. What is the overall estimate of the primary outcome event rate?

3. By one year of follow-up, what is the difference between the study groups in terms of:

   1. Protocol interventions used (estimates contamination)
   2. Proportion i) smoking; and proportion achieving ii) BP, iii) lipid, iv) diabetes, v) anemia, vi) acidosis, vii) mineral metabolism targets
   3. Quality of Life
   4. Satisfaction with care andomized, 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.

• Procedure: Combined CKD and CVD Prevention
• Procedure: Cardiovascular Disease prevention
• Procedure: Treatment of Chronic Kidney Disease complications

• Hopkins RB, Garg AX, Levin A, Molzahn A, Rigatto C, Singer J, Soltys G, Soroka S, Parfrey PS, Barrett BJ, Goeree R. Cost-effectiveness analysis of a randomized trial comparing care models for chronic kidney disease. Clin J Am Soc Nephrol. 2011 Jun;6(6):1248-57. Epub 2011 May 26.
• Barrett BJ, Garg AX, Goeree R, Levin A, Molzahn A, Rigatto C, Singer J, Soltys G, Soroka S, Ayers D, Parfrey PS. A nurse-coordinated model of care versus usual care for stage 3/4 chronic kidney disease in the community: a randomized controlled trial. Clin J Am Soc Nephrol. 2011 Jun;6(6):1241-7. Epub 2011 May 26.

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

• Canadian Institutes of Health Research (CIHR)
• Canadian Diabetes Association
• The Kidney Foundation of Canada
• Heart and Stroke Foundation
• Merck Frosst Canada Ltd.
• Amgen
• Janssen-Ortho Inc., Canada