Screening for Asymptomatic Coronary Artery Disease in Kidney Transplant Candidates (CARSK)

Canadian-Australasian Randomised Trial of Screening Kidney Transplant Candidates for Coronary Artery Disease

The Canadian Australasian Randomized Trial of Screening Kidney Transplant Candidates for Coronary Artery Disease (CARSK) will test the hypothesis that eliminating the regular use of non-invasive screening tests for CAD AFTER waitlist activation is not inferior to regular (i.e., annual) screening for CAD during wait-listing for the prevention of Major Adverse Cardiac Events. Secondary analyses will assess the impact of screening on the rate of transplantation, and the relative cost-effectiveness of screening.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases; End Stage Renal Disease; Kidney Transplantation; Dialysis Related Complication
• Intervention / Treatment: Other: No screening; Other: Regular Screening

Detailed Description

Cardiovascular disease is the commonest cause of death while on the kidney transplant waiting list and after transplantation. Current standard care involves screening for coronary artery disease prior to waitlist entry, then every 1-2 years, according to perceived risk, until transplanted. The aim of screening is two-fold. Firstly to identify patients with asymptomatic coronary disease to enable either correction, by bypass surgery or angioplasty, or removal of the patient from the list, with the ultimate aim of preventing premature cardiovascular mortality at the time of, or soon after kidney transplantation. Secondly, from a societal perspective, to prevent mis-direction of scarce donor organs into recipients who experience early mortality. This current screening strategy is not evidence based, has substantial known and potential harms, and is very costly. Two major issues of uncertainty require addressing in sequence: (1) whether to periodically screen asymptomatic wait-listed patients for occult coronary artery disease; and (2) whether to revascularise coronary stenoses in asymptomatic patients prior to transplantation. The CARSK study seeks to address the first of these 2 issues.

CARSK aims to

1. Test the hypothesis that after screening for wait list entry, no further screening for coronary artery disease (CAD) is non-inferior to the current standard care which is screening all asymptomatic wait-listed patients for CAD at regular intervals.
2. Compare the benefits and costs of not screening versus regular CAD screening from a health system perspective.

• Study Type: Interventional
• Enrollment (Actual): 3306
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • University of British Columbia
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V8
      • Dalhousie University
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare
    • Kingston, Ontario, Canada
      • Kingston Health Science Centre
    • London, Ontario, Canada
      • London Health Science Centre
    • Ottawa, Ontario, Canada, K1H 7W9
      • The Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network
    • Toronto, Ontario, Canada
      • St Michael's Hospital
  • Quebec
    • Laval, Quebec, Canada
      • CHU de Quebec-Universite Laval's L'Hotel-Dieu de Quebec
    • Montreal, Quebec, Canada
      • McGill University Health Centre
    • Montreal, Quebec, Canada, H1T 2M4
      • University of Montreal, Maisonneuve-Rosemont Hospital
    • Montreal, Quebec, Canada
      • Universite de Montreal, Hopital Maisonneuve-Rosemont
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • St. Paul's Hospital, University of Saskatchewan
• Germany
  • Berlin, Germany
    • Charité Universitätsmedizin
• United Kingdom
  • Brighton, United Kingdom, BN2 1ES
    • Sussex Brighton R&D
  • Brixton, United Kingdom, SW9 8RR
    • King's College Hospital NHS Foundation Trust
  • Carshalton, United Kingdom, SM5 1AA
    • Epsom and St Helier University Hospitals NHS Trust
  • London, United Kingdom, E1 4UJ
    • Barts Health NHS Trust
  • London, United Kingdom
    • St George's University Hospital NHS Trust Foundation
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20052
      • The George Washington University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. adults aged 18 years of age or older
2. Dialysis-dependent kidney failure and currently being assessed for OR active on the kidney transplant waiting list
3. expected to require further screening for CAD prior to transplantation (by current standard of care);
4. able to give consent;
5. anticipated to undergo transplantation more than 12 months from date of enrolment

Exclusion Criteria:

1. patients with signs or symptoms suggestive of uncontrolled cardiac disease such as unstable coronary syndromes, decompensated heart failure, uncontrolled arrhythmia, and severe valvular heart disease;
2. patients who "on-hold" for transplantation due to a medical problem;
3. patients with other solid organ transplants;
4. multi-organ transplant candidates (e.g. kidney-pancreas transplant candidates);
5. patients with planned living donor transplant;
6. patients unable to give consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: No screening; No further screening for asymptomatic coronary artery disease after wait-list entry	Other: No screening; No further screening for asymptomatic coronary artery disease after wait-list entry
Active Comparator: Regular screening; Regular (yearly or 2nd yearly) screening for asymptomatic coronary artery disease after wait-list entry	Other: Regular Screening; Annual or second-yearly screening for asymptomatic coronary artery disease after wait-list entry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACE	Primary efficacy: major adverse cardiac event (MACE), defined as any of the following: cardiovascular death, myocardial infarction, emergency revascularisation, hospitalisation with unstable angina. The outcome will be assessed by: Notification to the transplant coordinators when patients are admitted in hospital (this is the usual standard of care in waitlisted patients).; The trial coordinator will gather electronic medical records, letters, procedure notes, and will fill in the relevant case record form on the REDCap database (managed by Sydney local health district). All data are encrypted and stored on servers at SLHD, where it is backed up.; Patients will be followed up 6-monthly (alternating by phone and clinic visits) where trial coordinators will discuss any hospitalisation with the patients.	The investigators will analyse time to first MACE event for the duration of the trial (60 months), depending on patient's date of transplant. Follow-up will be 12 months posttransplant. Maximum follow-up is 72 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death	Death due to any cause	Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
Emergency revascularisation	Urgent, symptom-driven revascularisation for coronary artery disease	Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
Stroke	Stroke	Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
Health related quality of life	health related quality of life as measured by EQ5D and/or KDQOL 36	Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
Time of wait-listing	Time off the wait-list	Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
Cost effectiveness	Economic evaluation of the cost effectiveness of the trial from a health system perspective. Data on resource use will be obtained in two ways. First through identification of tests, procedures and doctor's visits related to cardiac and renal management for all study participants from randomisation to study end as recorded in the patient diaries and trial case report forms. Second, Australian participants will have their records linked to the Admitted Patient Data Collection, Emergency Department Data Collection, and through Medicare for all Medicare Benefits Schedule (MBS) outpatient visits, procedures and the Pharmaceutical Benefits Scheme (PBS) for medicines.	The analysis will take place at the end of the study. This outcome will be followed up for 5 years.
Incidence of transplantation	incidence of transplantation between the two arms	Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
Incidence of permanent removal from wait list for cardiac causes	incidence of permanent removal from the wait list due to cardiac causes between the two arms	Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
Cancellation of transplantation due to coronary artery disease	incidence of cancellation of transplantation due to coronary artery disease	Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
Cardiovascular death	incidence of cardiovascular death	Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: University of Sydney
• Investigators: Principal Investigator: Jagbir Gill, MD, University of British Columbia

Publications and helpful links

General Publications

• Ying T, Gill J, Webster A, Kim SJ, Morton R, Klarenbach SW, Kelly P, Ramsay T, Knoll GA, Pilmore H, Hughes G, Herzog CA, Chadban S, Gill JS. Canadian-Australasian Randomised trial of screening kidney transplant candidates for coronary artery disease-A trial protocol for the CARSK study. Am Heart J. 2019 Aug;214:175-183. doi: 10.1016/j.ahj.2019.05.008. Epub 2019 May 22.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Estimated): January 26, 2028
• Study Completion (Estimated): January 26, 2028

Study Registration Dates

• First Submitted: September 5, 2018
• First Submitted That Met QC Criteria: September 13, 2018
• First Posted (Actual): September 17, 2018

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Pathological Conditions, Signs and Symptoms; Cardiovascular Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: H16-01335_CARSK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No