CARSK: Screening for Asymptomatic Coronary Artery Disease in Kidney Transplant Candidates

Sponsor

University of British Columbia (Other)

Overall Status

Recruiting

CT.gov ID

NCT03674307

Collaborator

University of Sydney (Other)

3,306

Enrollment

Locations

Arms

Anticipated Duration (Months)

194.5

Patients Per Site

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Diseases End Stage Renal Disease Kidney Transplantation Dialysis Related Complication	Other: No screening Other: Regular Screening	N/A

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

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.
Compare the benefits and costs of not screening versus regular CAD screening from a health system perspective.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

3306 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Screening

Official Title:

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

Actual Study Start Date :

Dec 1, 2018

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

MACE [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.]
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.

Secondary Outcome Measures

All-cause death [Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant]
Death due to any cause
Emergency revascularisation [Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant]
Urgent, symptom-driven revascularisation for coronary artery disease
Stroke [Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant]
Stroke
Health related quality of life [Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant]
health related quality of life as measured by EQ5D and/or KDQOL 36
Time of wait-listing [Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant]
Time off the wait-list
Cost effectiveness [The analysis will take place at the end of the study. This outcome will be followed up for 5 years.]
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.
Incidence of transplantation [Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant]
incidence of transplantation between the two arms
Incidence of permanent removal from wait list for cardiac causes [Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant]
incidence of permanent removal from the wait list due to cardiac causes between the two arms
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]
incidence of cancellation of transplantation due to coronary artery disease
Cardiovascular death [Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant]
incidence of cardiovascular death

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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;
patients who "on-hold" for transplantation due to a medical problem;
patients with other solid organ transplants;
multi-organ transplant candidates (e.g. kidney-pancreas transplant candidates);
patients with planned living donor transplant;
patients unable to give consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The George Washington University	Washington	District of Columbia	United States	20052
2	University of Alberta	Edmonton	Alberta	Canada
3	University of British Columbia	Vancouver	British Columbia	Canada	V6Z 1Y6
4	Dalhousie University	Halifax	Nova Scotia	Canada	B3H 1V8
5	St. Joseph's Healthcare	Hamilton	Ontario	Canada	L8N 4A6
6	Kingston Health Science Centre	Kingston	Ontario	Canada
7	London Health Science Centre	London	Ontario	Canada
8	The Ottawa Hospital Research Institute	Ottawa	Ontario	Canada	K1H 7W9
9	University Health Network	Toronto	Ontario	Canada	M5G 2N2
10	St Michael's Hospital	Toronto	Ontario	Canada
11	CHU de Quebec-Universite Laval's L'Hotel-Dieu de Quebec	Laval	Quebec	Canada
12	University of Montreal, Maisonneuve-Rosemont Hospital	Montréal	Quebec	Canada	H1T 2M4
13	McGill University Health Centre	Montréal	Quebec	Canada
14	Universite de Montreal, Hopital Maisonneuve-Rosemont	Montréal	Quebec	Canada
15	St. Paul's Hospital, University of Saskatchewan	Saskatoon	Saskatchewan	Canada
16	Charité Universitätsmedizin	Berlin		Germany
17	St George's University Hospital NHS Trust Foundation	London		United Kingdom