Clinical trial NCT03674307: Screening for Asymptomatic Coronary Artery Disease in Kidney Transplant Candidates
Official title: Canadian-Australasian Randomised Trial of Screening Kidney Transplant Candidates for Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cardiovascular Diseases
End Stage Renal Disease
Kidney Transplantation
Dialysis Related Complication
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: University of Sydney
First posted: 2018-09-17
Enrollment: 3306
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: MACE
timeFrame: 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 outcomes:
measure: All-cause death
timeFrame: Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
measure: Emergency revascularisation
timeFrame: Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
measure: Stroke
timeFrame: Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
measure: Health related quality of life
timeFrame: Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
measure: Time of wait-listing
timeFrame: Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
measure: Cost effectiveness
timeFrame: The analysis will take place at the end of the study. This outcome will be followed up for 5 years.
measure: Incidence of transplantation
timeFrame: Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
measure: Incidence of permanent removal from wait list for cardiac causes
timeFrame: Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
measure: Cancellation of transplantation due to coronary artery disease
timeFrame: Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
measure: Cardiovascular death
timeFrame: Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Washington
country: United States
facility: The George Washington University
state: District of Columbia
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Halifax
country: Canada
facility: Dalhousie University
state: Nova Scotia
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Science Centre
state: Ontario
city: London
country: Canada
facility: London Health Science Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
city: Laval
country: Canada
facility: CHU de Quebec-Universite Laval's L'Hotel-Dieu de Quebec
state: Quebec
city: Montréal
country: Canada
facility: University of Montreal, Maisonneuve-Rosemont Hospital
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Montréal
country: Canada
facility: Universite de Montreal, Hopital Maisonneuve-Rosemont
state: Quebec
city: Saskatoon
country: Canada
facility: St. Paul's Hospital, University of Saskatchewan
state: Saskatchewan
city: Berlin
country: Germany
facility: Charité Universitätsmedizin
city: Brighton
country: United Kingdom
facility: Sussex Brighton R&D
city: Brixton
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: Carshalton
country: United Kingdom
facility: Epsom and St Helier University Hospitals NHS Trust
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: St George's University Hospital NHS Trust Foundation
Study officials:
affiliation: University of British Columbia
name: Jagbir Gill, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.