Screening for Asymptomatic Coronary Artery Disease in Kidney Transplant Candidates

Cardiovascular Diseases Clinical Trial

— CARSK  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03674307
• Other study ID #: H16-01335_CARSK
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2018
• Est. completion date: December 31, 2023

Study information

• Verified date: November 2022
• Source: University of British Columbia
• Contact: Angela Ogniben
• Phone: 1-604-682-2344
• Email: aogniben[@]providencehealth.bc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3306
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Coronary Artery Disease
• Coronary Disease
• Dialysis Related Complication
• End Stage Renal Disease
• Kidney Failure, Chronic
• Kidney Transplantation
• Myocardial Ischemia

Intervention

Other:
• No screening
No further screening for asymptomatic coronary artery disease after wait-list entry
• Regular Screening
Annual or second-yearly screening for asymptomatic coronary artery disease after wait-list entry

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta
Canada	Dalhousie University	Halifax	Nova Scotia
Canada	St. Joseph's Healthcare	Hamilton	Ontario
Canada	Kingston Health Science Centre	Kingston	Ontario
Canada	CHU de Quebec-Universite Laval's L'Hotel-Dieu de Quebec	Laval	Quebec
Canada	London Health Science Centre	London	Ontario
Canada	McGill University Health Centre	Montréal	Quebec
Canada	Universite de Montreal, Hopital Maisonneuve-Rosemont	Montréal	Quebec
Canada	University of Montreal, Maisonneuve-Rosemont Hospital	Montréal	Quebec
Canada	The Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	St. Paul's Hospital, University of Saskatchewan	Saskatoon	Saskatchewan
Canada	St Michael's Hospital	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia
Germany	Charité Universitätsmedizin	Berlin
United Kingdom	Sussex Brighton R&D	Brighton
United Kingdom	King's College Hospital NHS Foundation Trust	Brixton
United Kingdom	Epsom and St Helier University Hospitals NHS Trust	Carshalton
United Kingdom	Barts Health NHS Trust	London
United Kingdom	St George's University Hospital NHS Trust Foundation	London
United States	University of Arizona	Tucson	Arizona
United States	The George Washington University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University of British Columbia	University of Sydney

Countries where clinical trial is conducted

United States,  Canada,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Stroke	Stroke	Between 24 and 72 months, depending on patient's date of transplant. Follow-up will be 12 months posttransplant
Secondary	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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