Screening for Asymptomatic Coronary Artery Disease in Kidney Transplant Candidates

Study Overview
=================
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 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.

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

Conditions
-----------------
Cardiovascular Diseases, End Stage Renal Disease, Kidney Transplantation, Dialysis Related Complication

Intervention / Treatment
-----------------
* Other: No screening
* Other: Regular Screening


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

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 |