Clinical trial NCT02082483: Coronary Artery Disease Screening in Kidney Transplant Candidates
Official title: Pilot Study to Determine Feasibility of a Randomized Trial of Screening for Coronary Artery Disease in Kidney Transplant Candidates
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End Stage Renal Disease
Coronary Artery Disease
Keywords: Kidney Transplant
Screening
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2014-03-10
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Kidney transplant candidates are at very high risk for coronary artery disease (CAD). The optimal strategy to monitor and maintain the cardiac fitness of patients awaiting kidney transplantation is unknown. Currently patients undergo annual testing; however, screening for CAD may increase morbidity and mortality by:

1. exposing patients to the risk of angiography and revascularization procedures
2. delaying or excluding patients from life saving transplantation.

Before proceeding with a definitive study to determine whether screening is necessary, feasibility will be determined in this pilot study.

Detailed description: This pilot trial will determine the feasibility of a multi-center, randomized, parallel group definitive trial. Asymptomatic wait-listed patients will be randomized to routine screening for coronary artery disease (CAD) (i.e. Myocardial Perfusion Scintigraphy (MPS) or Dobutamine Stress Echo (DSE)) as per the current standard of care versus selective screening based on symptoms. Patients enrolled in the pilot will be included in the definitive trial analysis. The pilot trial will include four Canadian centres. The definitive trial will aim to determine if a strategy of selective use of screening tests (i.e. Myocardial Perfusion Scintigraphy or Dobutamine Stress Echo) only in the presence of symptoms (i.e. chest pain, dyspnea etc) is non-inferior with respect to the composite endpoint of non-fatal MI and cardiac death compared to screening all asymptomatic wait-listed patients at regular intervals as described in transplant specific guidelines published by the National Kidney Foundation.

Currently there is no strong evidence for or against using routine cardiac screening of asymptomatic transplant patients, more evidence based randomized clinical trials are needed. This need is further highlighted by a number of factors such as: wait-listed patients are increasing in number and medical complexity; longer wait times and changing donor characteristics can increase CAD risk; wait-listed patients are at high risk for CAD but are commonly asymptomatic; the standard of care is not evidence based and is expensive; the current standard may be harmful. The study will determine feasibility of a definitive trial through the measures outlined under 'Outcome Measures'.

End stage renal disease (ESRD) patients wait-listed for kidney transplantation will be randomized to undergo selective screening for CAD, in which patients are only screened if they develop symptoms suggestive of CAD or the current standard of care that involves regular screening for CAD at fixed time intervals based on the presence of risk factors. Patients will remain on the pilot trial protocol until death, non-fatal MI, transplantation, permanent removal from the waiting list for any reason, or 24 months after enrolment in the pilot trial. During wait-listing, follow-up telephone interviews and chart reviews will be performed every six months. After transplantation, an in-person follow up visit and chart review will occur at the time of discharge from hospital, and a telephone interview and chart review will be performed 3 months after transplantation. Patients will be followed for 24 months from the date of enrolment. Patients who receive a kidney transplant during the study will be followed for 27 months.

For the pilot trial, descriptive analyses are planned. Feasibility will be summarized with proportions, rates, means, and medians as appropriate. Comparison of the definitive trial outcomes between treatment groups, will not be done at the end of the internal pilot as these patients will be included in the definitive trial. Analyses of enrolment rates and consent rates will be done after the enrolment phase of the pilot trial in late 2014. An interim analysis of protocol adherence is planned in mid 2016 in support of the definitive trial funding application in September, 2016.

Eligibility criteria: Inclusion Criteria:

* age greater than 18 years
* active on the deceased donor transplant waiting list

Exclusion Criteria:

* patients not expected to require further screening for CAD prior to transplantation by the current standard of care. For example, a diabetic patient recently screened for CAD and expected to be transplanted \<12 months from the start of the study would not require further screening according to current guidelines and would be ineligible
* patients with signs or symptoms suggestive of active cardiac disease such as unstable coronary syndromes, de-compensated heart failure, uncontrolled arrhythmia, and severe valvular heart disease
* patient who have been put "on hold" for transplantation due to a medical problem (e.g. an infection)
* prior extra-renal transplant recipients
* multi-organ transplant candidates (e.g. kidney pancreas transplant candidates)
* patients with a planned living donor transplant
* patients unable to provide informed consent

Primary outcomes:
measure: Number of Participants Adhering to the Expected Number of Screening Tests
timeFrame: Up to 27 months
measure: Enrolment Rates
timeFrame: Measured after enrolment period of 6 months
measure: Consent Rate
timeFrame: Measured after enrolment period of 6 months
Secondary outcomes:
measure: Number of Participants With Cardiac Events
timeFrame: Up to 27 months
Other outcomes:
measure: Number of Participants With Transplant Events
timeFrame: Up to 24 months
measure: Number of Participants With Wait List Holds or Removals
timeFrame: Up to 24 months
measure: Number of Health Care Encounters
timeFrame: Up to 27 months
Locations:
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
Study officials:
affiliation: St. Paul's Hospital
name: John Gill, MD
role: PRINCIPAL_INVESTIGATOR
References: