Del Nido Cardioplegia Randomized Trial

Study Overview
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Brief Summary
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The use of a modified depolarizing cardioplegia solution in adult cardiac surgery would allow for prolonged re-dosing intervals while providing equivalent myocardial protection. The use of del Nido solution has been used extensively in congenital heart surgery for over 25 years. The primary objective is to determine whether expanding this technique to adult cardiac surgery will confer significant benefits in both surgical workflow and patient clinical outcome. The investigators hypotheses with regard to the del Nido solution will demonstrate (1) a non-inferior delivery to the current blood-based cardioplegia strategy in functional recovery or clinical outcome, and (2) superior delivery to the current blood-based cardioplegia strategy in cost analyses.

Detailed Description
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This prospective randomized controlled trial is designed for adult patients between the ages of 19-79 presenting for isolated CABG or single valve surgery, with or without CABG, requiring the use of Cardio-Pulmonary Bypass (CPB). Patients with previous cardiac surgery or requiring mechanical and pharmacologic support will be excluded from the study. Subjects randomized to the intervention group will receive del Nido cardioplegia solution during the aortic cross clamp period. The control group will receive whole-blood cardioplegia according to the Inova Fairfax Adult Cardioplegia protocol. Primary outcomes include clinical indicators for myocardial preservation such as serum troponin levels and the return of spontaneous rhythm. Surrogate primary endpoints for myocardial protection include the requirement for inotropic support and the need for defibrillation after coronary reperfusion. Secondary endpoints include post-operative clinical outcomes, duration of the aortic cross clamp period, and total expenses incurred during the patient length of stay. The investigators will conduct non-inferiority analyses to examine the effect of cardioplegia treatment arm on clinical outcomes and complications. Analyses of binary outcomes will use a 5% non-inferiority margin and analyses of continuous outcomes will use a 10% non-inferiority margin.

Official Title
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The Use of Del Nido Cardioplegia in Adult Cardiac Surgery: A Prospective Randomized Trial

Conditions
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Cardiac Perfusion

Intervention / Treatment
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* Other: del Nido solution
* Other: Blood-based cardioplegia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects able to receive and provide informed consent Elective surgical procedures requiring CPB and myocardial arrest Isolated coronary artery bypass graft (CABG) surgery or single valve surgery, with or without CABG Exclusion Criteria: Previous cardiac surgery Patients with preoperative inotropic pharmacological support Patients on preoperative mechanical circulatory support Patients with an implanted pacemaker or implantable cardioverter defibrillator Patients with non-isolated CABG or other non-CABG procedures with single valve surgery

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: del Nido solution<br>Administering of cardioplegia using del Nido solution in eligible patients. | Other: del Nido solution<br>* 1.0-liter of del Nido Cardioplegia after the aortic cross-clamp is applied to the ascending aorta. Delivery of del Nido solution will be administered in a 1:4 ratio of blood:crystalloid at a temperature of 6-10 degrees centigrade.<br>|
| Active Comparator: Blood-based cardioplegia<br>Administering of cardioplegia using current standard of care blood-based cardioplegia protocol. | Other: Blood-based cardioplegia<br>* An induction dose of whole blood cardioplegia ranging from 1.0-2.0 liters of solution will be given, with subsequent doses of cardioplegia every 20 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Return to spontaneous sinus rhythm | Return to spontaneous sinus rhythm measured as yes or no | Collected from beginning of surgery until transfer of patient out of the operating room. | 
| Defibrillation requirement | • Defibrillation requirement will be measured as: Defibrillation needed after coronary reperfusion (Y/N) Number of defibrillations required | Collected from beginning of surgery until discharge from the hospital, an expected average of 9 days. | 
| Hemodynamic instability | Measures as return to cardiopulmonary bypass (CPB) due to hemodynamic instability (Y/N) | Collected from beginning of surgery until discharge from the hospital, an expected average of 9 days. | 
| Change in blood troponin levels | • Blood troponin levels measured at: Baseline prior to surgery 2 hours after termination of cardiopulmonary bypass 12 hours after admission to the Cardiac Intensive Care Unit 24 hours after admission to the Cardiac Intensive Care Unit | Measured once immediately before surgery, then at 3 time-points post surgery (at 2, 12, 24 hours post-surgery). | 
| Inotropic requirement | • Inotropic requirements will be measures as: Inotropic pharmacologic support (Y/N) Duration of inotropic support after cardiopulmonary bypass measured in hours | Assessed from beginning of surgery until patient is discharged from the hospital, an expected average of 9 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-Operative Clinical Outcomes | Postoperative clinical outcomes, as defined by the Society of Thoracic Surgeons Adult Cardiac Surgical Database • Operative mortality and readmissions are assessed up to 30 days after surgery | Assessed from beginning of surgery until patient discharge from hospital, an expected average of 9 days, or up to 30 days after surgery for select outcomes (see below). | 
| Ejection fraction at termination of CPB | Calculated ejection fraction at termination of Cardiopulmonary bypass (via TEE- in percentage) | During surgical procedure at the termination of CPB | 
| Total duration of CPB | Cardiopulmonary bypass duration measured as the total number of minutes. | Measured during surgery from start to end of CPB | 
| Total aortic cross clamp duration | Aortic cross clamp duration measured as the total number of minutes. | Measured during surgery from start to end of aortic cross clamp | 
| Amount of cardioplegia solution | Total amount of cardioplegia solution administered measured in mL | Measured from start to end of surgery | 
| Cardioplegia costs | Cardioplegia costs (US dollars) including: Solution preparation Disposables Delivery system and associated tools | Measured from start to end of surgery | 
| Total expense of surgical stay | Total expenses incurred during entire patient length of hospital stay (US dollars) | Measured from patient admission to hospital until discharge from hospital, an expected average of 9 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CABG, valve surgery, cardioplegia, heart surgery, cardiac surgery, Cardio-Pulmonary Bypass, myocardial arrest, coronary artery bypass graft, CPB