Del Nido Cardioplegia Randomized Trial

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

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.

Study Overview

• Status: Terminated
• Conditions: Cardiac Perfusion
• Intervention / Treatment: Other: del Nido solution; Other: Blood-based cardioplegia

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Heart and Vascular Institute
    • Falls Church, Virginia, United States, 22042
      • CVTSA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: del Nido solution; Administering of cardioplegia using del Nido solution in eligible patients.	Other: del Nido solution; 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.
Active Comparator: Blood-based cardioplegia; Administering of cardioplegia using current standard of care blood-based cardioplegia protocol.	Other: Blood-based cardioplegia; 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.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Inova Health Care Services

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): April 4, 2017
• Study Completion (Actual): April 4, 2017

Study Registration Dates

• First Submitted: March 30, 2015
• First Submitted That Met QC Criteria: May 8, 2015
• First Posted (Estimate): May 13, 2015

Study Record Updates

• Last Update Posted (Actual): January 12, 2022
• Last Update Submitted That Met QC Criteria: December 23, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: cardiac surgery; CABG; coronary artery bypass graft; CPB; heart surgery; valve surgery; cardioplegia; Cardio-Pulmonary Bypass; myocardial arrest
• Other Study ID Numbers: #14-1653