Del Nido Versus HTK Cardioplegia in Adult Aortic Valve Replacement

Comparison of Low Sodium Crystalloid Bretschneider-HTK Cardioplegia With Del Nido Cardioplegia in Patients Undergoing Elective Aortic Valve Replacement - a Prospective Randomized Trial

The goal of this clinical trial is to compare del Nido and Bretschneider-HTK (HTK) cardioplegia solutions in patients undergoing elective aortic valve replacement. The main question it aims to answer is:

• Does the del Nido cardioplegia provide better cardioprotection and clinical outcomes than HTK cardioplegia? Participants will receive one of the investigated cardioplegia solutions according to the randomization.

Researchers will compare both groups in terms of cardioprotection (described as levels of CK-MB and hsTnI), in-hospital clinical outcomes, biochemical changes in coronary sinus blood and one-year follow-up.

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Valve Disease; Valve Disease, Heart; Cardiac Ischemia
• Intervention / Treatment: Drug: Del Nido Cardioplegia Solution; Drug: HTK solution

Detailed Description

The idea of using del Nido cardioplegia in adult cardiac surgery appeared after many reports proving its safety and efficacy in the paediatric population. Therefore many adult centres started to apply it in everyday practice. Despite its growing popularity and application in different types of cardiac surgeries, there is still an insufficient number of prospective randomized trials which compare del Nido cardioplegia with the Bretschneider-HTK formula in the adult population.

The described problem will be analyzed at different levels in this prospective, randomised study.

Clinical aspects - del Nido and HTK cardioplegia will be compared in terms of intraoperative and postoperative details such as perfusion details and concentration of cardiac enzymes.

Echocardiographic changes - The next step will be revealing potential echocardiographic changes in cardiac function in short- and long-term observations after cardiac surgery.

Metabolic changes - the metabolic profile of amino acids and nucleotide changes after each cardioplegia solution delivery will be analyzed.

Statistical calculations will be performed by a qualified statistician. In the case of binary variables, Fisher's exact test will be used to assess differences between groups. In the case of quantitative variables, the compliance of the distribution with the normal distribution will be tested using the Shapiro-Wilk test. For quantitative variables with a distribution not significantly different from normal, the Student's t-test will be used for comparison between groups. If the distribution differs significantly from the normal distribution, the Mann-Whitney U test (comparisons of two samples) or the Kruskal-Wallis test (comparisons of many samples) will be used. Correlations between variables will be assessed using the Pearson or Spearman method, depending on the distribution of the variables. Repeated-measures ANOVA will be used to assess the variability of biochemical parameters over time.

In all analyses, p<0.05 will be considered as the level of statistical significance.

A comparison of the two cardioplegia solutions would allow assessing whether del Nido provides better cardioprotection than HTK.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Poland
  • Pomorskie
    • Gdańsk, Pomorskie, Poland, 80-282
      • Medical University of Gdansk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients aged 18 and over,
• qualified for elective isolated aortic valve replacement (AVR)

Exclusion Criteria:

• patients with significant coronary artery disease,
• urgent cases,
• cases with additional cardiac procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: del Nido cardioplegia group; A group of patients that received high potassium cardioplegic solution with the addition of lidocaine, mixed with the patient's blood in 4:1 ratio	Drug: Del Nido Cardioplegia Solution; The route of cardioplegia delivery differed according to surgeons' preferences. The total dosage of cardioplegia depends on the type of cardioplegia. The standard dose of del Nido cardioplegia in our institution is 1000 ml as an initial dose and is delivered with a system pressure of 90-150 mmHg. The solution is prepared by our hospital's pharmacy. At 60. minute of cross-clamp (XC) if XC time was expected to exceed 90 minutes another dose of solution would be delivered. The volume of an additional dose was 500 ml. The temperature of the delivered del Nido cardioplegia was 4*C.; Other Names: del Nido; DNC
Active Comparator: Bretschneider-HTK cardioplegia group; A group of patients that received low sodium cardioplegic solution with the addition of histidine, tryptophan and alpha-ketoglutarate	Drug: HTK solution; The route of cardioplegia delivery differed according to surgeons' preferences. The dose of the HTK cardioplegia is calculated with an application of 20 mL/kg rule. It is delivered with a system pressure of 90-150 mmHg. If the XC time exceeds 120 minutes additional dose is given (10 mL/kg rule). The temperature of the delivered crystalloid cardioplegia is 4*C; Other Names: HTK; Bretschneider-HTK

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative CK-MB	concentration of serum creatine kinase-myocardial band (CK-MB)	measured in the 6th, 24th, and 48th hour postoperatively
postoperative hsTnI	concentration of serum high sensitive cardiac troponin I (hsTnI)	measured in the 6th, 24th, and 48th hour postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CPB time	Time of cardiopulmonary bypass (CPB).	intraoperative
XC time	Time of aortic cross-clamp (XC).	intraoperative
Reperfusion time	Time of reperfusion (between removal of cross-clamp and weaning from cardiopulmonary bypass).	intraoperative
Cardioplegia volume	Total volume cardioplegia doses.	intraoperative
Cardioplegia doses	Number of cardioplegia doses.	intraoperative
Heart rhythm after XC	Type of heart rhythm after removal of aortic cross-clamp.	intraoperative
Need for defibrillation	Need for heart defibrillations in case of ventricular fibrillation.	intraoperative
Number of defibrillations	Number of heart defibrillations in case of ventricular fibrillation.	intraoperative
Intraoperative lactate concentration	Lactate measured before XC, at the time of the biggest hemodilution, and after CPB.	intraoperative
Intraoperative pH results	pH measured before XC, at the time of the biggest hemodilution, and after CPB.	intraoperative
Intraoperative partial pressure of oxygen	Partial pressure of oxygen measured before XC, at the time of the biggest hemodilution, and after CPB.	intraoperative
Intraoperative partial pressure of carbon dioxide	Partial pressure of carbon dioxide measured before XC, at the time of the biggest hemodilution, and after CPB.	intraoperative
Intraoperative base deficit	Base deficit measured before XC, at the time of the biggest hemodilution, and after CPB.	intraoperative
Intraoperative sodium and potassium concentration	Sodium and potassium concentration measured before XC, at the time of the biggest hemodilution, and after CPB.	intraoperative
Intraoperative amino acids concentrations	Changes of amino acid concentrations in systemic and coronary sinus blood Before the procedure - sample from the peripheral arterial line before the start of the procedure. During cardiopulmonary bypass - samples from the peripheral arterial line and samples from the coronary sinus at 1. and 5. minute after aortic cross-clamp removal. Blood from the coronary sinus would be collected by cannula for retrograde cardioplegia delivery. During reperfusion - peripheral arterial line blood sample would be collected after weaning from cardiopulmonary bypass.	intraoperative
Intraoperative nucleotides concentrations	changes of nucleotides concentrations in systemic and coronary sinus blood Before the procedure - sample from the peripheral arterial line before the start of the procedure. During cardiopulmonary bypass - samples from the peripheral arterial line and samples from the coronary sinus at 1. and 5. minute after aortic cross-clamp removal. Blood from the coronary sinus would be collected by cannula for retrograde cardioplegia delivery. During reperfusion - peripheral arterial line blood sample would be collected after weaning from cardiopulmonary bypass.	intraoperative
Ventilation time	Time of mechanical ventilation after surgery.	30 postoperative days
ICU length of stay	Intensive care unit (ICU) length of stay.	30 postoperative days
Hospital length of stay	Hospital length of stay.	30 postoperative days
Postoperative lactate concentration	Lactate measured at 6th, 24th, and 48th hour postoperatively.	30 postoperative days
Postoperative pH results	pH measured at 6th, 24th, and 48th hour postoperatively.	30 postoperative days
Postoperative partial pressure of oxygen	Partial pressure of oxygen measured at 6th, 24th, and 48th hour postoperatively.	30 postoperative days
Postoperative partial pressure of carbon dioxide	Partial pressure of carbon dioxide measured at 6th, 24th, and 48th hour postoperatively.	30 postoperative days
Postoperative base deficit	Base deficit measured at 6th, 24th, and 48th hour postoperatively.	30 postoperative days
Postoperative sodium and potassium levels	Sodium and potassium levels measured at 6th, 24th, and 48th hour postoperatively.	30 postoperative days
Maximum CRP concentration	Maximum C reactive protein (CRP) concentration measured during hospitalization at our institution.	30 postoperative days
Discharge CRP concentration	CRP results at discharge from our institution.	30 postoperative days
Maximum creatinine concentration	Maximum creatinine concentration measured during hospitalization at our institution.	30 postoperative days
Discharge creatinine concentration	Creatinine results at discharge from our institution.	30 postoperative days
Discharge Hb concentration	Hemoglobin (Hb) results at discharge from our institution.	30 postoperative days
Discharge Hct concentration	Hematocrit (Hct) results at discharge from our institution.	30 postoperative days
Discharge WBC concentration	White blood cells count (WBC) results at discharge from our institution.	30 postoperative days
VIS	Vasoactive-inotropic score (VIS) at 6th, 24th, and 48th hour postoperatively.	30 postoperative days
Rate of postoperative transfusions	Rate of postoperative blood product transfusions.	30 postoperative days
Rate of resternotomy	Rate of bleeding with the need for re-sternotomy during the early postoperative period.	30 postoperative days
Rate of pericardial drainage	Rate of pericardial drainages during the early postoperative period.	30 postoperative days
Rate of stroke	Rate of stokes during the early postoperative period.	30 postoperative days
Rate of myocardial infarction	Rate of myocardial infarction during the early postoperative period.	30 postoperative days
Rate of new-onset arrhythmias	Rate of new-onset arrhythmias (atrial fibrillation, heart block) during the early postoperative period.	30 postoperative days
In-hospital mortality rate	Rate of postoperative deaths that occurred during initial hospitalization.	30 postoperative days
Out-hospital mortality rate	Rate of postoperative deaths that occurred after hospital discharge.	approx one year postoperatively
Rate of pacemaker implantation	Pacemaker implantation in postoperative period.	approx one year postoperatively
Rate of secondary hospitalization	Rate of secondary hospitalization due to late complications or other cardiac-related reasons	approx one year postoperatively
LVEF values changes	Left ventricular ejection fraction (LVEF) will be measured during an echocardiography test before surgery, before discharge and one year after surgery.	approx one year postoperatively
Diastolic function changes	Diastolic function measured during an echocardiography test before surgery, before discharge and one year after surgery.	approx one year postoperatively
2STE parameter changes	2STE parameter changes (with special attention put on the ventricular septum, new hypokinetic or akinetic areas) measured during an echocardiography test before surgery, before discharge and one year after surgery.	approx one year postoperatively

Collaborators and Investigators

• Sponsor: Medical University of Gdansk
• Investigators: Principal Investigator: Barbara Brzeska, MD, Medical Univeristy of Gdansk

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): April 24, 2023
• Study Completion (Estimated): September 24, 2024

Study Registration Dates

• First Submitted: December 5, 2023
• First Submitted That Met QC Criteria: January 21, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 21, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: cardiac surgery; aortic valve replacement; cardioprotection; del Nido cardioplegia; Bretschneider HTK cardioplegia
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Ischemia; Heart Valve Diseases; Aortic Valve Disease; Pharmaceutical Solutions; Cardioplegic Solutions; Del Nido cardioplegia solution
• Other Study ID Numbers: NKBBN/203/2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data obtained through this study may be provided to qualified researchers with an interest in cardioprotection. Data or samples shared will be coded, with no PHI included.

The data underlying this article will be shared on reasonable request.

• IPD Sharing Time Frame: was not yet determined
• IPD Sharing Access Criteria: The data underlying this article will be shared on reasonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No