Custodiol Versus Blood Cardioplegaia in Paediatric Cardiac Surgery

April 12, 2023 updated by: King Faisal Specialist Hospital & Research Centre, Jeddah
Cardioplegic arrest is an essential part of cardiac surgery which aims to allow myocardial preservation and minimise myocardial swelling ,while providing a motionless and bloodless field ,.Blood cardioplegia has proven its efficacy for several decades and surgeons are still preferring to use it for myocardial protection of paediatric cardiac surgery ,although it is thought to be more time consuming since it is given with interrupted doses, . Even when advancement has came along the field of myocardial protection and cardioplegia solutions with the introduction of Bretschneider Histidine-Tryptophan-Ketoglutarate solution ,custodiol ,in 1970 ,which is given as a single dose and believed to be convenient, simple to deliver , and less time consuming . Many Surgeons haven't change their practice possibly due to paucity of studies comparing cardioplegia solutions in paediatric cardiac surgery and conflicting reports regarding the superiority of different cardioplegia solution.The investigators aim to provide evidence that will help paediatric cardiac surgeons to choose the optimal solution for their practice .

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hypothesis :

Custodial is not inferior to blood cardioplegia in myocardial protection in paediatric cardiac surgery ..

Methodology :

Study design :

Randomized controlled trial

Data collection:

All demographic data ,diagnosis ,procedure(type.CPB time ,crossclamp time) , surgeon and hospital course details .

Computer generated randomisation into two groups based on cardioplegia solution .

if randomised to blood patient will receive blood cardioplegia, delivered by microplegia delivery system by adding potassium to the blood (K= 35 ml eq/L) . The initial dose will be 35ml/ kg, and subsequent doses 20-15 ml/kg given every 20 minutes at a Temperature of 10 - 15 °C, while maintaining a perfusion pressure of 100-125 mmHg.

if randomised to custodial patient will receive single dose of HTK custodiol cardioplegia. at temperature of 4-8°C and will be perfused for 6-8 minutes. Dose will start from 400 up to 1000 ml according to the child's body weight. Perfusion pressure will be kept at 70 - 80 mmHg until the heart is arrested..

Blinding :

Surgeons will know the type of cardioplegia in the OR while other assessor will be blinded .

Sample size calculated with an online calculator based on α error of 0.05 and β error of 0.2 to detect an absolute risk difference of 15% in composite end point between the two groups yielded 137 in each arm ,The results will be presented as mean (SD), median (interquartile range), or proportion . Using relative risk and log rank for statistical analysis .A P value of less than 0.05 will be considered statistically significant. Statistical analyses will be carried out using the SPSS .

Safety monitoring and interim results :

Both cardioplegia solutions are already in use and FDA approved there is no safety concerns at the time being . However , an interim analysis will be carried on every 6 months and the principal investigator will decide weather to stop or carry on if any major discrepancies in outcomes

literature review : After an extensive literature review the investigators found only one randomised trial by elmorsy et al , which concluded that A single dose of an HTK cardioplegic solution provides better myocardial and cerebral protection than repeated doses of oxygenated blood cardioplegia during pediatric congenital cardiac surgery.

On the other hand there was another retrospective report by bojan et al, found that The use of Custodiol cardioplegia in neonates undergoing ASO was associated with a larger troponin release when compared with warm blood cardioplegia,p <0.001 suggesting poor myocardial protection.

koruon et al, done a tissue level comparison between htk and conventional crystalloid cardioplegia and their statistical analysis revealed no significant difference between the two groups regarding the clinical variables, apoptotic indices and proliferation indices.

Liu j et al ,did a retrospective study comparing custodiol to St. Thomas crystalloid cardioplegia which concluded That HTK group had shorter cross-clamping time and more frequent spontaneous defibrillation than St. Thomas group.

Also an animal study by Chen Y et al, on piglets that were randomised to either a single dose of HTK or multidose cold blood cardioplegia .. No significant differences were noted in the myocardial lactate content, ATP content, and histopathological score between both groups .

Finally a retrospective report by E Qulisy et al concluded that Custodiol cardioplegia is associated with less myocardial protection and higher adverse outcomes compared to blood cardioplegia in pediatric age group undergoing cardiac surgery.

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Saudi Arabia
    • Western
      • Jeddah, Western, Saudi Arabia, 40047
        • King Faisal Specialist Hospital and Research Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • All paediatric patients referred to our hospital which will undergo open cardiac repair with cardiopulmonary bypass and cardioplegic arrest .

Exclusion Criteria:

  • All emergency procedure( require immediate surgery)
  • Cases that don't require use of cardioplegia .

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: blood cardioplegia group
patient will receive blood cardioplegia, delivered by microplegia delivery system by adding potassium to the blood (K= 35 ml eq/L) . The initial dose will be 35ml/ kg, and subsequent doses 20-15 ml/kg given every 20 minutes at a Temperature of 10 - 15 °C, while maintaining a perfusion pressure of 100-125 mmHg.
Drug: Blood cardioplegia
After cross clamping patient will receive blood cardioplegia, delivered by microplegia delivery system by adding potassium to the blood (K= 35 ml eq/L) . The initial dose will be 35ml/ kg, and subsequent doses 20-15 ml/kg given every 20 minutes at a Temperature of 10 - 15 °C, while maintaining a perfusion pressure of 100-125 mmHg.
Experimental: custodiol group
patient will receive single dose of HTK custodiol cardioplegia. at temperature of 4-8°C and will be perfused for 6-8 minutes. Dose will start from 400 up to 1000 ml according to the child's body weight. Perfusion pressure will be kept at 70 - 80 mmHg until the heart is arrested.
Drug: Custodiol Solution
After cross clamping patient will receive single dose of HTK custodiol cardioplegia. at temperature of 4-8°C and will be perfused for 6-8 minutes. Dose will start from 400 up to 1000 ml according to the child's body weight. Perfusion pressure will be kept at 70 - 80 mmHg until the heart is arrested.
Other Names:
  • htk

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality (yes/no)
Time Frame: up to 30 days
Death of all causes
up to 30 days
ICU stay (days)
Time Frame: up to 90 days (length of ICU stay required after the operative procedure recorded by days until discharge or death)
length of ICU stay
up to 90 days (length of ICU stay required after the operative procedure recorded by days until discharge or death)
Arrhythmia (yes/no)
Time Frame: up to 48 hours
post operative arrythmia that required intervention
up to 48 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
length of stay (days)
Time Frame: up to 90 days (length of the hospital stay required since admission recorded by days until discharge or death )
up to 90 days (length of the hospital stay required since admission recorded by days until discharge or death )
length of mechanical ventilation (hours)
Time Frame: up to 5 days
up to 5 days
myocardial biomarkers
Time Frame: up to 5 days
(troponin and CKMB) measured (preoperatively,postoperatively 6h,24h,48h,)
up to 5 days
Subjective ventricular function (normal,mildly depressed ,moderately depressed ,moderately-severe depressed ,severly depressed )
Time Frame: up to 24 hours
assessed by a cardiologist subjective assessment of the echocardiographically (preoperative ,immediate post repair ,24h post operative )
up to 24 hours
Ejection fraction (percentage)
Time Frame: up to 24 hours
assessed by echocardiography (preoperative ,immediate post repair ,24h post operative )
up to 24 hours
ECMO support (yes/no)
Time Frame: intraoperative
intraoperative
vasoactive inotropic score ( low or high)
Time Frame: up to 48 hour

Vasoactive Inotropic score : (all doses of inotropes recorded hourly during 48 h)

Dopamine dose (μg/kg/min) + Dobutamine dose (μg/kg/min) +100 × epinephrine dose (μg/kg/min)+ 10 X Milrinone dose (μg/kg/min) +10,000 × Vasopressin dose (U/kg/min) + 100 × Norepinephrine dose (μg/kg/min)

calculated hourly for 48 hours and added than divided by 48 to give the score . if maximum score < 20 its low VIS and if maximum score ≥ 20 its a high VIS
up to 48 hour

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

King Faisal Specialist Hospital & Research Centre, Jeddah

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 16, 2016

Primary Completion (Actual)

March 29, 2018

Study Completion (Actual)

March 29, 2018

Study Registration Dates

First Submitted

January 29, 2017

First Submitted That Met QC Criteria

March 12, 2017

First Posted (Actual)

March 17, 2017

Study Record Updates

Last Update Posted (Estimate)

April 13, 2023

Last Update Submitted That Met QC Criteria

April 12, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB 2016-08 Custodiol Study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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