Custodiol Versus Blood Cardioplegaia in Paediatric Cardiac Surgery

Congenital Heart Disease Clinical Trial

Official title:

Custodiol Versus Blood Cardioplegaia in Paediatric Cardiac Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03082716
• Other study ID #: IRB 2016-08 Custodiol Study
• Status: Completed
• Phase: Phase 2
• Start date: March 16, 2016
• Est. completion date: March 29, 2018

Study information

• Verified date: April 2023
• Source: King Faisal Specialist Hospital & Research Centre, Jeddah
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 .

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: March 29, 2018
• Est. primary completion date: March 29, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 18 Years

Eligibility

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 .

Related Conditions & MeSH terms

• Congenital Heart Disease
• Heart Defects, Congenital
• Heart Diseases

Intervention

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.
• 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.

Locations

Country	Name	City	State
Saudi Arabia	King Faisal Specialist Hospital and Research Centre	Jeddah	Western

Sponsors (1)

Lead Sponsor	Collaborator
King Faisal Specialist Hospital & Research Centre, Jeddah

Country where clinical trial is conducted

Saudi Arabia, 

References & Publications (8)

Bojan M, Peperstraete H, Lilot M, Tourneur L, Vouhe P, Pouard P. Cold histidine-tryptophan-ketoglutarate solution and repeated oxygenated warm blood cardioplegia in neonates with arterial switch operation. Ann Thorac Surg. 2013 Apr;95(4):1390-6. doi: 10.1 — View Citation

Chen Y, Liu J, Li S, Li W, Yan F, Sun P, Wang H, Long C. Which is the better option during neonatal cardiopulmonary bypass: HTK solution or cold blood cardioplegia? ASAIO J. 2013 Jan-Feb;59(1):69-74. doi: 10.1097/MAT.0b013e3182798524. — View Citation

Custodiol versus blood cardioplegia in pediatric cardiac surgery. SHAJ .October 2015 ;27,(4):327

elmorsy et al , Does type of cardioplegia affect myocardial and cerebral outcome in pediatric open cardiac surgeries? Ain-Shams Journal of Anesthesiology ,2014; 2(7) :242-249

Harvey B, Shann KG, Fitzgerald D, Mejak B, Likosky DS, Puis L, Baker RA, Groom RC; American Society of ExtraCorporeal Technology's International Consortium for Evidence-Based Perfusion and Pediatric Perfusion Committee. International pediatric perfusion practice: 2011 survey results. J Extra Corpor Technol. 2012 Dec;44(4):186-93. — View Citation

Korun O, Ozkan M, Terzi A, Askin G, Sezgin A, Aslamaci S. The comparison of the effects of Bretschneider's histidine-tryptophan-ketoglutarate and conventional crystalloid cardioplegia on pediatric myocardium at tissue level. Artif Organs. 2013 Jan;37(1):76-81. doi: 10.1111/j.1525-1594.2012.01575.x. — View Citation

Kotani Y, Tweddell J, Gruber P, Pizarro C, Austin EH 3rd, Woods RK, Gruenwald C, Caldarone CA. Current cardioplegia practice in pediatric cardiac surgery: a North American multiinstitutional survey. Ann Thorac Surg. 2013 Sep;96(3):923-9. doi: 10.1016/j.athoracsur.2013.05.052. Epub 2013 Jul 31. — View Citation

Liu J, Feng Z, Zhao J, Li B, Long C. The myocardial protection of HTK cardioplegic solution on the long-term ischemic period in pediatric heart surgery. ASAIO J. 2008 Sep-Oct;54(5):470-3. doi: 10.1097/MAT.0b013e318188b86c. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality (yes/no)	Death of all causes	up to 30 days
Primary	ICU stay (days)	length of ICU stay	up to 90 days (length of ICU stay required after the operative procedure recorded by days until discharge or death)
Primary	Arrhythmia (yes/no)	post operative arrythmia that required intervention	up to 48 hours
Secondary	length of stay (days)		up to 90 days (length of the hospital stay required since admission recorded by days until discharge or death )
Secondary	length of mechanical ventilation (hours)		up to 5 days
Secondary	myocardial biomarkers	(troponin and CKMB) measured (preoperatively,postoperatively 6h,24h,48h,)	up to 5 days
Secondary	Subjective ventricular function (normal,mildly depressed ,moderately depressed ,moderately-severe depressed ,severly depressed )	assessed by a cardiologist subjective assessment of the echocardiographically (preoperative ,immediate post repair ,24h post operative )	up to 24 hours
Secondary	Ejection fraction (percentage)	assessed by echocardiography (preoperative ,immediate post repair ,24h post operative )	up to 24 hours
Secondary	ECMO support (yes/no)		intraoperative
Secondary	vasoactive inotropic score ( low or high)	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