Study of Organ Perfusion in Heart Transplantation in Children

Study Overview
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Brief Summary
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The goal of this prospective randomized single blind multicenter phase II study is to compare organ perfusion with Custodiol-N and Custodiol in heart transplantation in children of all ages (birth to <18 years) being listed on the waiting list for heart transplantation. The main question it aims to answer is: to compare the safety of Custodiol-N in heart transplantation in children in comparison to its precursor product Custodiol. Participants will receive either a heart to be transplanted, either perfused with Custodiol-N or Custodiol to Researchers will compare the two solutions to see if the new solution Custodiol-N is safe in heart transplantation in children.

Detailed Description
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Orthotopic Heart transplantation (or cardiac transplantation) is a procedure performed in patients with end stage heart failure when other treatments have failed. The surgical procedures for orthotopic heart transplantation are essentially the same in adult and paediatric patients . Due to anatomical variants in congenital heart disease the procurement procedure may be modified with regard to the extent of the Vena cava superior and the great vessels. In implantation most frequently the bicaval technique is used but the biatrial technique which is leaving the back wall of both atria in situ may also be employed. A main difference between adult and paediatric heart transplantation (HTx) are the indications for transplantation: In adults the majority of patients undergo HTx as treatment of end stage heart failure due to cardiomyopathy or severe coronary artery disease when other treatments have failed. Infants younger than one year of age congenital heart disease (CHD) is the most common diagnosis representing more than every second case followed by dilated cardiomyopathy (DCM) in more than one third of cases. In older patients DCM is the most frequent underlying diagnosis. CHD may include patients who have undergone corrective surgery and in whom myocardial dysfunction develops later .

Official Title
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A Prospective Randomized Single Blind Multicenter Phase II Study of Organ Perfusion With Custodiol-N Compared With Custodiol in Heart Transplantation in Children

Conditions
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Heart Transplantation

Intervention / Treatment
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* Drug: Custodiol-N
* Drug: Custodiol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from birth to less than18 years Recipients awaiting their first transplant Ability of the patients and/ or their legal guardians to understand character and individual consequences of the clinical trial written informed consent of the patients and/ or their legal guardians (must be available before enrolment in the study) Patient listed on the waiting list for heart transplantation Exclusion Criteria: Patients who have participated within 30 days or are still participating in any other interventional studies history of severe organic disease other than concerning the heart history/demonstration of HIV antibodies or AIDS multiorgan transplantation machine-perfused organ the explantation team is affiliated to another clinic than transplantation team Failing Fontan patients Patients who have been incarcerated or involuntarily institutionalized by court order or by the authorities Pregnancy and lactation

Ages Eligible for Study
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Minimum Age: 24 Hours
Maximum Age: 17 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Custodiol-N<br>organ will be perfused with Custodiol-N solution | Drug: Custodiol-N<br>* heart will preserved in and will be treated with Custodiol-N solution<br>* Other names: Solution for organ preservation in transplantation;|
| Active Comparator: Custodiol<br>organ will be perfused with Custodiol solution | Drug: Custodiol<br>* heart will preserved in and will be treated with Custodiol solution<br>* Other names: Solution for organ preservation in transplantation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse event reporting | Safety assessment | up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| heart rate | vital parameters | up to day 7 after release of the aortic cross clamp | 
| blood pressure (systolic (SBP) and diastolic (DBP)) | vital parameters | up to day 7 after release of the aortic cross clamp | 
| body temperature | vital parameters | up to day 7 after release of the aortic cross clamp | 
| concentration of cardiac troponin | laboratory tests | up to day 7 after release of the aortic cross clamp | 
| concentration of creatinine kinase (CK-MB) | laboratory tests | up to day 7 after release of the aortic cross clamp | 
| (SBP (systolic blood pressure), DBP (diastolic blood pressure)) | Haemodynamics | from termination of cardiopulmonary bypass until transfer to intensive care unit | 
| Heart Rhythm (HR) | Haemodynamics | from termination of cardiopulmonary bypass until transfer to intensive care unit | 
| Pulmonary artery pressure (PAP (if available)) | Haemodynamics | from termination of cardiopulmonary bypass until transfer to intensive care unit | 
| Cerebrovascular resistance (CVR (if available)) | Haemodynamics | from termination of cardiopulmonary bypass until transfer to intensive care unit | 
| Death | survival | up to 12 months | 
| function of transplanted organ (heart) | Graft survival | up to 3 months | 
| Readmission to intensive care unit (ICU) | return to intensive care unit | up to 3 months | 
| Length of ICU stays | duration of stay in intensive care unit | up to 3 months | 
| Catecholamine requirement | (yes/no) | up to day 7 | 
| Antihypertensives intake | (yes/no) | up to 12 months | 
| Milrinone support | (yes/no) | up to day 7 | 
| Need for pacemaker therapy | (yes/no) | up to day 7 | 
| Left and right ventricular assist device (LVAD, RVAD) | Device therapy (each yes/no) | up to 3 months | 
| Extracorporeal membrane oxygenation (ECMO) | Device therapy (each yes/no) | up to 3 months | 
| Biventricular assist Device (BIVAD) or percutaneous LVAD | Device therapy (each yes/no) | up to 3 months | 
| Ejection fraction | Echocardiographic markers of function and rejection | up to day 7 | 
| enddiastolic and endsystolic ventricle | Echocardiographic markers of function and rejection | up to day 7 | 
| Cardiac arrhythmias | occurrence, severity, type | up to day 7 |