A clinical trial comparing how well two solutions protect the heart during heart surgery in children

ISRCTN	ISRCTN13638147
DOI	https://doi.org/10.1186/ISRCTN13638147
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	2021-001915-10
Integrated Research Application System (IRAS)	279068
Protocol serial number	CPMS 49735, Grant Codes: CS/20/3/34738, IRAS 279068
Sponsor	University of Birmingham
Funder	British Heart Foundation

Submission date: 26/07/2021
Registration date: 28/07/2021
Last edited: 16/04/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
This study aims to improve the outcomes of children’s heart surgery so that they recover faster with fewer complications. Children with congenital heart defects often need operations to correct the abnormalities that they were born with. The surgery is complex and usually involves a period of support on a heart-lung machine (cardiopulmonary bypass). This allows the heart to be stopped for a short period of time, using a fluid called cardioplegia solution, whilst the defect is repaired. Inevitably, any surgery puts a strain on the heart and has the potential to cause damage. In this study, we will compare two types of cardioplegia solution used to stop the heart: del Nido, the most commonly used in children in the US, and St Thomas’, currently the standard practice in the UK, to determine which solution protects the heart better, and whether children recover faster and with fewer complications, so that we can improve the outcomes of children’s heart surgery.

Who can participate?
Children aged less than 16 years who are undergoing heart surgery requiring cardioplegia.

What does the study involve?
During the operation, the heart will need to be stopped for a period of time so that the surgeon can repair the heart defect. Being involved in this study will not affect whether the heart needs to be stopped during the operation – the only change will be the type of cardioplegia solution that is used. Both del Nido and St Thomas’ cardioplegia solutions are in routine clinical use in hospitals around the world and have been used in many thousands of children’s heart operations.

What are the possible benefits and risks of participating?
This trial will increase our understanding of which cardioplegia is better in children but there may not be any direct benefit for a child taking part. Whilst some previous studies have suggested that del Nido cardioplegia may better protect children’s hearts during surgery, we do not know if it is beneficial to all children and whether they recover faster with fewer complications - that is why we are conducting this study. We do not know whether being in the study will make your child’s surgery safer, but we are conducting it to understand how to improve the outcomes of children’s heart surgery in the future. Both types of cardioplegia are used routinely for heart surgery in children, del Nido in the US and St Thomas’ in the UK. The operation itself carries a risk, as discussed with the Surgeon and Cardiologist, but being involved in this study causes no additional pain, discomfort, distress or intrusion.

Where is the study run from?
This trial is being coordinated by the DESTINY trial office at Birmingham Clinical Trials Unit (BCTU) and is sponsored by the University of Birmingham (UK).

When is the study starting and how long is it expected to run for?
June 2021 to July 2025

Who is funding the study?
British Heart Foundation

Who is the main contact?
DESTINY trial office, DESTINY@trials.bham.ac.uk

Contact information

Mr Nigel Drury
Scientific

Department of Paediatric Cardiac Surgery
Birmingham Children’s Hospital
Steelhouse Lane
Birmingham
B4 6NH
United Kingdom

ORCID ID	0000-0001-9012-6683
Phone	+44 (0)121 3338731
Email	nigel.drury@nhs.net

Study information

Primary study design	Interventional
Study design	Interventional randomized controlled trial
Secondary study design	Randomised controlled trial
Participant information sheet	40206 DESTINY child info sheet v1.0 25Mar2021.pdf
Scientific title	del Nido versus St. Thomas’ blood cardioplegia in the young (DESTINY) trial: a multi-centre randomized controlled trial in children undergoing cardiac surgery
Study acronym	DESTINY
Study objectives	In children undergoing cardiac surgery, the use of del Nido cardioplegia, compared with St. Thomas’ blood cardioplegia, will reduce myocardial injury during surgery
Ethics approval(s)	Approved 30/06/2021, West Midlands - Coventry & Warwickshire Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; +44 (0)207 104 8009; coventryandwarwick.rec@hra.nhs.uk), ref: 21/WM/0149
Health condition(s) or problem(s) studied	Cardiac surgery
Intervention	The trial interventions are either del Nido cardioplegia (experimental arm) or St. Thomas’ blood cardioplegia (control arm). del Nido cardioplegia is administered in a 1:4 blood:crystalloid preparation, given at 4-8°C, with an initial dose of 20ml/kg and subsequent doses every 60-90 minutes if required, at the discretion of the surgeon, as required. St. Thomas’ blood cardioplegia is administered in a 4:1 blood:crystalloid using Harefield Hospital preparation, given at 4-8°C, with an initial dose of 20-30ml/kg, subsequent doses of 15 ml/kg every 20-30 minutes at the discretion of the surgeon, as required. Blood samples will be taken at several time-points: before the operation, once the child is asleep under anaesthesia; and at 5 timepoints after the operation, at 3, 6, 9, 12 and 24 hours after surgery. Following surgery, the child will be transferred to the Paediatric Intensive Care Unit and will be closely monitored. Follow-up in the trial will be until 30 days after the index operation.
Intervention type	Procedure/Surgery
Primary outcome measure(s)	Reduction in area under the time-concentration curve (AUC) for plasma high-sensitivity troponin-I (μg.h/L) in the first 24 hours after the index aortic cross-clamp release (reperfusion).
Key secondary outcome measure(s)	Current secondary outcome measures as of 14/03/2024: 1. Low cardiac output syndrome (LCOS) defined as either of the following: Vasoactive Inotrope Score (VIS) ≥15, or major cardiac event (cardiac arrest, ECLS or death) in the first 48 hours after reperfusion 2. Duration of mechanical ventilation (hours), defined as the number of hours from termination of index CPB to extubation 3. Length of postoperative stay on Paediatric Intensive Care (hours), defined as number of hours from admission to PICU from theatre following index procedure to discharge from PICU 4. Maximum VIS by thresholds: ≥10, ≥15 and ≥20 in the first 48 hours after reperfusion 5. Total VIS in the first 4 hours after PICU admission following the index procedure (score) 6. Arterial lactate (mmol/L) in the first 12 hours after reperfusion 7. Omega, determined by [SaO2]/[SaO2-ScvO2] in the first 12 hours after reperfusion 8. Total aortic cross-clamp time (mins) during the index procedure 9. Total volume of cardioplegia given (ml) during the index procedure 10. Need for internal defibrillation during reperfusion during the index procedure 11. Delayed sternal closure, incidence and duration (days) following the index procedure 12. Unplanned reoperation, including chest re-opening on PICU, following the index procedure 13. Need for new renal replacement therapy following the index procedure 14. Lowest estimated glomerular filtration rate (eGFR), calculated using the bedside Schwartz equation and the peak postoperative creatinine on routine monitoring during the first 7 days following the index procedure (ml/min/1.73m²), and according to the paediatric RIFLE categories 15. Length of postoperative stay in the hospital (days), defined as number of days from day of the index procedure to discharge from hospital or death, whichever is sooner 16. 30-day survival following the index procedure _____ Previous secondary outcome measures: 1. Low cardiac output syndrome (LCOS) defined as either of the following: Vasoactive Inotrope Score (VIS) ≥15, or major cardiac event (cardiac arrest, ECLS or death) in the first 48 hours after reperfusion 2. Duration of mechanical ventilation (hours), defined as the number of hours from termination of index CPB to extubation 3. Length of postoperative stay on Paediatric Intensive Care (hours), defined as number of hours from admission to PICU from theatre following index procedure to discharge from PICU 4. Maximum VIS by thresholds: ≥10, ≥15 and ≥20 in the first 48 hours after reperfusion 5. Total VIS in the first 4 hours after PICU admission following the index procedure (score) 6. Arterial lactate (mmol/L) In the first 12 hours after reperfusion 7. Omega, determined by [SaO2]/[SaO2-ScvO2] in the first 12 hours after reperfusion 8. Total aortic cross-clamp time (mins) during the index procedure 9. Total volume of cardioplegia given (ml) during the index procedure 10. Need for internal defibrillation during reperfusion during the index procedure 11. Delayed sternal closure, incidence and duration (days) following the index procedure 12. Unplanned reoperation, including chest re-opening on PICU, following the index procedure 13. Need for new renal replacement therapy following the index procedure 14. Lowest estimated glomerular filtration rate (eGFR), calculated using the bedside Schwartz equation and the peak postoperative creatinine on routine monitoring during the first 7 days following the index procedure (ml/min/1.73m2), and according to the paediatric RIFLE categories 15. Length of postoperative stay in the hospital (days), defined as number of days from day of the index procedure to discharge from hospital or death, whichever is sooner 16. 30-day survival following the index procedure
Completion date	31/07/2025

Eligibility

Participant type(s)	Patient
Age group	Child
Upper age limit	16 Years
Sex	All
Target sample size at registration	220
Total final enrolment	112
Key inclusion criteria	Children (<16 years) undergoing cardiac surgery on cardiopulmonary bypass with cardioplegic arrest
Key exclusion criteria	Current exclusion criteria as of 18/03/2025: 1. Predicted cross-clamp time <30 minutes (e.g. atrial septal defect, atrial septectomy, sub-aortic stenosis) at the discretion of the Consultant surgeon 2. Known contraindication to one of the constituents of either cardioplegia solution (e.g. lidocaine/procaine hypersensitivity/allergy) or its method of delivery, including temperature (e.g. haemoglobinopathy including sickle cell disease, cold agglutinins) 3. Ventricular assist device (VAD) insertion/explant or transplantation 4. Pre-operative inotropic support or extracorporeal life support (ECLS) 5. Previous cardiac surgery with cardioplegic arrest within the last 30 days 6. Previous enrolment in the DESTINY trial 7. Emergency surgery 8. Parent/guardian declines consent 9. Weight at the time of screening >50 kg _____ Previous exclusion criteria as of 14/03/2024: 1. Predicted cross-clamp time <30 minutes (e.g. atrial septal defect, atrial septectomy, sub-aortic stenosis) at the discretion of the Consultant surgeon 2. Known contraindication to one of the constituents of either cardioplegia solution (e.g. lidocaine/procaine hypersensitivity/allergy) or its method of delivery, including temperature (e.g. haemoglobinopathy including sickle cell disease, cold agglutinins) 3. Ventricular assist device (VAD) insertion/explant or transplantation 4. Pre-operative inotropic support or extracorporeal life support (ECLS) 5. Previous cardiac surgery with cardioplegic arrest within the last 30 days 6. Previous enrolment in the DESTINY trial 7. Emergency surgery 8. Parent/guardian declines consent 9. Weight at the time of surgery >50 kg _____ Previous exclusion criteria: 1. Predicted cross-clamp time <30 minutes (e.g. atrial septal defect, atrial septectomy, sub-aortic stenosis) at the discretion of the Consultant surgeon 2. Known contraindication to one of the constituents of either cardioplegia solution (e.g. lidocaine/procaine hypersensitivity/allergy) or its method of delivery, including temperature (e.g. haemoglobinopathy including sickle cell disease, cold agglutinins) 3. Ventricular assist device (VAD) insertion/explant or transplantation 4. Pre-operative inotropic support or extracorporeal life support (ECLS) 5. Previous cardiac surgery with cardioplegic arrest within the last 30 days 6. Emergency surgery 7. Parent/guardian declines consent (added 15/03/2023) 8. Weight at the time of surgery >50 kg 9. Previous enrolment in the DESTINY trial
Date of first enrolment	07/02/2022
Date of final enrolment	13/03/2025

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

Birmingham Children’s Hospital

Steelhouse Lane
Birmingham
B4 6NH
United Kingdom

Bristol Royal Hospital for Children

University Hospitals Bristol and Weston NHS Foundation Trust
Upper Mauldin Street
Bristol
BS2 8BJ
United Kingdom

Great Ormond Street Hospital

Great Ormond Street
London
WC1N 3JH
United Kingdom

Leeds General Infirmary (Children's Hospital)

The Leeds Teaching Hospitals NHS Trust
Great George Street
Leeds
LS1 3EX
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The current data sharing plans for this study are unknown and will be available at a later date.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article		14/04/2025	16/04/2025	Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Child version 1.0	25/03/2021	28/07/2021	No	Yes
Participant information sheet	Parent version 1.1a	06/07/2021	28/07/2021	No	Yes
Participant information sheet	Parent version 1.1b	06/07/2021	28/07/2021	No	Yes
Participant information sheet	Parent version 3.0a	05/10/2023	14/03/2024	No	Yes
Participant information sheet	Parent version 3.0b	05/10/2023	14/03/2024	No	Yes
Participant information sheet	Parent version 2.0a	27/08/2021	14/03/2024	No	Yes
Participant information sheet	Parent version 2.0b	27/08/2021	14/03/2024	No	Yes
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Protocol file	version 1.0	26/05/2021	28/07/2021	No	No
Protocol file	version 2.0	19/08/2021	14/03/2024	No	No
Protocol file	version 3.0	22/08/2022	14/03/2024	No	No
Protocol file	version 4.0	25/10/2023	14/03/2024	No	No
Protocol file	version 5.0	14/02/2025	18/03/2025	No	No
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Additional files

40206 DESTINY protocol v1.0 26May2021.pdf: Protocol file
40206 DESTINY child info sheet v1.0 25Mar2021.pdf: Child
40206 DESTINY parent info sheet v1.1a 06Jul2021.pdf: Parent
40206 DESTINY parent info sheet v1.1b 06Jul2021.pdf: Parent
ISRCTN13638147 DESTINY parent info sheet v3.0a 05Oct2023.pdf: Parent
ISRCTN13638147 DESTINY parent info sheet v3.0b 05Oct2023.pdf: Parent
ISRCTN13638147 DESTINY parent info sheet v2.0a 27Aug21.pdf: Parent
ISRCTN13638147 DESTINY parent info sheet v2.0b 27Aug21.pdf: Parent
ISRCTN13638147 DESTINY protocol v2.0 19Aug21.pdf: Protocol file
ISRCTN13638147 DESTINY protocol v3.0 22Aug22.pdf: Protocol file
ISRCTN13638147 DESTINY protocol v4.0 25Oct2023.pdf: Protocol file
ISRCTN13638147_PROTOCOL_V5.0_14Feb25.pdf: Protocol file

Editorial Notes

16/04/2025: Publication reference added.
18/03/2025: The following changes were made to the study record:
1. Protocol uploaded.
2. The recruitment end date was changed from 31/03/2025 to 13/03/2025.
3. Total final enrolment added.
4. Sponsor details and exclusion criteria updated.
28/08/2024: The overall end date was changed from 30/06/2025 to 31/07/2025.
27/08/2024: The following changes were made to the trial record:
1. The overall end date was changed from 25/07/2024 to 30/06/2025.
2. The recruitment end date was changed from 30/04/2024 to 31/03/2025.
3. The plain English summary was updated to reflect these changes.
14/03/2024: The following changes were made to the trial record:
1. The participant information sheets (2.0a, 2.0b, 3.0a, 3.0b) were uploaded as additional files.
2. The secondary outcome measures were changed.
3. The study website was added.
4. The exclusion criteria were changed.
5. The recruitment end date was changed from 31/05/2024 to 30/04/2024.
6. The intention to publish date was changed from 31/12/2024 to 31/12/2025.
7. Uploaded protocols v2.0, v3.0, v4.0 (not peer-reviewed) as additional files.
15/03/2023: The following changes were made to the trial record:
1. The overall start date was changed from 30/06/2021 to 26/07/2021.
2. The overall end date was changed from 31/12/2023 to 25/07/2024.
3. The recruitment start date was changed from 15/01/2022 to 07/02/2022.
4. The recruitment end date was changed from 14/07/2023 to 31/05/2024.
5. The exclusion criteria were changed.
6. The plain English summary was updated to reflect these changes.
29/12/2021: The following changes have been made:
1. The recruitment start date has been changed from 01/11/2021 to 15/01/2022.
2. The recruitment end date has been changed from 30/04/2023 to 14/07/2023.
21/09/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/03/2023 to 30/04/2023.
2. The recruitment start date was changed from 01/09/2021 to 01/11/2021.
28/07/2021: The protocol and participant information sheets were uploaded as additional files.
26/07/2021: Trial's existence confirmed by the NIHR.