Protecting the heart with remote ischaemic preconditioning during children's heart surgery
| ISRCTN | ISRCTN12923441 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12923441 |
| IRAS number | 200876 |
| Secondary identifying numbers | 1845, IRAS 200876 |
- Submission date
- 30/04/2016
- Registration date
- 25/05/2016
- Last edited
- 05/04/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Congenital heart disease is a general term used to describe a range of birth defects that affect the way the heart works. Children with congenital heart disease often need operations to correct the abnormality that they were born with to improve their chance of survival and quality of life. The surgery is complex and usually involves a period of support on a heart-lung machine (cardiopulmonary bypass) whilst the defect is repaired. The surgery puts a strain on the child’s heart and may potentially cause a type of damage called ischaemia-reperfusion injury (tissue damage when the blood supply to the heart is interrupted and restored). Previous studies have found that using a blood pressure cuff to stop blood flow to one or more limbs (Remote ischemic preconditioning (RIPC)) for short periods immediately before surgery may reduce any damage to the heart during surgery and thereby make the surgery safer. This study is going to look at RIPC in children with two common types of congenital heart conditions, ventricular septal defect (in which there is a hole in the wall between the lower chambers of the heart) and tetralogy of Fallot (a condition which combines four defects in the heart muscle). The aim of this study is to find out whether RIPC improves heart protection in all or just some children.
Who can participate?
Children aged between three months and three years who are undergoing surgery due to a heart defect they were born with (Tetralogy of Fallot or Ventricular Septal Defect).
What does the study involve?
Children are randomly allocated to one of two groups. Those in the first group receive RIPC. This involves placing a tourniquet (precisely controlled blood pressure cuff) around the top of each leg once the child is asleep (under anaesthesia) and inflating it for 5 minutes to stop the blood supply, then deflating it for 5 minutes to allow the blood supply to resume. This is repeated three times to get the most accurate result. For those in the second group, the cuffs are placed beside the patient around a dummy limb for the inflation-deflation cycles. In all cases, the cuffs are covered with a drape to ensure that it is not known which procedure the children receive. For both groups, blood and muscle samples are taken during surgery to measure if there is a difference in how the heart cells make energy between children with normal or low blood oxygen levels and whether this is affected by using RIPC.
What are the possible benefits and risks of participating?
There may not be any benefit from participating as whilst some previous studies have shown that the blood pressure cuff technique helps to protect children’s hearts from injury during surgery, it is unknown whether it is beneficial to all children with all types of congenital heart disease. There are no notable risks of participating, as the technique being used is safe with no complications reported related to the technique in either children or adults undergoing any type of surgery.
Where is the study run from?
University of Birmingham (UK), Birmingham Children's Hospital (UK), and Leeds Children's Hospital (UK)
When is the study starting and how long is it expected to run for?
December 2014 to December 2020
Who is funding the study?
British Heart Foundation (UK)
Who is the main contact?
Mr Nigel Drury
nigel.drury@nhs.net
Contact information
Public, Principal Investigator
Department of Cardiac Surgery
Birmingham Children's Hospital
Steelhouse Lane
Birmingham
B4 6NH
United Kingdom
 ORCID ID |
0000-0001-9012-6683 |
|---|---|
| Phone | +44 121 333 9435 |
| nigel.drury@nhs.net |
Study information
| Study design | Two-centre prospective double-blind randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | The Bilateral Remote Ischaemic Conditioning in Children trial |
| Study acronym | BRICC |
| Study objectives | 1. Remote ischemic preconditioning (RIPC) improves myocardial protection and reduces markers of IR injury in young children undergoing surgery; however, the benefits may be attenuated in those with chronic hypoxia 2. RIPC leads to a reduction in the accumulation of citric acid cycle intermediates during ischaemia; however, this effect may be reduced in those with chronic hypoxia 3. Succinate concentration is significantly higher in the chronically hypoxic myocardium than in the previously normoxic heart, both at the onset and at the end of surgical ischaemia |
| Ethics approval(s) | Approved 05/08/2016, West Midlands-Solihull NHS Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS; +44 0207 104 8019; NRESCommittee.WestMidlands-Solihull@nhs.net), ref: 16/WM/0309 |
| Health condition(s) or problem(s) studied | Prevention of ischaemia-reperfusion injury in children undergoing surgery for tetralogy of Fallot or ventricular septal defect |
| Intervention | On the day of surgery, participants will be randomised to either Remote Ischaemic Preconditioning (RIPC) or control in a 1:1 ratio using an online randomisation system. Patients will be stratified for the congenital heart defect undergoing repair (TOF or VSD) and the presence of a RVOT stent in patients with TOF. In all cases, the cuffs will be covered with a drape to maintain blinding. RIPC group: After induction of anaesthesia but prior to sternotomy, participants will receive RIPC induced by 3 cycles of 5-minutes ischaemia and 5-minutes reperfusion. Ischaemia will be induced simultaneously in two limbs using the PTSii system (Delfi Medical, Vancouver), a state-of-the-art digital tourniquet with precise control of occlusion pressure. Age-appropriate PediFit cuffs, with Contour limb protection sleeves, will be placed around both thighs and inflated to at least 50mmHg above systolic pressure measured via the arterial line; if vascular access is problematic and the femoral route is required by the anaesthetist, one cuff will be placed on the thigh and the other on the upper arm. Control group: The cuffs will be placed beside the patient for sham inflation-deflation cycles on a dummy limb. Following surgery, all patients will be followed-up until discharge from hospital or 30 days, whichever is sooner. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | Myocardial injury, determined by area under the time-concentration curve (AUC) for high-sensitivity troponin-T in the first 24 hours, measured at baseline, 3, 6, 12 and 24 hours after aortic cross-clamp release (reperfusion). |
| Secondary outcome measures | Current secondary outcome measures as of 24/03/2020: 1. Myocardial injury, measured by peak hs-troponin-T in the first 12 hours, measured at baseline, 3, 6 and 12 hours after reperfusion 2. Inotropic support, determined by vasoactive inotrope score over the first 12 hours after reperfusion 3. Metabolic debt, measured by serum lactate concentration and mixed venous oxygen saturations over the first 12 hours after reperfusion 4. Length of stay, determined by the period of time required in the paediatric intensive care unit and the hospital following surgery 5. Exploratory outcome: myocardial function, measured by cardiac index using the ICON device over the first 12 hours after reperfusion Previous secondary outcome measures: 1. Myocardial injury, measured by peak hs-troponin-T in the first 12 hours, measured at baseline, 3, 6, 12 and 24 hours after reperfusion 2. Myocardial function, measured by cardiac index using the ICON device over the first 12 hours after reperfusion 3. Inotropic support, determined by inotrope score over the first 12 hours after reperfusion 4. Metabolic debt, measured by serum lactate concentration and mixed venous oxygen saturations over the first 12 hours after reperfusion 5. Length of stay, determined by the period of time required in the paediatric intensive care unit and the hospital following surgery |
| Overall study start date | 11/12/2014 |
| Completion date | 21/12/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 3 Months |
| Upper age limit | 3 Years |
| Sex | Both |
| Target number of participants | 120 |
| Total final enrolment | 120 |
| Key inclusion criteria | Current participant inclusion criteria as of 24/03/2020: 1. Aged 3 months to 3 years at the time of surgery 2. Undergoing elective primary repair of Tetralogy of Fallot (TOF) or Ventricular Septal Defect (VSD), with or without a concomitant atrial septal defect (ASD) or pulmonary artery repair/augmentation, at Birmingham Children’s Hospital or Leeds Children’s Hospital. Previous participant inclusion criteria: 1. Aged 3 months to 3 years at the time of surgery 2. Undergoing elective primary repair of Tetralogy of Fallot (TOF) or Ventricular Septal Defect (VSD), with or without a concomitant atrial septal defect (ASD) |
| Key exclusion criteria | Current participant exclusion criteria as of 24/03/2020: 1. Those requiring an additional procedure (other than ASD closure) at the time of primary repair e.g. aortic arch repair 2. Those with significant airway or parenchymal lung disease, bleeding disorder or recent ischaemic event 3. Those who have undergone a previous cardiac surgical procedure with cardioplegic arrest. 4. Those presenting in a critical condition and requiring emergency cardiac surgery 5. Those for whom the parents are unwilling or unable to give informed consent Previous participant exclusion criteria: 1. Those requiring an additional procedure (other than ASD closure) at the time of primary repair e.g. aortic arch repair 2. Those with a known major chromosomal defect, significant airway or parenchymal lung disease, bleeding disorder or recent ischaemic event 3. Those presenting in a critical condition and requiring emergency cardiac surgery 4. Those for whom the parents are unable to give informed consent |
| Date of first enrolment | 15/08/2016 |
| Date of final enrolment | 08/12/2020 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Birmingham
B4 6NH
United Kingdom
Leeds General Hospital
Leeds
LS1 3EX
United Kingdom
Sponsor information
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Website | https://intranet.birmingham.ac.uk/finance/accounting/Research-Support-Group/Research-Governance/index.aspx |
|---|---|
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- the_bhf, The British Heart Foundation, BHF
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 04/03/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The findings of this clinical trial and metabolomics studies will be submitted for presentation at national and international meetings. Manuscripts will be prepared for submission to leading journals. |
| IPD sharing plan | Requests for access to data should be addressed to the Chief Investigator Nigel Drury (nigel.drury@nhs.net). Individual participant data collected during the trial (including the data dictionary) will be available, after deidentification, when the article has been published with no end date. All proposals requesting data access must specify how the data will be used, and all proposals will need the approval of the Trial Management Committee before data release. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 07/10/2020 | 14/10/2020 | Yes | No |
| Other publications | Qualitative substudy results | 23/02/2021 | 25/02/2021 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 05/03/2024 | 05/04/2024 | Yes | No |
Editorial Notes
05/04/2024: The following changes were made to the study record:
1. Publication reference and IPD sharing statement added.
2. The intention to publish date was changed from 31/12/2023 to 04/03/2024.
03/10/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/10/2020 to 08/12/2020.
2. The overall end date was changed from 31/10/2020 to 21/12/2020.
3. The intention to publish date was changed from 01/03/2021 to 31/12/2023.
4. The plain English summary was updated to reflect these changes.
5. The target number of participants was changed from 104 to 120.
6. The total final enrolment was added.
25/02/2021: Publication reference added.
14/10/2020: Publication reference added.
23/03/2020: The following changes have been made:
1. The recruitment end date has been changed from 31/03/2019 to 31/10/2020.
2. The overall trial end date has been changed from 31/03/2019 to 31/10/2020.
3. The intention to publish date has been changed from 31/12/2019 to 01/03/2021.
4. The scientific title has been changed from "The Birmingham Remote Ischaemic Conditioning in Children trial" to "The Bilateral Remote Ischaemic Conditioning in Children trial".
5. The ethics approval has been added.
6. The scientific contact has been updated.
7. The trial participating centre "Leeds Children's Hospital" has been added.
8. The secondary outcome measures have been updated.
9. The participant inclusion criteria have been updated.
10. The participant exclusion criteria have been updated.
11. The study design has been changed from "Single-centre prospective double-blind randomised controlled trial" to "Two-centre prospective double-blind randomised controlled trial".
12. The IRAS number has been added.
13. The plain English summary has been updated to reflect the changes above.
13/03/2020: Internal review.
