Ischaemic Reperfusion Injury Clinical Trial
Official title:
Effect of Remote Ischaemic Preconditioning in Cardiac Dysfunction and End-organ Injury Following Cardiac Surgery With Cardiopulmonary Bypass in Children.
Surgical correction of congenital heart defects in children requires the utilization of
cardiopulmonary bypass, a technique that temporarily substitutes heart and lung functions
during surgery. During this process the patient´s circulation is controlled by a bypass
machine which provides several functions:
1. Controls the patient's blood flow by pumping of blood in the patient's body.
2. Controls the correct oxygen levels in the patient's blood.
3. Regulates the temperature and fluid level of the blood. This process triggers negative
responses in the heart and throughout the whole body, potentially resulting in injury
to the heart and other organs such as brain, kidneys and lungs.
Remote ischaemic preconditioning (RIPC) describes a procedure that could potentially reduce
the injury to heart muscle during cardiac surgery. The procedure consists of the inflation
of a blood pressure cuff on the child's leg for three 5 minute cycles. This process acts by
briefly reducing blood flow to the leg muscle, which will then activate the body´s own
protective mechanisms and thereby reduce heart injury.
Several animal studies have been used to help the understanding of the mechanisms behind
this process, and trials in human adults have showed optimistic results; however evidence
regarding the paediatric population is limited and necessary since children present
different basal profiles, risks and requirements.
The investigators propose a randomized clinical trial assessing the efficacy of RIPC to
provide protection against injury to the heart and other organs in children going through
cardiac surgery using CPB at the Royal Hospital for Sick Children. The research project will
have a translational approach, integrating basic molecular mechanisms to clinical outcome.
The investigators hope it will allow the understanding and utilisation of the patient´s own
protective mechanisms, reducing CPB-related injury and ultimately improving patient outcome.
| Status | Completed |
| Enrollment | 51 |
| Est. completion date | March 2015 |
| Est. primary completion date | March 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | N/A to 16 Years |
| Eligibility |
Inclusion Criteria: - Children undergoing cardiac surgery for correction of congenital heart defects utilizing cardiopulmonary bypass and cold blood cardioplegia strategy of myocardial protection. - Children whose parents understand the child's condition, the purpose of the study and are willing to participate. Exclusion Criteria: - Children whose parents either are unwilling or do not have sufficient understanding of the study. - Emergency operations, where there is insufficient time to establish the study protocol. - Premature children presenting a corrected gestational age under 35 weeks. - Presence of extracardiac abnormalities, apart from cases of Down and DiGeorge syndromes which will be included. - Patients with known viral blood infections (e.g. HIV, Hepatitis B) or severe congenital infection. - Patients with severe preoperative brain injury. |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Basic Science
| Country | Name | City | State |
|---|---|---|---|
| United Kingdom | Royal Hospital for Sick Children - Yorkhill | Glasgow |
| Lead Sponsor | Collaborator |
|---|---|
| NHS Greater Glasgow and Clyde |
United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Measurement of the final cardiac injury after cardiopulmonary bypass assessed by markers of cardiac injury and echocardiography. | Echocardiography assessment will take place before surgery, 24 and 48 hours after surgery. Blood markers of cardiac injury: B-type natriuretic peptide and Troponin will be measured before surgery, immediately after surgery, 24 and 48 hours after surgery in order to establish changes in the markers between the mentioned pre and post-operative time points. | Pre and post operatively (immediately before and after surgery, 24 and 48 hours after surgery) | No |
| Secondary | Protein and mRNA expression in the cardiac tissue related to the preconditioning process. | Cardiac tissue will be obtained only from patients who require tissue excision as part of the surgical procedure. Protein and mRNA expression will be assessed after extraction. | Expression assessed at the time of tissue extraction | No |
| Secondary | End organ damage assessment by measurement of markers relevant to lung and kidney function and evaluate a possible benefit from preconditioning. | Blood markers (creatinin, cystatin C, Neutrophil gelatinase associated lipocalin,cGMP and Phosphodiesterase 5)will be measured before surgery, immediately after surgery, 24 and 48 hours after surgery in order to establish changes in the markers between the mentioned pre and post-operative time points. | Pre and post operatively (immediately before and after surgery, 24 and 48 hours after surgery) | No |
| Secondary | Systemic immune response assessment by measurement of inflammatory mediators such as cytokines and nitric oxide metabolites. | Inflammatory blood markers (MDA, isoprostanes, NO metabolites, Cytokines, adhesion molecules, among others)will be measured before surgery, immediately after surgery, 24 and 48 hours after surgery in order to establish changes in the markers between the mentioned pre and post-operative time points | Pre and postoperatively (immediately before and after surgery, 24 and 48 hours after surgery) | No |