Remote Ischaemic Preconditioning in Children Undergoing Cardiac Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by NHS Greater Glasgow and Clyde
Sponsor:
Information provided by (Responsible Party):
Maribel Verdesoto, University of Glasgow
ClinicalTrials.gov Identifier:
NCT01680601
First received: August 29, 2012
Last updated: February 18, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention
Ischaemic Reperfusion Injury
Procedure: Remote ischaemic preconditioning (RIPC)
Procedure: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: Effect of Remote Ischaemic Preconditioning in Cardiac Dysfunction and End-organ Injury Following Cardiac Surgery With Cardiopulmonary Bypass in Children.

Resource links provided by NLM:


Further study details as provided by NHS Greater Glasgow and Clyde:

Primary Outcome Measures:
  • Measurement of the final cardiac injury after cardiopulmonary bypass assessed by markers of cardiac injury and echocardiography. [ Time Frame: Pre and post operatively (immediately before and after surgery, 24 and 48 hours after surgery) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Protein and mRNA expression in the cardiac tissue related to the preconditioning process. [ Time Frame: Expression assessed at the time of tissue extraction ] [ Designated as safety issue: No ]
    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.

  • End organ damage assessment by measurement of markers relevant to lung and kidney function and evaluate a possible benefit from preconditioning. [ Time Frame: Pre and post operatively (immediately before and after surgery, 24 and 48 hours after surgery) ] [ Designated as safety issue: No ]
    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.

  • Systemic immune response assessment by measurement of inflammatory mediators such as cytokines and nitric oxide metabolites. [ Time Frame: Pre and postoperatively (immediately before and after surgery, 24 and 48 hours after surgery) ] [ Designated as safety issue: No ]
    Inflammatory blood markers (MDA, isoprostanes, NO metabolites, Cytokines, addhession 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


Estimated Enrollment: 80
Study Start Date: January 2013
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RIPC group
Patients assigned to this arm will go through a remote ischaemic preconditioning (RIPC)protocol
Procedure: Remote ischaemic preconditioning (RIPC)
RIPC will be performed by 3 cycles of 5 minute leg ischaemia induced by inflation of a blood pressure cuff to 40 mmHg above the patient's systolic pressure. This protocol will be performed at two phases: 24 hours before surgery and during anaesthesia immediately prior to surgery.
Placebo Comparator: Control
Patients assigned to this arm will not receive the intervention, however the protocol will be applied to a wooden block in order to maintain blinding to relatives and investigators.
Procedure: Placebo

  Eligibility

Ages Eligible for Study:   up to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01680601

Contacts
Contact: Maribel C Verdesoto, Medic +44 07504783528 m.verdesoto-rodriguez.1@research.gla.ac.uk

Locations
United Kingdom
Royal Hospital for Sick Children - Yorkhill Recruiting
Glasgow, United Kingdom, G3 8SJ
Contact: Maribel C Verdesoto       m.verdesoto-rodriguez.1@research.gla.ac.uk   
Principal Investigator: Maribel C Verdesoto         
Sponsors and Collaborators
NHS Greater Glasgow and Clyde
  More Information

No publications provided

Responsible Party: Maribel Verdesoto, PhD student, University of Glasgow
ClinicalTrials.gov Identifier: NCT01680601     History of Changes
Other Study ID Numbers: GN12KH253
Study First Received: August 29, 2012
Last Updated: February 18, 2013
Health Authority: United Kingdom - Scotland: NHS Greater Glasgow and Clyde, Research & Development

Additional relevant MeSH terms:
Ischemia
Reperfusion Injury
Wounds and Injuries
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications

ClinicalTrials.gov processed this record on August 21, 2014