Pediatric Remote Ischemic Pre-conditioning Prior to Complex Cardiac Surgery

NCT01739088 | Completed

• 1 other identifier: Pro00032388
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

In 2012, infants having surgery for congenital heart disease have a high survival. The investigators are now focused on improving how sick these infants become after surgery (short term outcomes) and their later neurodevelopment (long term outcomes). During heart surgery, cardiopulmonary bypass (CPB; the heart-lung machine) takes over heart function while the surgeon repairs the heart disease. During this surgery there are periods of time when the amount of blood going to the heart and brain is lower than usual, called "ischemia". Once the surgery is finished the blood going to the heart and brain is increased to normal again, called "reperfusion". This ischemia-reperfusion can cause injury to the heart, brain, and other organs, affecting the short and long term outcomes in these infants. Adult studies have shown that a short time of ischemia to the legs for 5-10 minutes \[the legs are not damaged by a short time of ischemia, unlike the heart or brain\], before severe ischemia to another distant vulnerable vital organ \[like the heart or brain\], can protect this other vital organ from ischemia-reperfusion injury. This is called "remote ischemic preconditioning" (RIPC). Our objective is to test whether RIPC before heart surgery can improve the recovery of the heart and brain after heart surgery in newborn babies with congenital heart disease. The investigators will test whether RIPC will result in lower peak lactate and troponin levels on the day after heart surgery. Lactate levels are a marker for how much the different tissues of the body suffer from ischemia-reperfusion injury. Troponin is released from damaged heart during ischemia-reperfusion. In our trial infants will be randomized to RIPC or control. This means each baby has an equal chance of being in one group or the other. The intervention group will have RIPC before surgery; the "control group" will not. The investigators hope this trial will lead to a larger study to test if RIPC results in fewer days on a breathing machine after surgery, lower mortality, and higher scores on neurodevelopmental tests at 2 years of age.

Conditions

Congenital Heart Disease; Ischemia-reperfusion Injury

Keywords

Congenital heart disease; pediatrics; ischemia-reperfusion injury; long term outcomes

Outcome Measures

Primary Outcomes (1)

• To demonstrate the feasibility of patient recruitment to a remote ischemic pre-conditioning randomized controlled trial at our center

  This is a pilot study looking at feasibility to conduct a larger randomized controlled study on pediatric remote ischemic pre-conditioning at our center.

  One year

Secondary Outcomes (7)

• Troponin I levels

  One year

• Highest inotropic score during the first 24 hours after cardiac surgery

  24 hours after the surgery

• Mechanical ventilation days

  30 days

• Mortality at 30 days

  30 days

• Intensive care unit length of stay

  30 days

Study Arms (2)

Remote ischemic preconditioning stimulus

EXPERIMENTAL

The remote ischemic pre-conditioning arm of the study is the experimental one. Patients in this arm will receive a remote ischemic pre-conditioning stimulus at 24-48 hours pre-operatively, and again intra-operatively before CPB.

Other: Remote ischemic pre-conditioning stimulus.

Sham Ischemic Pre-conditioning

SHAM COMPARATOR

In the control (sham-RIPC) group the cuff will be placed just underneath the upper thigh and the cuff will be inflated for 5 minutes, followed by 5 minutes of cuff deflation, done sequentially for two cycles on each side. In the operating room, after induction of anesthesia, the exact same procedure will be performed in the the control group.

Other: Sham Ischemic Pre-conditioning

Interventions

Remote ischemic pre-conditioning stimulus. OTHER

Forty eight to 24 hours prior to the surgery, patient assigned to remote ischemic pre-conditioning stimulus (RIPC) will have blood pressure cuffs placed on both lower limbs around the upper thigh, and will then have the cuff inflated around the lower limb to a pressure 10 mmHg above systolic blood pressure for 5 minutes, followed by 5 minutes of cuff deflation. This will be done sequentially on each lower limb for two cycles on each limb. In the operating room, after induction of anesthesia, the exact same procedure will be performed in the RIPC group. For each intervention, the legs will be covered by a drape, so that whether the cuff is being inflated around the leg or underneath the leg is not seen by any member of the health care team.

Remote ischemic preconditioning stimulus

Sham Ischemic Pre-conditioning OTHER

In the control (sham Ischemic Pre-conditioning) group 48 to 24 hours prior to the surgery a cuff will be placed just underneath the upper thigh and the cuff will be inflated for 5 minutes, followed by 5 minutes of cuff deflation, done sequentially for two cycles on each side.In the operating room, after induction of anesthesia, the exact same procedure will be performed in the RIPC group.

Sham Ischemic Pre-conditioning

Eligibility Criteria

• Age: Up to 6 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Admitted to the Stollery Children's Hospital Neonatal, Cardiology Unit or Pediatric Intensive Care Unit pre-operative for planned surgical repair of congenital heart disease with cardiopulmonary bypass and aortic cross-clamp
• Age at surgery \<6 weeks old
• Parental consent for enrolment

You may not qualify if:

• Cardio Pulmonary Resuscitation (CPR), Extra-corporeal life support, ECG confirmed myocardial infarction, known chromosomal abnormalities, or known abnormal brain ultrasound (with signs of brain malformation, stroke, or intracranial bleed) pre-operatively
• Gestational age \< 37 weeks
• Known medications that prevent RIPC within 48 hours of surgery, including, naloxone, sulphonylurea hypoglycemic agent, angiotensin receptor blocker, or beta blocker
• Patients not admitted to the Neonatal Intensive Care Unit, Pediatric Intensive Care Unit or Pediatric Cardiology Unit 24 hours before surgery. A brain ultrasound, ECG, and chromosomal analysis are done pre-operatively as a standard of care in our institution

Sponsors & Collaborators

• University of Alberta: lead
• Women and Children's Health Research Institute, Canada: collaborator

Study Sites (1)

Stollery Children's Hospital

Edmonton, Alberta, T6G2B3, Canada

Location

MeSH Terms

Conditions

Heart Defects, Congenital; Reperfusion Injury

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Vascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Gonzalo Garcia Guerra, MD, MSc

  University of Alberta

  PRINCIPAL INVESTIGATOR

• Ari Joffe, MD

  University of Alberta

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: November 27, 2012
• First Posted: November 30, 2012
• Study Start: March 1, 2013
• Primary Completion: March 31, 2017
• Study Completion: March 31, 2017
• Last Updated: May 13, 2019

Record last verified: 2019-05

Locations

CA (1)