Overview

Conditions complication of anesthesia, ischaemia-reperfusion injury
Treatments dexmedetomidine, 0.9% nacl
Phase phase 4
Sponsor The Hospital for Sick Children
Start date November 2014
End date December 2017
Trial size 36 participants
Trial identifier NCT02299063, 1000044746

Summary

The investigators hypothesize that in addition to a known sympatholytic effect, intraoperative dexmedetomidine reduces adverse changes in mitochondrial function and structure attenuating ischaemia-reperfusion and end-organ injury for children with non cyanotic congenital heart defects having corrective heart surgery.

Recruiting in the following locations…

United States No locations recruiting
Other Countries Canada

Study Design

Allocation randomized
Endpoint classification pharmacodynamics study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose prevention
Arm
(Placebo Comparator)
0.9% Saline: bolus dose of 0.125mL/kg infused over 10 minutes, followed by a continuous infusion (CI) dose at 0.15mL/kg/hr for the duration of surgery.
0.9% nacl Normal Saline
(Experimental)
Dexmedetomidine: bolus dose of 0.5 mcg/kg infused over 10 minutes, followed by a continuous infusion (CI) dose at 0.6 mcg/kg/hr for the duration of surgery.
dexmedetomidine Precedex
A bolus dose of 0.5 mcg/kg infused over 10 minutes will be administered, followed by a continuous infusion for the duration of the surgery at 0.6 mcg/kg/hr.

Primary Outcomes

Measure
Mitochondrial function (use high content imaging (HCI)
time frame: Intraoperative

Secondary Outcomes

Measure
Creatinine level (Marker of acute renal injury)
time frame: Postoperative day 1
Cardiac function (Left ventricular ejection fraction measured by trans-thoracic echocardiography)
time frame: Postoperative day 1
Inotropes and vasopressors (Duration and dose of inotropes and vasopressors after surgery)
time frame: Postoperative day 1

Eligibility Criteria

Male or female participants from 3 months up to 36 months old.

Inclusion Criteria: - aged between 3 - 36 months - having primary corrective heart surgery Exclusion Criteria: - recent surgery (< 3 months) - previous chemotherapy - previous transfusion of blood products - neurodevelopmental disorders (including Trisomy 21) - supplemental oxygen requirement (< 3 months) - asthma requiring regular therapy - obstructive sleep apnea - the presence of concurrent infection or inflammation - a known allergy to dexmedetomidine hydrochloride

Additional Information

Official title The Protective Effect of the α2-agonist Dexmedetomidine on Mitochondrial Structure and Function for Children With Non-cyanotic Congenital Heart Defects Having Cardiac Surgery: A Randomized Controlled Trial.
Principal investigator James D O'Leary, MBBCh
Description PICO: For children with non cyanotic congenital heart defects having corrective heart surgery (P) does intraoperative dexmedetomidine (I) reduce real-time changes in mitochondrial function and content (O) compared with children not receiving dexmedetomidine (C). The study drug (dexmedetomidine or placebo) will be mixed in a standardized syringe of 4mcg/mL for active syringes or 50mL 0.9% sodium chloride for placebo. Blinded syringes will be prepared by the Research Support Pharmacy. Administration is via the existing central venous line. A bolus dose of 0.125mL/kg (0.5 mcg/kg dexmedetomidine) infused over 10 minutes will be administered, followed by a continuous infusion for the duration of the surgery. The dexmedetomidine/placebo continuous infusion (CI) dose will run at 0.15mL/kg/hr (0.6 mcg/kg/hr dexmedetomidine). Blood samples will be obtained from each child at three points in the operating room: 1) after the induction of anesthesia, 2) at the first separation from CPB (prior to administration of blood products), and 3) at the end of the surgery. Samples obtained will be analyzed for mitochondrial function and morphology, total cellular mitochondrial biomass, and mitochondrial deoxyribonucleic acid (mtDNA) damage: 1. After isolating lymphocytes, we will use high content imaging (HCI) to assess mitochondrial function and morphology. The lymphocytes will be stained with tetramethylrhodamine methyl ester (TMRM), which stains mitochondria in proportion to mitochondrial membrane potential, giving a metric for mitochondrial function. In addition, the cells will be stained with MitoTracker Green®, which can be used to assess mitochondrial morphology. Mitochondrial morphology will be quantified in a non-biased fashion using a mathematical image analysis algorithm. 2. After extraction of genomic DNA, total cellular mitochondrial biomass and mitochondrial DNA damage will be measured using traditional and long-patch quantitative polymerase chain reaction (PCR). Myocardial tissue will be also collected prior to closure of the atriotomy. Samples will be placed into 3% buffered glutaraldehyde at the time of biopsy, and imaging of mitochondrial structure using electron microscopy will be performed.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by The Hospital for Sick Children.