DEX vs SEVO in Congenital Heart Surgery (DEXLOSNeuro)

Effect of DEXmedetomidine and LOw Dose Sevoflurane on the Release of Serum Neurofilament Light in Congenital Cardiac Surgery.

Anesthesia-related neurotoxicity in the developing brain is still a concern although evidence in humans is debatable. Moreover, it is unclear whether repeated and/or prolonged exposures are harmless and whether their effects are more pronounced in newborns and infants with brains more vulnerable to injury. One such specific group of patients is children with congenital heart disease (CHD). Nearly, half of the school-age survivors with CHD exhibit neurodevelopmental symptoms. It is thus important to elucidate whether any plausible neurotoxicity of the commonly used anesthetic agents can be observed in this population, and whether specific neuroprotective strategies can be demonstrated within the frame of a randomized controlled trial (RCT).

Animal data have shown that dexmedetomidine (DEX) induces neuroprotective effects only at well-adjusted doses. One major issue with trials of anesthetic neurotoxicity is the latency between the conduct of these studies and the assessment of neurodevelopmental outcome. In contrast, the use of biomarkers of neuronal injury could be extremely valuable. Serum Neurofilament Light (NfL) has been shown to be a sensitive and specific marker of neuronal injury and is associated with neurologic outcome of children with various pathologies. The investigators hypothesize that in congenital heart surgery, use of DEX as main anesthetic agent in conjunction with low dose sevoflurane results in less release of serum NfL and is thus potentially less neurotoxic compared to the current standard of care. The hypothesis is tested with a RCT including patients between 0 - 3y undergoing surgery with cardiopulmonary bypass. To avoid any neurotoxicity due to anesthetic overdose, intraoperative burst suppression will be avoided. In addition to postoperative comparison of serum NfL, postoperative electroencephalogram and neurodevelopmental outcome of both groups will be compared taking into consideration the genetic background.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Defects, Congenital
• Intervention / Treatment: Drug: DEX group; Other: Control group

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mona Momeni, MD, PhD; Phone Number: 003227647029; Email: mona.momeni@uclouvain.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients up to 3 years
• Must undergo cardiac surgery with CPB

Exclusion Criteria:

• Preoperative chronic kidney disease (glomerular filtration rate of less than 30 ml/min per 1.73m2 for greater than 3 months)
• Preoperative cerebral hemorrhage, stroke or
• Preoperative seizures
• Abnormal preoperative cerebral ultrasound
• Preoperative Extracorporeal Life Support
• Preoperative sedated and intubated patients
• Preterm newborns (< 32 W gestational age)
• Newborns weighing < 2 kg
• Patients with Williams-Beuren syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DEX group; Participants will receive an intraoperative and postoperative DEX infusion. In addition a low dose of sevoflurane will be administered.	Drug: DEX group; Participants will receive a dexmedetomidine infusion in addition to low dose sevoflurane anesthesia.
Active Comparator: Control group; Participants will receive general anesthesia with sevoflurane according to institutinal's practice.	Other: Control group; Participants will receive general anesthesia based on institutional's practice with commonly used doses of sevoflurane.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of serum Neurofilament Light	To show a difference of change in serum NfL concentrations between both groups at 24h compared to baseline values.	At 24 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of serum Neurofilament Light		Baseline before start of anesthesia
Concentration of serum Neurofilament Light		Start of cardiopulmonary bypass
Concentration of serum Neurofilament Light		At 72 hours postoperatively
Concentration of serum Neurofilament Light		At postoperative day 5
Neurodevelopmental outcome testing	Bailey Scales of Infant and Toddler Development - Third Edition. Higher scores are better.	3 months postoperatively
Neurodevelopmental outcome testing	Bailey Scales of Infant and Toddler Development - Third Edition. Higher scores are better.	6 months postoperatively
Postoperative electroencephalogram registration	Number of seizures	24 hours
Dose of Analgesics	Use and dose of analgesics	72 hours postoperatively
Renal function	Defined by pediatric RIFLE criteria	7 days postoperatively
Concentration of regional cerebral oxygenation	Area Under Curve of time spent below rSO2 levels of 50%; Area Under Curve of time spent below baseline rSO2 levels	Intraoperatively
Postoperative electroencephalogram registration	Number of burst-suppression episodes	24 hours
Postoperative electroencephalogram registration	Duration of burst-suppression episodes	24 hours
Postoperative electroencephalogram registration	Duration of seizures	24 hours
Time of exsudation	time to extubation	7 days postoperatively
Pediatric Intensive Care Unit stay	Duration of stay in Pediatric Intensive Care Unit	Up to 24 weeks
Hospital stay	Days of hospital stay	Up to 24 weeks

Collaborators and Investigators

• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Investigators: Principal Investigator: Mona Momeni, MD, PhD, Cliniques Universitaires Saint-Luc

Study record dates

Study Major Dates

• Study Start (Anticipated): January 5, 2023
• Primary Completion (Anticipated): December 30, 2025
• Study Completion (Anticipated): June 30, 2026

Study Registration Dates

• First Submitted: April 21, 2022
• First Submitted That Met QC Criteria: May 6, 2022
• First Posted (Actual): May 11, 2022

Study Record Updates

• Last Update Posted (Actual): September 23, 2022
• Last Update Submitted That Met QC Criteria: September 20, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiovascular Abnormalities; Congenital Abnormalities; Heart Defects, Congenital
• Other Study ID Numbers: Ethical Advice

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No