RIC in HIE: A Safety and Feasibility Trial

NCT05379218 | Completed DMC

• 1 other identifier: 1000077295
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Remote Ischemic Conditioning has never been studied in neonates with HIE. However, RIC has been studied in animal models of perinatal asphyxia and has shown encouraging results. In neonatal rats with HIE, RIC is associated with reduced sensory motor deficits compared to non-RIC, and repeated cycles in three consecutive days is superior to a single treatment. In piglets, four cycles of 10 minutes of bilateral hindlimb ischemia immediately after bilateral common carotid occlusion results in reduced cell death in the periventricular white matter and internal capsule. These preclinical studies support the hypothesis that RIC may be beneficial in infants with HIE.

Conditions

Hypoxic-Ischemic Encephalopathy

Keywords

Hypoxic-Ischemic Encephalopathy

Outcome Measures

Primary Outcomes (2)

• RIC cycles administered as planned (Y/N)

  Designated RIC cycles are administered as planned (dichotomous variable)

  72 hours

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Frequency of limb ischemia, incidence of RIC interruption and rescue intervention, incidence of subcutaneous fat necrosis, incidence of acute kidney injury, mortality

  72 hours

Secondary Outcomes (2)

• Number of patients with cutaneous injury

  24 hours

• Number of patients with transient and persistent pain defined as a premature infant pain profile (PIPP) score >7

  24 hours

Other Outcomes (6)

• aEEG

  4 hours

• Biomarkers

  72 hours

• MRI including diffusion-weighted imaging and spectroscopy

  7 days

Study Arms (2)

Intervention Arm - Remote Ischemic Conditioning

EXPERIMENTAL

Remote Ischemic Conditioning

Device: Remote Ischemic Conditioning

Control Arm - No Remote Ischemic Conditioning

NO INTERVENTION

No intervention. A blood pressure cuff will be placed on the infant's arm but will not be inflated.

Interventions

Remote Ischemic Conditioning DEVICE

Patients randomized to the RIC arm, cohorts of 4 consecutive patients will receive escalating therapy: A. 4 consecutive patients will undergo 4 cycles of 3 minutes ischemia, followed by 5 minutes reperfusion, on Day 1 of therapeutic hypothermia B. Observing no safety events (see below) from patients in group A, 4 consecutive patients will undergo 4 cycles of 5 minutes ischemia, followed by 5 minutes reperfusion, on Day 1 of therapeutic hypothermia. C. Observing no safety events from patients in group B, 4 consecutive patients will undergo 4 cycles of 5 minutes ischemia, followed by 5 minutes reperfusion, on Days 1 and 2 of therapeutic hypothermia. D. Observing no safety events from patients in group C, 4 consecutive patients will undergo 4 cycles of 5 minutes ischemia, followed by 5 minutes reperfusion, on Days 1, 2, and 3 of therapeutic hypothermia. All infants will have an extra 1ml of blood collected.

Intervention Arm - Remote Ischemic Conditioning

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Qualifying for therapeutic hypothermia according to the primary care team based on the current SickKids HIE Protocol

You may not qualify if:

• Gestational age \<35 weeks
• Known central nervous system malformations
• Known chromosomal or genetic anomalies
• Confirmed or suspected inborn error of metabolism
• Parental decision for withdrawal of life-sustaining treatment ("comfort care"). If this decision is made after enrollment but before completion of RIC intervention, no further study-related intervention will be performed.
• Patients requiring significant hemodynamic support (two or more agents for blood pressure support, \>0.05mcg/kg/min epinephrine infusion, or \>0.1 mU/kg/min vasopressin) for the four hour period prior to RIC
• Patients requiring inhaled nitric oxide or fraction of inspired oxygen (FiO2) \>50% for the four-hour period prior to RIC

Sponsors & Collaborators

• The Hospital for Sick Children: lead

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Brian Kalish, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neonatologist

Study Record Dates

• First Submitted: November 25, 2021
• First Posted: May 18, 2022
• Study Start: January 17, 2022
• Primary Completion: February 5, 2024
• Study Completion: February 5, 2024
• Last Updated: March 7, 2024

Record last verified: 2024-03

Locations

CA (1)