Hypoxic-Ischemic EncephalopathyNCT05379218
RIC in HIE: A Safety and Feasibility Trial
A study testing Remote Ischemic Conditioning in people with Hypoxic-Ischemic Encephalopathy, run by The Hospital for Sick Children at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hypoxic-Ischemic Encephalopathy
- What is being tested?
- Remote Ischemic Conditioning
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteCanada
- Study dates
- 17 Jan 2022to 5 Feb 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Qualifying for therapeutic hypothermia according to the primary care team based on the current SickKids HIE Protocol
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Remote Ischemic Conditioning in Hypoxic-Ischemic Encephalopathy: A Safety and Feasibility Trial
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.
Read the detailed description
Hypoxic-ischemic encephalopathy (HIE) is a devastating condition in which newborn infants are deprived of oxygen in the peripartum period, resulting in brain injury. HIE is a leading cause of infant morbidity and mortality worldwide. Within the last 15 years, the introduction of hypothermia as a therapy for HIE has revolutionized our care of these vulnerable infants, but despite these improvements, nearly 50% of infants die or have major disability at 18 months. Therefore, there is a significant need to develop novel adjunctive therapies for HIE.
Remote ischemic conditioning (RIC) is a procedure that involves the application of brief cycles of non-lethal ischemia and reperfusion to a remote site, with the goal of protecting distant organs exposed to ischemic injury. RIC has been extensively studied in experimental models and applied clinically in adults, children, and neonates. In neonates, there have been trials exploring its potential role before cardiac surgery and necrotizing enterocolitis. Most of these studies performed up to 4 cycles of 5 minutes of ischemia in a single day and found RIC to be feasible and safe. Experimental studies suggest that RIC, acting through three inter-related mechanisms (neural, humoral, and systemic pathways) is associated with increased cerebral blood flow, decreased inflammation, and enhanced cell survival. RIC has been studied as a potential treatment in adult stroke, and while the evidence to date is inconclusive, preliminary data suggest that RIC may reduce the size and the severity of the stroke lesion, as well as improve cognitive outcomes.
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. In this proposal, we outline a carefully designed and conducted early phase study of RIC in neonates with HIE.
- Conditions
- Hypoxic-Ischemic Encephalopathy
- Being tested
- Remote Ischemic Conditioning
- Keywords
- Hypoxic-Ischemic Encephalopathy
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote Ischemic ConditioningDevice
Patients randomized to the RIC arm, cohorts of 4 consecutive patients will receive escalating therapy:
- 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.
- 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.
- 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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention Arm - Remote Ischemic Conditioning | Experimental | Remote Ischemic Conditioning Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
RIC cycles administered as planned (Y/N)
Designated RIC cycles are administered as planned (dichotomous variable)
Measured: 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
Measured: 72 hours
Secondary outcomes (2)
Number of patients with cutaneous injury
New-onset of skin breakdown, bruising, ecchymosis or petechiae, within 24 hours after the end of the maneuver (comparing to the previous baseline assessment)
Measured: 24 hours
Number of patients with transient and persistent pain defined as a premature infant pain profile (PIPP) score >7
Pain measured by PIPP score > 7 will be considered as an episode of pain. A patient will be considered to have persistent pain if PIPP score is higher than the baseline score 6 hours after the maneuver.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2022
- Study start17 Jan 2022
- Primary completion5 Feb 2024
- Study completion5 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypoxic-Ischemic EncephalopathyStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian Kalish, The Hospital for Sick Children
- Investigators
- Brian Kalish, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05379218
- Sponsor's protocol ID
- 1000077295
- Status last verified
- Mar 2024
- First submitted
- 25 Nov 2021
- Last updated
- 7 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Remote Ischemic Conditioning in Hypoxic-Ischemic Encephalopathy: A Safety and Feasibility Trial
- ClinicalTrials.gov ID
- NCT05379218
- Acronym / sponsor ID
- 1000077295
- Conditions
- Hypoxic-Ischemic Encephalopathy
- Keywords
- Hypoxic-Ischemic Encephalopathy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- 17 Jan 2022 (actual)
- Primary completion
- 5 Feb 2024 (actual)
- Study completion
- 5 Feb 2024 (actual)
- First posted
- 18 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Hypoxic-ischemic encephalopathy (HIE) is a devastating condition in which newborn infants are deprived of oxygen in the peripartum period, resulting in brain injury. HIE is a leading cause of infant morbidity and mortality worldwide. Within the last 15 years, the introduction of hypothermia as a therapy for HIE has revolutionized our care of these vulnerable infants, but despite these improvements, nearly 50% of infants die or have major disability at 18 months. Therefore, there is a significant need to develop novel adjunctive therapies for HIE.
Remote ischemic conditioning (RIC) is a procedure that involves the application of brief cycles of non-lethal ischemia and reperfusion to a remote site, with the goal of protecting distant organs exposed to ischemic injury. RIC has been extensively studied in experimental models and applied clinically in adults, children, and neonates. In neonates, there have been trials exploring its potential role before cardiac surgery and necrotizing enterocolitis. Most of these studies performed up to 4 cycles of 5 minutes of ischemia in a single day and found RIC to be feasible and safe. Experimental studies suggest that RIC, acting through three inter-related mechanisms (neural, humoral, and systemic pathways) is associated with increased cerebral blood flow, decreased inflammation, and enhanced cell survival. RIC has been studied as a potential treatment in adult stroke, and while the evidence to date is inconclusive, preliminary data suggest that RIC may reduce the size and the severity of the stroke lesion, as well as improve cognitive outcomes.
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. In this proposal, we outline a carefully designed and conducted early phase study of RIC in neonates with HIE.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention Arm - Remote Ischemic Conditioning | Experimental | Device: Remote Ischemic ConditioningRemote 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Qualifying for therapeutic hypothermia according to the primary care team based on the current SickKids HIE Protocol
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Remote Ischemic ConditioningPatients 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. | Device | Intervention Arm - Remote Ischemic Conditioning |
Primary outcome
RIC cycles administered as planned (Y/N)
Time frame: 72 hours
Designated RIC cycles are administered as planned (dichotomous variable)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 72 hours
Frequency of limb ischemia, incidence of RIC interruption and rescue intervention, incidence of subcutaneous fat necrosis, incidence of acute kidney injury, mortality
2 secondary outcomes
Number of patients with cutaneous injury
Time frame: 24 hours
Number of patients with transient and persistent pain defined as a premature infant pain profile (PIPP) score >7
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2024.
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Levetiracetam as an Adjuvant Therapy to Hypothermia in Neonatal Asphyxia
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Minimal Sedation Versus Standard Continuous Sedation After Out-of-Hospital Cardiac Arrest
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Neuro-MoD: Neuroplasticity With Motor Development
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian Kalish, MD principal investigator
The Hospital for Sick Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Remote Ischemic Conditioning in people with Hypoxic-Ischemic Encephalopathy, run by The Hospital for Sick Children at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
RIC cycles administered as planned (Y/N) (time frame: 72 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2024.