Can early support of heart function improve outcomes in newborn infants receiving cooling treatment for hypoxic-ischemic encephalopathy?
Prophylactic Therapy to Enhance Cardiovascular Treatment in Neonatal Hypoxic-Ischemic Encephalopathy
Background
Hypoxic-ischemic encephalopathy (HIE) is a brain injury caused by insufficient oxygen and blood flow around birth. Affected infants may also develop impaired heart function and circulation. PROTECT-HIE will investigate whether early administration of dobutamine, a medication that supports heart function, is feasible and safe during therapeutic hypothermia (cooling treatment).
Population
Newborn infants with HIE receiving therapeutic hypothermia.
Primary Objective
To assess the feasibility of starting prophylactic dobutamine within four hours of commencing therapeutic hypothermia and delivering the intervention according to the study protocol.
Research Question: Population, Intervention, Comparison, Outcome and Timeline
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Population: Newborn infants with HIE undergoing therapeutic hypothermia.
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Intervention: Intravenous dobutamine at 10 micrograms/kg/min.
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Comparison: A matching placebo infusion containing 5% dextrose.
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Outcomes: Recruitment, protocol adherence and safety, with exploratory assessment of brain injury and other hospital outcomes.
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Timeline: Study infusion initiated within four hours of starting therapeutic hypothermia, with follow-up until hospital discharge or death.
Design and Sample Size
Single-centre, double-blind, randomized, placebo-controlled pilot trial involving 40 infants, with 20 allocated to each group.
Eligibility Criteria
Newborn infants with HIE receiving therapeutic hypothermia who have not received vasoactive or inotropic medications before randomization.
Infants with congenital anomalies or underlying conditions that contraindicate dobutamine administration will be excluded.
Primary Outcomes
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Recruitment and initiation of the allocated intervention within the specified window in more than 60% of eligible infants.
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Protocol adherence in more than 75% of randomized infants.
Secondary Outcomes
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Presence, severity and pattern of brain injury on magnetic resonance imaging (MRI).
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In-hospital mortality and seizures.
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Need for additional medications to support heart function or circulation.
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Ultrasound measures of heart function and pulmonary circulation.
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Time to normalization of blood lactate.
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Duration of inhaled nitric oxide treatment, when required.
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Urine output and length of hospital stay.
Safety Monitoring
Adverse events will be monitored throughout the study. An independent Data Safety Monitoring Board will review participant safety.
Parental Consent
Written parental or legal guardian consent will be sought before enrolment whenever feasible. When the time-sensitive intervention prevents prospective consent, an approved deferred-consent process will be followed, with families approached as soon as reasonably feasible.
Analysis
The study will primarily assess feasibility and inform the design of a larger trial. Comparisons of clinical outcomes will be exploratory.
Study Centre
Philip C. Etches Neonatal Intensive Care Unit, Royal Alexandra Hospital, University of Alberta, Edmonton, Canada.
Planned Recruitment Period: 36 months.
Investigators: Dr. Aimann Surak and Professor Georg M. Schmölzer.
ClinicalTrials.gov: NCT07406477