The PROTECT-HIE Pilot Trial

NCT07406477 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: Pro00162062
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Some babies experience a lack of oxygen and blood flow around the time of birth. This can lead to a serious condition called hypoxic-ischemic encephalopathy (HIE), which can injure the brain and other organs, including the heart. To reduce brain injury, babies with HIE are treated with therapeutic hypothermia, a standard treatment in which the baby's body temperature is carefully lowered for several days. While cooling helps protect the brain, many babies with HIE still develop heart problems and low blood flow, which may worsen outcomes. Doctors often use medications to support the heart and circulation in these babies, but there is no clear agreement on which medication works best or when it should be started. One commonly used medication is dobutamine, which helps the heart pump more effectively. Dobutamine is already used in newborn intensive care units when babies show signs of heart weakness, but it is usually started only after problems develop. The PROTECT-HIE trial aims to find out whether it is possible and safe to start dobutamine early, before clear signs of heart failure appear, in newborns with HIE who are receiving therapeutic hypothermia. The idea is that early support of the heart may improve blood flow to vital organs, including the brain, and potentially reduce injury. In this study, 40 newborns with HIE will take part at a single neonatal intensive care unit. Babies will be randomly assigned to one of two groups. One group will receive a low, preventative dose of dobutamine within the first four hours after cooling begins. The other group will receive a placebo (an inactive fluid that looks the same). Neither the families nor the medical team assessing outcomes will know which treatment the baby received. The main goal of this study is to determine feasibility-that is, whether starting dobutamine early during cooling can be done reliably and safely in this setting. Researchers will also collect information on important health outcomes, such as signs of brain injury on MRI, seizures, need for additional heart medications, heart function on ultrasound, recovery of blood markers, urine output, length of hospital stay, and survival. Because HIE is an emergency condition and treatment must start very soon after birth, parents will be approached for consent after the baby has been stabilized. This approach is commonly used in neonatal emergency research and has been approved in similar studies. The results of this study will help determine whether a larger trial should be done in the future. Ultimately, this research aims to improve care and outcomes for babies affected by HIE by optimizing support for the heart during a critical period after birth.

Conditions

Hypoxic-ischemic Encephalopathy (HIE)

Keywords

Hypoxic-ischemic encephalopathy; feasibility RCT; neonatal cardiac dysfunction; prophylactic inotrope; therapeutic hypothermia; neonatal HIE; dobutamine

Outcome Measures

Primary Outcomes (1)

• Feasibility/Safety

  Proportion of eligible infants receiving the intervention (or placebo) within 4 hours of initiating TH

  At 24 hours of age

Secondary Outcomes (12)

• Brain injury

  through study completion, an average of 1 month

• Severity and type of brain injury

  through study completion, an average of 1 month

• Mortality

  through study completion, an average of 1 month

• Seizure activity

  through study completion, an average of 1 month

• Need for escalation the inotropic support

  through study completion, an average of 1 month

Study Arms (2)

Dobutamine group

EXPERIMENTAL

If randomized to the prophylaxis/dobutamine arm, dobutamine will be administered at a dose of 10 mcg/kg/min via intravenous access within 4 hours of initiating TH. As a part of standard care for HIE, a central umbilical venous access is routinely acquired whenever possible. We will use the dobutamine concentration of 2000 mcg/ml. The infusion will be prepared in dextrose 5% solution in 50 mL bags. Dobutamine monograph is attached to the protocol as well (Appendix F). The infusion will be continued until either weaned by the clinical team, escalation of inotropic support, or improvement of clinical situation to allow weaning of dobutamine.

Drug: Dobutamine; Diagnostic Test: TnECHO

Control group

PLACEBO COMPARATOR

Infants randomized to the placebo arm will receive an inert preparation containing no active pharmacologic agent. The placebo will be identical in appearance, volume, and method of administration to the active intervention and will be administered according to the same dosing schedule and duration. We will use dextrose 5% (as placebo), which will be started within 4 hours of initiating TH. The infusion will be continued until either weaned by the clinical team, escalation of inotropic support, or improvement of clinical situation to allow weaning of dobutamine.

Diagnostic Test: TnECHO

Interventions

Dobutamine DRUG

If randomized to the prophylaxis/dobutamine arm, dobutamine will be administered at a dose of 10 mcg/kg/min via intravenous access within 4 hours of initiating TH. As a part of standard care for HIE, a central umbilical venous access is routinely acquired whenever possible. We will use the dobutamine concentration of 2000 mcg/ml. The infusion will be prepared in dextrose 5% solution in 50 mL bags. Dobutamine monograph is attached to the protocol as well (Appendix F). The infusion will be continued until either weaned by the clinical team, escalation of inotropic support, or improvement of clinical situation to allow weaning of dobutamine.

Dobutamine group

TnECHO DIAGNOSTIC_TEST

In both groups, 2 TnECHOs will be performed. TnECHO T1 will be performed within the 24 hours of randomization, and TnECHO T2 will be performed within 24-48 hours after TnECHO T1. All echocardiographic assessments are done by physicians trained in TnECHO or by pediatric cardiology team. Echocardiographic assessment will be performed as per the American Society or Echocardiography guidelines(63-66). Details of the standardised echo views and measurements are outlined in Appendix B.

Control group; Dobutamine group

Eligibility Criteria

• Age: 1 Day - 1 Day
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Newborns with hypoxemic ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH).

You may not qualify if:

• Congenital abnormality
• known contraindication of dobutamine
• Left ventricular outflow tract dynamic obstruction
• Hypersensitivity to dobutamine
• Uncorrected tachyarrhythmias or ventricular fibrillation
• Newborns who are already started on inotropes at the time of randomization.
• Parental refusal to consent to participate

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

Royal Alexandra Hospital

Edmonton, Alberta, Canada

Location

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain

Interventions

Dobutamine

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

Intervention Hierarchy (Ancestors)

Catecholamines; Amines; Organic Chemicals; Phenethylamines; Ethylamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Central Study Contacts

Aimann Surak, MD FRCPC

CONTACT

780-735-4647; aimann@ualberta.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 29, 2026
• First Posted: February 12, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2029
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)