Caffeine for Hypoxic Ischemic Encephalopathy

Summary

CHIME is a randomized, parallel-arm, double-blind, placebo-controlled trial focused on infants with hypoxic ischemic encephalopathy (HIE). The trial will recruit neonates who are diagnosed with HIE within six hours after birth based on physiologic criteria (acidosis noted on an umbilical cord or early \[\<1 hour\] postnatal blood sample) and neurologic criteria (modified Sarnat exam consistent with encephalopathy). Following informed consent, and by six hours after birth, neonates with HIE will be randomized to one of two treatment arms and subsequently receive one 20 mg/kg dose of oral caffeine followed by two additional 10 mg/kg doses at 24-hour intervals or placebo of the same regimen (three total doses).

The goal of this clinical trial is to compare the incidence of all-cause mortality OR moderate to severe neurodevelopmental impairment (NDI) at 18-22 months between neonates with HIE who are randomized to oral caffeine or placebo. Our hypothesis is that neonates with HIE who receive oral caffeine will have 10% lower incidence of all-cause mortality or moderate to severe NDI at 18-22 months compared to placebo.

Conditions

• Hypoxic Ischemic Encephalopathy (HIE)

Interventions

DRUG

Caffeine citrate oral solution

Caffeine citrate oral solution will be used and administered by enteral route (oral or by gavage tube). The loading dose (20 mg/kg) will be administered once followed by daily doses of 10 mg per kg body weight every 24 hours for two doses. The study Standard Operating Procedures (SOPs) includes details regarding caffeine preparation based on the participant's body weight.

DRUG

Oral placebo solution

Identical placebo oral solution

Sponsors & Collaborators

• RTI International

  collaborator OTHER

• University of North Carolina, Chapel Hill

  collaborator OTHER

• Kinshasa School of Public Health

  collaborator OTHER

• Institute of Nutrition of Central America and Panama (INCAP)

  collaborator UNKNOWN

• Lata Medical Research Foundation, Nagpur

  collaborator OTHER

• Aga Khan University

  collaborator OTHER

• University Teaching Hospital, Lusaka, Zambia

  collaborator OTHER

• KLE Academy of Higher Education and Research (Deemed- to- be-University), Jawaharlal Nehru Medical College (JNMC), Belagavi, India

  collaborator UNKNOWN

• Bill and Melinda Gates Foundation

  collaborator OTHER

• University of Virginia

  collaborator OTHER

• University of Alabama at Birmingham

  collaborator OTHER

• Thomas Jefferson University

  collaborator OTHER

• Columbia University

  collaborator OTHER

• University of Colorado, Denver

  collaborator OTHER

• International Centre for Diarrhoeal Disease Research, Bangladesh

  collaborator OTHER

• NICHD Global Network for Women's and Children's Health

  lead NETWORK

Principal Investigators

• Melissa Bauserman, MD, MPH · University of North Carolina, Chapel Hill

• Elizabeth M McClure, PhD · RTI International

• Denise C Babineau, PhD · RTI International

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Max Age

6 Hours

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-06-30

Primary Completion

2029-12-31

Completion

2030-07-31

Countries

• Bangladesh
• Democratic Republic of the Congo
• Guatemala
• India
• Pakistan
• Zambia

Study Locations