Caffeine for Hypoxic Ischemic Encephalopathy

NCT06855108 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: CP CHIMEINV-068776
• Study Type: interventional
• Target: 830
• Locations: 6 countries
• Sites: 7

Brief 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)

Keywords

Caffeine; Hypoxic Ischemic Encephalopathy; HIE; AKI

Outcome Measures

Primary Outcomes (1)

• Composite outcome, defined by the occurrence of any of the following:

  All-cause infant mortality or moderate to severe neurodevelopmental impairment

  18-22 months

Secondary Outcomes (20)

• Secondary composite outcome, defined by the occurrence of any of the following:

  18-22 months

• All-cause neonatal mortality

  28 days after delivery

• All-cause infant mortality

  12 months

• All-cause mortality

  18 months

• Time to all-cause mortality

  18-22 months

Study Arms (2)

Caffeine citrate oral solution

EXPERIMENTAL

Participants randomized to the oral caffeine arm will receive a single 20 mg/kg loading dose of caffeine citrate administered enterally within 6 hours after delivery, followed by a 10 mg/kg dose every 24 hours for two additional doses.

Drug: Caffeine citrate oral solution

Oral placebo

PLACEBO COMPARATOR

Participants randomized to the oral placebo arm will receive a single identical placebo administered enterally within 6 hours after delivery, followed by an identical placebo dose every 24 hours for two additional doses.

Drug: Oral placebo solution

Interventions

Caffeine citrate oral solution DRUG

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.

Caffeine citrate oral solution

Oral placebo solution DRUG

Identical placebo oral solution

Also known as: Oral placebo

Oral placebo

Eligibility Criteria

• Age: Up to 6 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infants who meet all the following criteria are eligible for enrollment as study participants:
• Liveborn infants ≥36 weeks
• Birth weight ≥1800 grams
• Meets physiologic criteria for moderate to severe HIE, defined as meeting either of the following two criteria:
• Criterion #1: Severe acidosis, defined as an umbilical cord sample or neonatal serum sample within one hour after birth demonstrating any of following criteria:
• pH \<7.0; or
• Base Deficit ≥16 mmol/L; or
• Lactate \>8 mmol/L.
• Criterion #2: Participant must meet all of the following three criteria:
• i. Moderate acidosis, defined as an umbilical cord sample or neonatal serum sample within one hour after birth demonstrating any of following criteria:
• POC pH 7.0-7.15; or
• Base Deficit 10.0-15.9 mmol/L; or
• Lactate 6-8 mmol/L.
• ii. Evidence of an acute perinatal event (i.e., placental abruption, intrapartum hemorrhage, cord prolapse, severe fetal heart rate abnormality, uterine rupture).
• iii. Any of the following criteria:

You may not qualify if:

• Infants who meet any of the following criteria are not eligible for enrollment as study participants:
• Home births
• Infants who cannot be enrolled, randomized and receive study medication within 6 hours post-delivery
• Infants with a recognized major congenital anomaly or genetic syndrome that would affect their neurodevelopment.
• Infants for whom medical care will not be provided based on the severity of their condition or any other condition that would preclude participation per clinical judgement.
• Infant has received therapeutic hypothermia or there is a clinical plan to initiate active or passive hypothermia for the infant.
• Infants who will be unavailable to complete follow-up visits.
• Infants who have received caffeine after delivery.
• Infants whom the health care team deem ineligible for the study based on likelihood to receive caffeine outside of the study protocol.
• Enrollment in another trial that will impact participation in this trial.

Sponsors & Collaborators

• NICHD Global Network for Women's and Children's Health: lead
• RTI International: collaborator
• University of North Carolina, Chapel Hill: collaborator
• Kinshasa School of Public Health: collaborator
• Institute of Nutrition of Central America and Panama (INCAP): collaborator
• Lata Medical Research Foundation, Nagpur: collaborator
• Aga Khan University: collaborator
• University Teaching Hospital, Lusaka, Zambia: collaborator
• KLE Academy of Higher Education and Research (Deemed- to- be-University), Jawaharlal Nehru Medical College (JNMC), Belagavi, India: collaborator
• Bill and Melinda Gates Foundation: collaborator
• University of Virginia: collaborator
• University of Alabama at Birmingham: collaborator
• Thomas Jefferson University: collaborator
• Columbia University: collaborator
• University of Colorado, Denver: collaborator
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator

Study Sites (7)

ICDDR,B

Saidpur, Bangladesh

Location

Kinshasa School of Public Health

Kinshasa, Democratic Republic of the Congo

Location

Institute of Nutrition of Central America And Panama (INCAP)

Chimaltenango, Guatemala

Location

KLE University's J N Medical College

Belagavi, India

Location

Lata Medical Research Foundation

Nagpur, India

Location

Aga Khan University

Karachi, Pakistan

Location

University Teaching Hospital

Lusaka, Zambia

Location

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain

Interventions

caffeine citrate

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

• Melissa Bauserman, MD, MPH

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• Elizabeth M McClure, PhD

  RTI International

  PRINCIPAL INVESTIGATOR

• Denise C Babineau, PhD

  RTI International

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Danielle Wagner, MPH

CONTACT

+1-919-541-6000; wagner@rti.org

Jennifer J Hemingway-Foday, MPH, MSW

CONTACT

hemingway@rti.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The protocol study team, international principal investigator (iPI), site staff and participants will be masked to the assigned treatment arm. Lab personnel will be masked to the assigned treatment arm until assays for samples collected after randomization are complete.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: 1:1 individually randomized, parallel-arm, double-blind, placebo-controlled trial

Study Record Dates

• First Submitted: January 27, 2025
• First Posted: March 3, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): July 1, 2030
• Last Updated: March 3, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

IN (2); ZA (1); PA (1); BA (1); DE (1); GU (1)