Single-dose Prophylactic INdomethacin in Extremely Preterm Infants

Summary

In Canada, about 900 babies each year are born very early (\<26 weeks of gestation) and have a high chance of dying or having a serious bleed in the brain. Families of these extremely preterm babies consider preventing severe brain bleeding as critical to their child's health and well-being. A medicine called indomethacin, when given intravenously in 3-doses, is known to reduce severe brain bleeding. But use of this drug is variable among clinicians working in the neonatal intensive care unit (NICU) due to (a) its side effects on the gut; (b) possible harm when used with other medications; (c) a notion that despite reducing brain bleeds, the child's long-term brain development is not improved. Emerging evidence suggests that a single low-dose indomethacin regimen may be equally effective in reducing severe brain bleeding as compared to a traditional 3-dose regimen.

The investigators propose a blinded randomized controlled trial, a study design where babies born \<26 weeks will be randomly assigned within 12 hours of birth to either a single dose of intravenous indomethacin or similar looking placebo in the form a saline solution. The study will test if a single dose indomethacin regimen is effective in improving survival of these babies without the devastating complication of severe brain bleeding. In this study the care providers and researchers will be unaware as to which baby receives indomethacin and which baby receives placebo to ensure no one's expectations or biases can influence the results.

The investigators will conduct the study in multiple NICUs across Canada, the United States and Australia in 2 phases: First, an internal pilot phase that will enroll 104 babies born \<26 weeks or \<750 g birth weight over a period of 1 year. If the investigators are successful in achieving their target enrolment in the pilot phase, they will move on to the second phase and continue enrollment up to a total of 500 babies born \<26 weeks or \<750 g birth weight over a period of 3 years. The total of 500 babies will include the 104 babies enrolled in the first phase of the study. This study will help the investigators determine in the most unbiased way whether a single dose of indomethacin given immediately after birth in the smallest babies born \<26 weeks of gestation can safely and effectively reduce severe brain bleeding.

Conditions

• Extreme Prematurity
• Intraventricular Hemorrhage
• Morbidity;Newborn

Interventions

DRUG

Indomethacin

Single dose of 0.1 mg/kg dose intravenous indomethacin as a slow infusion over 20 mins

DRUG

Placebo

Single dose of intravenous normal saline placebo as a slow infusion over 20 mins

Sponsors & Collaborators

• University of British Columbia

  lead OTHER

Principal Investigators

• Souvik Mitra, MD, PhD · University of British Columbia

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

0 Hours

Max Age

12 Hours

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-11-01

Primary Completion

2028-12-31

Completion

2031-03-31

FDA Drug

Yes

Countries

• United States
• Australia
• Canada

Study Locations