Single-dose Prophylactic INdomethacin in Extremely Preterm Infants

NCT06572917 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: H24-02525
• Study Type: interventional
• Target: 500
• Locations: 3 countries
• Sites: 15

Brief 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

Keywords

extremely preterm; severe intraventricular hemorrhage; mortality; prophylactic indomethacin

Outcome Measures

Primary Outcomes (1)

• Survival without severe intraventricular hemorrhage (sIVH)

  Any IVH more than grade 2 (i.e., grade 3, grade 4/intraparenchymal hemorrhage/perventricular hemorrhagic infarction is classified as sIVH

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

Secondary Outcomes (17)

• Mortality

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

• Severe IVH

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

• Gastrointestinal perforation

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

• Necrotizing enterocolitis (NEC)

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

• Acute kidney injury (AKI)

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

Other Outcomes (4)

• Pharmacokinetic outcomes

  7 days postnatal age

• Health Economic outcomes

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

• Primary feasibility outcomes (during the internal pilot)

  Through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

Study Arms (2)

Single-dose prophylactic indomethacin - SPIN

EXPERIMENTAL

Infants randomized to the SPIN group will receive a single 0.1 mg/kg dose of intravenous indomethacin within 12h of birth as a slow infusion over 20 mins.

Drug: Indomethacin

Control

PLACEBO COMPARATOR

Equal volume saline placebo administered intravenously over 20 mins

Drug: Placebo

Interventions

Indomethacin DRUG

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

Also known as: Indocid

Single-dose prophylactic indomethacin - SPIN

Placebo DRUG

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

Also known as: Normal saline

Control

Eligibility Criteria

• Age: 0 Hours - 12 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Extremely preterm infants born \<26 completed weeks of GA and/or extremely low BW infants born \<750g

You may not qualify if:

• antenatal diagnosis of duct dependent CHD
• acute hypoxic respiratory failure \[defined as fraction of inspired oxygen (FiO2)\>0.60 for ≥2h)
• inhaled nitric oxide (iNO) therapy due to suspected or confirmed acute pulmonary hypertension (PH)
• receipt of prophylactic or therapeutic hydrocortisone
• antenatal diagnosis of renal anomalies
• initial platelet count \<50x109/L
• decision to withhold/withdraw life-sustaining treatments

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (15)

Kaiser Roseville

Roseville, California, 95661, United States

Location

UC Davis Health

Sacramento, California, 95817, United States

Location

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, 15224-1334, United States

Location

Texas Health Harris Methodist Hospital Fort Worth

Fort Worth, Texas, 76104, United States

Location

Welcome to Baylor Scott & White Health

Fort Worth, Texas, 76104, United States

Location

Mercy Hospital for Women

Melbourne, Victoria, Australia

Location

Monash Children's Hospital

Melbourne, Victoria, Australia

Location

Foothills Medical Center & Alberta Children's Hospital

Calgary, Alberta, Canada

Location

Royal Alexandra Hospital

Edmonton, Alberta, Canada

Location

Royal Columbian Hospital

New Westminster, British Columbia, Canada

Location

BC Women's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

Location

IWK Health

Halifax, Nova Scotia, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

Montreal Children's Hospital

Montreal, Quebec, Canada

Location

CHU de Quebec

Québec, Quebec, Canada

Location

MeSH Terms

Interventions

Indomethacin; Saline Solution

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Souvik Mitra, MD, PhD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Souvik Mitra, MD, PhD

CONTACT

6048752000; souvik.mitra@cw.bc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The indomethacin and placebo will be provided to the bedside nurse as per allocation using pre-filled syringes masked with a yellow tape (as reconstituted indomethacin has a slightly yellow tinge). All members of the medical team and outcome assessors will remain blinded to the allocation throughout the trial duration.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 19, 2024
• First Posted: August 27, 2024
• Study Start: November 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): March 31, 2031
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: As soon as possible, wherever legally and ethically possible. In addition, data from the trial will be made available upon reasonable request.

Locations

US (5); CA (8); AU (2)