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Extreme PrematurityPhase 2SPINNCT06572917

Single-dose Prophylactic INdomethacin in Extremely Preterm Infants

A Phase 2 study testing Indomethacin in people with Extreme Prematurity and Intraventricular Hemorrhage, run by University of British Columbia at 15 sites in 3 countries.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 0 to 12 hours
What is being tested?
Indomethacin
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
500 participants
Where
15 sitesin 3 countries
Study dates
1 Nov 2025to 31 Mar 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 0 to 12 hours
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

15 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Souvik Mitra, MD, PhD contact

6048752000

souvik.mitra@cw.bc.ca

15 sites in 3 countries

Canada8 sites
  • Foothills Medical Center & Alberta Children's Hospital

    Calgary, Alberta

    Hussein Zein, MD, hussein.zein@albertahealthservices.ca

    Khorshid Mohammad, MD, MSc

  • Royal Alexandra Hospital

    Edmonton, Alberta

    Georg Schmolzer, MD, PhD, georg.schmoelzer@me.com

  • IWK Health

    Halifax, Nova Scotia

  • Montreal Children's Hospital

    Montreal, Quebec

    Marc Beltempo, MD, MSc, marc.beltempo@mcgill.ca

  • Royal Columbian Hospital

    New Westminster, British Columbia

    Miroslav Stavel, MD, miroslav.stavel@fraserhealth.ca

  • CHU de Quebec

    Québec, Quebec

    Audrey Hebert, MD, audrey.hebert.2@ulaval.ca

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario

  • BC Women's Hospital

    Vancouver, British Columbia, V6H 3N1

    Souvik Mitra, MD, PhD, 6048752000, souvik.mitra@cw.bc.ca

Other trials in Canada

United States5 sites
  • Texas Health Harris Methodist Hospital Fort Worth

    Fort Worth, Texas, 76104

    Ziad Alhassen, MD, ziad.alhassen@pediatrix.com

    817-250-2000

  • Welcome to Baylor Scott & White Health

    Fort Worth, Texas, 76104

    Ziad Alhassen, MD, 817-926-2544, ziad.alhassen@pediatrix.com

  • University of Pittsburgh School of Medicine

    Pittsburgh, Pennsylvania, 15224-1334

    Toby Yanowitz, MD, MS, yanotd@upmc.edu

  • Kaiser Roseville

    Roseville, California, 95661

    Shayna Gaman-Bean, MD, shayna.k.gaman-bean@kp.org

  • UC Davis Health

    Sacramento, California, 95817

    Steven McElroy, MD, sjmcelroy@ucdavis.edu

Other trials in United States

Australia2 sites
  • Mercy Hospital for Women

    Melbourne, Victoria

  • Monash Children's Hospital

    Melbourne, Victoria

    Calum Roberts, MBChB PhD, calum.roberts@monash.edu

Other trials in Australia

About this study

Official title: Single-dose Prophylactic INdomethacin in Extremely Preterm Infants - A Multicenter Randomized Blinded Placebo-Controlled Trial (the SPIN RCT)

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.

Read the detailed description

BACKGROUND \& IMPORTANCE In Canada, about 900 infants are born extremely preterm at <26 weeks of gestation (GA); nearly four out of 10 of them do not survive or develop severe intraventricular hemorrhage (sIVH). Existing evidence shows that a 3-dose regimen of prophylactic intravenous indomethacin (0.1mg/kg/dose every 24h for 3 doses most commonly used clinically) results in a significant reduction in sIVH, an outcome deemed critical by families. However, use of the conventional 3-dose regimen has declined among clinicians due to perceived adverse effects on the gut, presumed lack of long-term neurodevelopmental benefit and preclusion of other early therapeutic interventions such as ibuprofen or hydrocortisone due to potential increased risk of gut perforation with concomitant use with indomethacin.

Recent pharmacokinetic studies show that indomethacin drug clearance is significantly reduced in infants born ≤26 weeks GA in the first week of life due to their developmental immaturity; and consequently a single 0.1 mg/kg dose likely maintains therapeutic levels for at least 72h - the most critical period of sIVH onset in these smallest infants. However, no RCTs have yet been conducted to establish effectiveness and safety of this single dose regimen in this highest risk population.

GOAL(S) / RESEARCH AIMS Primary goal: To determine the effectiveness and safety of single dose prophylactic indomethacin to prevent morbidity and mortality in extremely preterm infants born <26 weeks GA.

The investigators hypothesize that in preterm infants born <26 weeks GA, when compared to placebo, a single 0.1 mg/kg dose of intravenous indomethacin given prophylactically within the first 12 hours of birth will improve survival without sIVH.

METHODS/APPROACHES/EXPERTISE Study design: Multicenter, blinded, placebo-controlled, individually randomized, Bayesian design RCT Population: Preterm infants born <26 weeks GA and/or <750 g birth weight Intervention: Prophylactic indomethacin: Single-dose intravenous indomethacin (0.1 mg/kg) given within 12 hours of birth. Comparison: Equal volume saline placebo.

Sample size and analysis: The proposed sample size is 500 neonates (250 per arm). The primary analysis will utilize a Bayesian approach using an informative prior that assumes a 5% expected net benefit (in absolute risk difference) with an uncertainty of 5%, with regards to the primary outcome. The trial will be considered successful if it shows that the posterior probability of a positive net benefit is at least 90%.

Setting: Neonatal intensive care units across Canada, the United States and Australia over 3 years. The study will be conducted in 2 phases: (i) an internal pilot phase that will enroll 104 infants born <26 weeks or <750 g birth weight over a period of 1 year; (ii) 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 infants born <26 weeks or <750 g birth weight over a period of 3 years. The total of 500 infants will include the 104 infants enrolled in the first phase of the study.

Primary outcome: Survival without sIVH (grades 3 and 4) at hospital discharge Secondary outcomes include in-hospital clinical outcomes; white matter injury on MRI at term corrected age; neurodevelopmental impairment at 24 (±6) months; pharmacokinetic (PK) profile of single-dose indomethacin; total hospital costs and costs per sIVH or death averted.

EXPECTED OUTCOMES This will be the first RCT to explore the effectiveness and safety of single dose prophylactic indomethacin exclusively in infants born <26 weeks GA who are at the highest risk of severe IVH and death. Apart from the primary and secondary clinical outcomes, this trial will describe the PK profile of single dose indomethacin to establish the ideal therapeutic window for sIVH prevention as well as ascertain the value for money of this therapy in preventing death and sIVH in infants born <26 weeks GA.

Being tested
Indomethacin, Placebo
Keywords
extremely preterm, severe intraventricular hemorrhage, mortality, prophylactic indomethacin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IndomethacinDrug

    Also called Indocid

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

  • PlaceboDrug

    Also called Normal saline

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

Study groups in NCT06572917
Study groupRoleWhat they receive
Single-dose prophylactic indomethacin - SPINExperimentalInfants 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.
Receives: Drug: Indomethacin
ControlPlacebo comparatorEqual volume saline placebo administered intravenously over 20 mins
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

Secondary outcomes (17)
  1. Mortality

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

  2. Severe IVH

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

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

  3. Gastrointestinal perforation

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

  4. Necrotizing enterocolitis (NEC)

    Bell Stage ≥stage 2

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

  5. Acute kidney injury (AKI)

    Defined as ≥stage 1 according to the Neonatal AKI KDIGO classification)

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

  6. Persistent patent ductus arteriosus

    Defined as presence of PDA status on day 7 echocardiogram

    Measured: 7 days postnatal age

  7. Procedural PDA closure

    Definitive PDA closure either by surgical ligation or interventional percutaneous catheter based closure

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

  8. Chronic pulmonary hypertension

    Echocardiographic evidence of chronic pulmonary hypertension

    Measured: birth through 36 weeks' postmenstrual age (PMA)

  9. Grade 3 Bronchopulmonary dysplasia (BPD)

    Defined as need for invasive mechanical ventilation at 36 weeks' postmenstrual age

    Measured: birth through 36 weeks' postmenstrual age (PMA)

  10. Pulmonary hemorrhage

    Defined as blood stained respiratory secretions with an acute significant increase in respiratory requirements (Mean Airway Pressure>12 cm H2O and/or Fraction of inspired O2>60%

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

  11. Duration of invasive mechanical ventilation in days

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

  12. Postnatal corticosteroid use

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

  13. IVH (any grade)

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

  14. Periventricular leukomalacia (any grade)

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

  15. White matter injury (WMI)

    Defined on MRI brain as discrete areas of abnormal white matter T1 hyperintensity in the absence of marked T2 hypo-intensity, or by low-intensity T1 foci

    Measured: Term corrected age (approximately 20 weeks postnatal age)

  16. Severe retinopathy of prematurity (ROP)

    Defined as ROP ≥stage 3

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

  17. Major neurodevelopmental impairment

    Defined as any one of: (i) CP with an inability to walk unassisted; (ii) major developmental delay involving cognition or language or (iii) visual (cannot fixate/legally blind, or corrected acuity <6/60 in both eyes), or hearing impairment (requiring a hearing aid or cochlear implants)

    Measured: 24 (±6) months postmenstrual age (PMA)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Aug 2024
  2. Study start1 Nov 2025 (estimated)
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Mar 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
500 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06572917
Sponsor's protocol ID
H24-02525
Acronym
SPIN
Status last verified
Aug 2025
First submitted
19 Aug 2024
Last updated
3 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All of the individual participant data on clinical outcomes collected during the trial will be shared after deidentification.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Indomethacin in people with Extreme Prematurity and Intraventricular Hemorrhage, run by University of British Columbia at 15 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 3 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Canada, United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Souvik Mitra, MD, PhD (6048752000, souvik.mitra@cw.bc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Survival without severe intraventricular hemorrhage (sIVH) (time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2025; AzTrials last refreshed its copy on 31 Oct 2026.

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