Ignite Creation Date:
2024-10-26 @ 3:38 PM
Last Modification Date:
2024-10-26 @ 3:38 PM
Study NCT ID:
NCT06572917
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-19
Brief Title:
Single-dose Prophylactic INdomethacin in Extremely Preterm Infants
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Single-dose Prophylactic INdomethacin in Extremely Preterm Infants - A Multicenter Randomized Blinded Placebo-Controlled Trial the SPIN RCT
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SPIN
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 childs 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 childs 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 ones expectations or biases can influence the results
The investigators will conduct the study in multiple NICUs across Canada the United States and Australia and will enroll 500 babies born 26 weeks or 750 g birth weight over a period of 3 years 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
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 ones expectations or biases can influence the results
The investigators will conduct the study in multiple NICUs across Canada the United States and Australia and will enroll 500 babies born 26 weeks or 750 g birth weight over a period of 3 years 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
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 01mgkgdose 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 01 mgkg 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
GOALS 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 01 mgkg dose of intravenous indomethacin given prophylactically within the first 12 hours of birth will improve survival without sIVH
METHODSAPPROACHESEXPERTISE Study design Multicenter blinded placebo-controlled individually randomized Bayesian design RCT Population Preterm infants born 26 weeks GA andor 750 g birth weight Intervention Prophylactic indomethacin Single-dose intravenous indomethacin 01 mgkg 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 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
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 01 mgkg 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
GOALS 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 01 mgkg dose of intravenous indomethacin given prophylactically within the first 12 hours of birth will improve survival without sIVH
METHODSAPPROACHESEXPERTISE Study design Multicenter blinded placebo-controlled individually randomized Bayesian design RCT Population Preterm infants born 26 weeks GA andor 750 g birth weight Intervention Prophylactic indomethacin Single-dose intravenous indomethacin 01 mgkg 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 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None