Effect of Early Hydrocortisone on Risk of Gastrointestinal Perforations in Extremely Preterm Infants

NCT06515405 | Active Not Recruiting

• 1 other identifier: 293603
• Study Type: observational
• Target: 16,000
• Locations: 1 country
• Sites: 1

Brief Summary

A large, randomised control trial, the PREMILOC trial, has established that giving low dose hydrocortisone prophylactically in the first ten days of life reduces the risk of bronchopulmonary dysplasia in babies born before 32 weeks' gestation. However, the PREMILOC trial was underpowered to investigate rarer side effects, such as gastrointestinal perforation. This study aims to establish whether the odds of gastrointestinal perforation increase when extremely preterm infants are given prophylactic hydrocortisone in the first ten days of life. This retrospective cohort study will use routinely collected data from the U.K. National Neonatal Research Database. The investigators will examine the records of all infants born before 28 weeks' gestation and cared for in English and Welsh neonatal units between 2016 and 2023. Infants will be considered exposed if they received hydrocortisone for at least eight consecutive days, beginning on postnatal day 1 or 2. The primary outcome will be gastrointestinal perforation, as recorded in the infant's neonatal unit record. This outcome will be validated with the original care teams for a sample of babies. Data will be analysed using a propensity score matched approach to reduce the impact of confounding.

Conditions

Intestinal Perforation

Keywords

Preterm Infant; Hydrocortisone

Outcome Measures

Primary Outcomes (1)

• Gastrointestinal (GI) perforation

  A baby will be considered to have had a gastrointestinal perforation if their National Neonatal Research Database record includes a record of a GI perforation in the diagnoses field.

  From date of birth until day 14 of life

Secondary Outcomes (6)

• Survival without gastrointestinal perforation

  From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months

• Mortality before discharge home

  From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months

• Total length of stay

  From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months

• Proportion of days on unit being mechanically ventilated

  From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months

• Bronchopulmonary dysplasia

  From date of birth until 36 weeks' postmenstrual age (PMA)

Other Outcomes (6)

• Necrotising enterocolitis

  From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months

• Severe necrotising enterocolitis

  From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months

• Pragmatically defined necrotising enterocolitis

  From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months

Study Arms (2)

Not exposed to early hydrocortisone

Drug: Hydrocortisone

Exposed to early hydrocortisone

Drug: Hydrocortisone

Interventions

Hydrocortisone DRUG

Cohort members will be considered to be exposed to early hydrocortisone if either: 1. They receive early hydrocortisone started on postnatal day 1 or 2 and given for more than seven consecutive days OR 2. They receive early hydrocortisone started on postnatal day 1 or 2 and are being cared for in a PROHYDRO unit but die on or before postnatal day 8. PROHYDRO units are defined as units who, at the time the baby was born, had implemented a protocol for use of prophylactic hydrocortisone as part of routine care for babies born less than 28 weeks' gestation. A unit may change from being a non-PROHYDRO unit to a PROHYDRO unit if a new early hydrocortisone protocol is introduced during the study period (2016-2023).

Exposed to early hydrocortisone; Not exposed to early hydrocortisone

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Infants born before 28 weeks' gestation and admitted to English and Welsh neonatal units.

You may qualify if:

• Infants who:
• were admitted to a neonatal unit between the 1st January 2016 and 31st March 2023 and
• received any of their care in a NHS neonatal unit in England and Wales (part of UK Neonatal Collaborative and therefore contributing data to the NNRD) and
• were born before 28 weeks' gestation.

You may not qualify if:

• They have missing data for principal background variables (gestational age at birth, birth weight, year of birth and date of death for those that died).
• Their recorded birthweight absolute value z score exceeds 4 or is missing.
• They died on postnatal day 1 or 2 .

Sponsors & Collaborators

• Imperial College London: lead
• Guy's and St Thomas' NHS Foundation Trust: collaborator

Study Sites (1)

Imperial College

London, SW10 9NH, United Kingdom

Location

MeSH Terms

Conditions

Intestinal Perforation; Premature Birth

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2024
• First Posted: July 23, 2024
• Study Start: July 30, 2024
• Primary Completion: December 30, 2024
• Study Completion: August 30, 2025
• Last Updated: October 3, 2024

Record last verified: 2024-10

Locations

GB (1)