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NCT Number: NCT06515405

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

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

Sex eligibility

All sexes

Study type

Observational

Primary location

Imperial College

London, SW10 9NH, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.

Exclusion criteria

  • 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 .

Treatment and study plan

Hydrocortisone

Drug

Cohort members will be considered to be exposed to early hydrocortisone if either:

  • They receive early hydrocortisone started on postnatal day 1 or 2 and given for more than seven consecutive days OR
  • 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).

Primary outcomes

  1. Gastrointestinal (GI) perforation

    Time frame: From date of birth until day 14 of life

    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.

Secondary outcomes

  1. Survival without gastrointestinal perforation

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

    Baby survived to discharge from neonatal unit without a gastrointestinal perforation

  2. Mortality before discharge home

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

    Baby died before discharge from neonatal unit

  3. Total length of stay

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

    Length of stay in neonatal care

  4. Proportion of days on unit being mechanically ventilated

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

  5. Bronchopulmonary dysplasia

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

    any respiratory or ventilatory support or supplemental oxygen at 36 weeks' postmenstrual age (PMA)

  6. Bronchopulmonary dysplasia

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

    Using an adapted Jensen criteria based on the highest level of respiratory support at 36 weeks PMA

Other outcomes

  1. Necrotising enterocolitis

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

    UK National Neonatal Audit Programme definition

  2. Severe necrotising enterocolitis

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

    Necrotising enterocolitis confirmed at surgery or post-mortem or stated as cause of death

  3. Pragmatically defined necrotising enterocolitis

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

    a recorded diagnosis of necrotising enterocolitis and received at least 5 consecutive days of antibiotics whilst also nil by mouth

  4. Late onset sepsis

    Time frame: From postnatal day 3 until the date of discharge from final neonatal unit, assessed up to 24 months

    One or more episodes of a positive blood or cerebrospinal fluid culture with either a pure or mixed growth of a known pathogenic organism after the first three days following birth

  5. Brain injury occurring at or soon after birth

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

    Intracranial haemorrhage, perinatal stroke, central nervous system infection, kernicterus (bilirubin encephalopathy), periventricular leukomalacia or any recorded seizure

  6. Treated retinopathy of prematurity

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

    Cryotherapy, laser therapy or injection of anti-vascular endothelial growth factor therapy for ROP in either or both eyes

Sponsors and collaborators

Lead sponsor

Imperial College London

Other

Collaborators

  • Guy's and St Thomas' NHS Foundation Trust

Registry information

Official study title

Effect of Early Hydrocortisone on Risk of Gastrointestinal Perforations in Extremely Preterm Infants: A Protocol for a Retrospective Cohort Study Using Routinely Collected Data

Important dates

Study start
2024
Primary completion
2024
Study completion
2025
First posted
Jul 23, 2024
Registry last updated
Oct 3, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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