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

NCT ID: NCT06515405

Last Updated: 2024-10-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 16000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-07-30
• Study Completion Date: 2025-08-30

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Not exposed to early hydrocortisone

Hydrocortisone

Intervention Type: 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

Hydrocortisone

Intervention Type: 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).

Interventions

Hydrocortisone

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).

Intervention Type: DRUG

Eligibility Criteria

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 .

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guy's and St Thomas' NHS Foundation Trust

OTHER

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Imperial College

London, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

293603

Identifier Type: -

Identifier Source: org_study_id