Condition category
Nutritional, Metabolic, Endocrine
Date applied
20/07/2017
Date assigned
24/07/2017
Last edited
24/07/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Every year about 1200 babies in England, Wales and Scotland suffer from a lack of oxygen around birth which can lead to long-term brain injury or death. This is called Hypoxic Ischaemic Encephalopathy (HIE). Research has shown that cooling babies with HIE by a few degrees for the first 3 days protects the brain therefore all babies with moderate or severe HIE in the UK are treated with therapeutic hypothermia (cooling). Doctors do not know how best to care for babies while they are cooled. A key question is “how to provide nutrition to babies during cooling”. There are two main parts to this question, milk feeds (“enteral” nutrition) and intravenous nutrition (“parenteral” nutrition). - Some neonatal units in the UK carefully feed babies (usually with maternal breast milk) while they are cooled. This avoids intravenous lines and is believed to help them feed and go home earlier. Other neonatal units do not feed cooled babies because they worry about a condition called necrotising enterocolitis (a devastating and often fatal disease that causes inflammation of the digestive system) which might be more common with feeding. All cooled babies need intravenous fluid (even when milk feeds are given it takes several days before enough fluid can be given this way). Some neonatal units give babies intravenous nutrition (which contains fat, protein, carbohydrate, vitamins and minerals) as this may improve growth and recovery. Other neonatal units only give intravenous dextrose with simple salts because of concerns that intravenous nutrition leads to more infections. It is not known how best to provide either milk or intravenous nutrition to cooled babies. This study compares these different ways of providing nutrition using a research database called the National Neonatal Research Database (NNRD). In England, Scotland and Wales doctors and nurses looking after babies in neonatal care (including all cooled babies) use an Electronic Health Record system. Data from this system are anonymised (no baby can be identified) and form the NNRD, so the NNRD holds data from all babies who have been looked after on NHS neonatal units. This has been developed closely with parents and charities. The aim of this study is to determine the best enteral and parenteral nutrition strategy for newborns with HIR during and after therapeutic hypothermia.

Who can participate?
Infants born at 36 gestational weeks or later who received therapeutic hypothermia for at least 72 hours

What does the study involve?
This study collects data in the NNRD about babies and their nutrition during therapeutic hypothermia. Babies who were fed milk while cooled are compared to those who were not fed any milk by collecting rates of necrotising enterocolitis. Babies who get intravenous nutrition are compared to those who get intravenous dextrose. The rate of infection, the amount of babies who died, how long they stayed in neonatal care, how soon they were able to breastfeed and how many who were breastfeed when they go home is collected from the NNRD. This is done to find the optimum nutrition strategy for newborns.

What are the possible benefits and risks of participating?
There are no direct benefits or risks with participating.

Where is the study run from?
This study is taking place at the Chelsea and Westminster Hospital (UK) and includes data from 200 NHS neonatal units in England, Scotland and Wales (UK).

When is the study starting and how long is it expected to run for?
September 2016 to January 2019

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
1. Mr Richard Colquhoun
ndau@imperial.ac.uk
2. Dr Chris Gale
christopher.gale@imperial.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Mr Richard Colquhoun

ORCID ID

Contact details

Neonatal Data Analysis Unit
Section of Neonatal Medicine
Imperial College London
Chelsea and Westminster Hospital Campus
369 Fulham Road
London
SW10 9NH
United Kingdom
+44 203 315 5841
ndau@imperial.ac.uk

Type

Scientific

Additional contact

Dr Chris Gale

ORCID ID

http://orcid.org/0000-0003-0707-876X

Contact details

Section of Neonatal Medicine
Imperial College London
Chelsea and Westminster Hospital Campus
369 Fulham Road
London
SW10 9NH
United Kingdom
+44 203 315 3519
christopher.gale@imperial.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

17IC4064

Study information

Scientific title

Optimising newborn nutrition during therapeutic hypothermia: An observational study using routinely collected data

Acronym

Study hypothesis

The overarching aim of this project is to determine the optimum enteral and parenteral nutrition strategy for newborns with Hypoxic Ischaemic Encephalopathy (HIE) during and after therapeutic hypothermia. To do this we will perform two primary comparisons:

Enteral: To determine whether any enteral (milk) feeding, when compared to withholding enteral feeding (no milk), during therapeutic hypothermia, is associated with a difference in the incidence of necrotising enterocolitis.
Parenteral: To determine whether provision of intravenous dextrose, when compared to provision of parenteral nutrition, during therapeutic hypothermia, is associated with a difference in the incidence of blood stream infection.

Ethics approval

East Midlands-Leicester Central Research Ethics Commitee, ref: 17/EM/0307

Study design

Retrospective cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

There is no participant information sheet for this study

Condition

Hypoxic-ischaemic encephalopathy requiring therapeutic hypothermia

Intervention

This study collects existing data help in the National Neonatal Research Database (NNRD). The analysis will apply the potential outcomes framework using propensity score matching. The data was collected from January 2008 to December 2016.

All analysis uses anonymised data held in an approved research database, the NNRD. No patient identifiable information is used in this study.

The data is collected in order to compare the milk feeding and intravenous nutrition that babies receive during therapeutic hypothermia.

Milk feeding: Data is collected about babies who are fed milk while cooled with those that are not fed any milk. This is to establish whether there is any difference in rates of necrotising enterocolitis.

Intravenous Nutrition: Data is collected to compare babies who get intravenous nutrition with those that only get intravenous dextrose. The main data collected is the rate of infection. The amount of babies who die, how long they stay in neonatal care, how soon breastfeeding starts and many are breastfed when they go home is also collected.

De-identified data held in the NNRD and the potential outcomes framework with application of propensity scoring is used to define matched subgroups for comparison.

Intervention type

Mixed

Phase

Drug names

Primary outcome measures

1. Necrotising enterocolitis is defined using the case definition (Battersby et al 2017) between birth and final neonatal unit discharge, and is collected and analysed using the data from the NNRD
2. Blood stream infection defined as pure growth of a recognised pathogen from a normally sterile site between birth and final neonatal unit discharge, and is collected and analysed using the data NNRD

Secondary outcome measures

1. Survival is measured using the NNRD data between birth and neonatal unit discharge
2. Length of stay is measured using the number of days between first neonatal unit admission and final neonatal unit discharge for surviving infants using the NNRD data between birth and final neonatal unit discharge
3. Breastfeeding at discharge is measured using any breastfeeding using NNRD discharge at time of final neonatal unit discharge
4. Hypoglycaemia is measured as any diagnosis of hypoglycaemia recorded during therapeutic hypothermia and is collected and analysed using the data from the NNRD
5. Time to full feed is measured as the number of days until an infant is recorded as not requiring any parenteral nutrition or intravenous fluid between birth and final neonatal unit discharge and is collected and analysed using the data from the NNRD
6. Growth, weight and head circumference for post-menstrual age standard deviation score at final neonatal unit discharge is measured using the data from the NNRD at final neonatal unit discharge

Overall trial start date

15/09/2016

Overall trial end date

09/01/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Infants born at 36 gestational weeks or later
3. Received therapeutic hypothermia for Hypoxic Ischaemic Encephalopathy (HIE) for at least 72 hours
3. Died during therapeutic hypothermia

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

We estimate that the National Neonatal Research Database (NNRD) holds data on approximately 7200 eligible infants

Participant exclusion criteria

Infants with missing data for principal background and outcome variables. Missing values for other variables will be dealt with using multiple imputation.

Recruitment start date

01/10/2017

Recruitment end date

01/10/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Chelsea and Westminster NHS Foundation Trust
369 Fulham Road
London
SW10 9NH
United Kingdom

Sponsor information

Organisation

Imperial College London

Sponsor details

215
2nd Floor
Medical School Building
Norfolk Place
St Mary's Campus
London
W2 1PG
United Kingdom
+44 20 7594 9459
becky.ward@imperial.ac.uk

Sponsor type

University/education

Website

www.imperial.ac.uk

Funders

Funder type

Not defined

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Final study report and academic publication
• This will describe the work undertaken, research, conclusions and recommendations from both parent and health professional perspectives
• The parent perspective will be publicised through social media, websites and other materials to highlight the value of such involvement

Scientific presentations
• These will be at neonatal and perinatal conferences and will describe clinical outcomes of different nutritional strategies
• We plan for parent and/or patient co-applicants to deliver presentations at these meetings to highlight the value of such involvement

Scientific publications
• Clinical results will be published in peer reviewed neonatal/paediatric journals to maximise impact within the UK and internationally

Social media
• Personal, charity and research group Twitter, Facebook and related social media resources will link to scientific publications and plain English summaries (produced by parent and parent representative co-applicants)

Websites
• Charity (Bliss) and professional (United Kingdom Neonatal Collaborative: UKNC, Imperial College London and University of Nottingham) websites will publicise the results of this work and highlight the value added by parent involvement

Professional communications
• UKNC and University of Nottingham newsletters and other communications will publicise results and link to scientific publications

IPD sharing statement:
The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository called the National Neonatal Research Database (NNRD) http://www.imperial.ac.uk/neonatal-data-analysis-unit/neonatal-data/utilising-the-nnrd/
The data stored here will be de-identified paraticipant level data that is updated quarterly. All parents are informed and have the opportunity to opt out of their baby's data from being included in the NNRD. To access the database, ethical as well as other approvals are required, which is outlined here: http://www.imperial.ac.uk/neonatal-data-analysis-unit/neonatal-data/utilising-the-nnrd/

Intention to publish date

01/03/2019

Participant level data

Stored in repository

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes