WithHolding Enteral Feeds Around Blood Transfusion (International) (WHEAT)

April 21, 2026 updated by: Dr. Balpreet Singh, IWK Health Centre

The WHEAT International Trial: WithHolding Enteral Feeds Around Red Cell Transfusion to Prevent Necrotizing Enterocolitis in Preterm Neonates: an International, Multi-centre, Randomized Controlled Trial

The WHEAT International trial is a comparative effectiveness trial exploring whether withholding enteral feeds around the time of blood transfusion in very premature infants (<30 weeks) will reduce the occurrence of Necrotizing Enterocolitis (NEC). Currently both continued feeding and withholding feeding are approved care practices. The current study will randomize infants from Neonatal Intensive Care Units (NICUs) across Canada and the United Kingdom (UK) into one of the two care approaches (withholding or continued feeds) to determine if any significant outcomes are found.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating disease that affects mostly the intestine of premature infants. The wall of the intestine is invaded by bacteria, which cause local infection and inflammation that can ultimately destroy the wall of the bowel (intestine). NEC is among the most potentially devastating neonatal diseases and has a mortality of up to 33%, the most severe form (requiring surgery or resulting in death) affects about 5% of infants born at less than 30 gestational weeks; survivors are at high risk of long-term health and developmental problems. Prevention of NEC has been identified as one of the most important research uncertainties in the field of preterm birth. A temporal association between red cell transfusion and the subsequent development of the disease is well described. This 'transfusion-associated NEC' may also be more severe with higher mortality. Very preterm or extremely low birth weight infants are among the most frequently transfused patients: between 56% and 90-95% have at least one transfusion, and those transfused received an average of 5 transfusions in their neonatal stay. Withholding milk feeds during red cell transfusion may reduce the risk of NEC by decreasing postprandial mesenteric ischemia but there may be harmful effects of pausing enteral feeds. However, due to a lack of good quality evidence, there is no consensus regarding the optimal feeding strategy during a blood transfusion.

Both comparator pathways of care are standard practice in Canada and the UK; the WHEAT trial is a comparative effectiveness trial. The two care pathways that will be compared are:

  1. Withholding Feeds Around Transfusion: All enteral feeds will be discontinued (the infant will be placed nil by mouth) for 4 hours prior to packed red cell transfusion, during the packed red cell transfusion and until 4 hours post packed red cell transfusion.
  2. Continuing Feeds Around Transfusion: Enteral feeds will continue to be given prior, during and after the packed red cell transfusion, in the manner in which they were being given prior to the decision to transfuse.

Infants will remain allocated to the same care pathway until 34(+6) weeks(+days) gestational age.

Study Type

Interventional

Enrollment (Estimated)

4333

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3K 6R8
  • United Kingdom
      • Ashford, United Kingdom
        • Recruiting
        • East Kent University Hospitals NHS Foundation Trust (William Harvey Hospital)
        • Contact:
      • Aylesbury, United Kingdom
        • Recruiting
        • Buckinghamshire Healthcare NHS Trust (Stoke Mandeville Hospital)
        • Contact:
      • Barnsley, United Kingdom
        • Recruiting
        • Barnsley Hospital NHS Foundation Trust
        • Contact:
      • Birmingham, United Kingdom
        • Recruiting
        • Birmingham Women's and Children's NHS Foundation Trust (Birmingham Women's Hospital NICU)
        • Contact:
      • Birmingham, United Kingdom
        • Recruiting
        • University Hospitals Birmingham NHS Trust (2 Hospitals: Heartland's Hospital & Good Hope Hospital)
        • Contact:
      • Bradford, United Kingdom
        • Recruiting
        • Bradford Teaching Hospitals NHS Foundation Trust (Bradford Royal Infirmary)
        • Contact:
      • Bristol, United Kingdom
      • Colchester, United Kingdom
      • Coventry, United Kingdom
        • Recruiting
        • University Hospital Coventry & Warwickshire NHS Trust (University Hospital Coventry)
        • Contact:
      • Derby, United Kingdom
        • Recruiting
        • University Hospitals of Derby and Burton NHS Trust (Royal Derby Hospital)
        • Contact:
      • Dundee, United Kingdom
      • Gillingham, United Kingdom
        • Recruiting
        • Medway Hospital NHS Foundation Trust (Oliver Fisher Neonatal Unit, Medway Maritime Hospital)
        • Contact:
      • Gloucester, United Kingdom
        • Recruiting
        • Gloucestershire Hospitals NHS Foundation Trust (Gloucestershire Royal Hospital)
        • Contact:
      • Halifax, United Kingdom
        • Recruiting
        • Calderdale & Huddersfield NHS Foundation Trust (Calderdale Royal Hospital)
        • Contact:
      • Ipswich, United Kingdom
        • Recruiting
        • East and North Essex NHS Foundation Trust - Ipswich Hospital
        • Contact:
      • Leeds, United Kingdom
        • Recruiting
        • Leeds Teaching Hospitals NHS Trust (Leeds General Infirmary & St James' University Hospital)
        • Contact:
      • Leicester, United Kingdom
        • Recruiting
        • University Hospitals of Leicester NHS Trust (Leicester Royal Infirmary)
        • Contact:
      • Liverpool, United Kingdom
        • Recruiting
        • Liverpool Women's Hospital NHS Foundation Trust (Liverpool Women's Hospital)
        • Contact:
      • London, United Kingdom
        • Recruiting
        • North West London NHS Trust (Northwick Park Hospital)
        • Contact:
      • Manchester, United Kingdom
        • Recruiting
        • Manchester University NHS Foundation Trust (2 Hospitals: St Mary's Hospital - Oxford Road, North Manchester General)
        • Contact:
      • Manchester, United Kingdom
        • Recruiting
        • Manchester University NHS Foundation Trust (Wythenshawe)
        • Contact:
      • Newcastle upon Tyne, United Kingdom
        • Recruiting
        • The Newcastle Upon Tyne Hospitals NHS Foundation Trust (Royal Victoria Infirmary)
        • Contact:
      • Nottingham, United Kingdom
        • Recruiting
        • Nottingham University Hospitals NHS Trust (2 Hospitals: City Hospital, Queen's Medical Centre)
        • Contact:
      • Oxford, United Kingdom
        • Recruiting
        • Oxford University Hospitals NHS FT (John Radcliffe Hospital)
        • Contact:
      • Peterborough, United Kingdom
        • Recruiting
        • North West Anglia NHS Trust (Peterborough City Hospital)
        • Contact:
      • Portsmouth, United Kingdom
        • Recruiting
        • Portsmouth University Hospitals NHS Trust (Queen Alexandra Hospital)
        • Contact:
      • Preston, United Kingdom
        • Recruiting
        • Lancashire Teaching Hospitals NHS Foundation Trust (Royal Preston Hospital)
        • Contact:
      • Shrewsbury, United Kingdom
        • Recruiting
        • The Shrewsbury & Telford Hospitals NHS Trust (Royal Shrewsbury Hospital)
        • Contact:
          • Sanjeev Deshpandar, MD
      • Southampton, United Kingdom
        • Recruiting
        • University Hospital Southampton NHS Foundation Trust (Southampton General Hospital)
        • Contact:
      • Wales, United Kingdom
        • Recruiting
        • Betsi Cadwaladr University Health Board (Glan Cwyd Hospital)
        • Contact:
      • Walsall, United Kingdom
        • Recruiting
        • Walsall Healthcare NHS Trust (Walsall Manor Hospital)
        • Contact:
      • Watford, United Kingdom
        • Recruiting
        • West Hertfordshire Hospitals NHS Trust (Watford General Hospital)
        • Contact:
      • Wolverhampton, United Kingdom
        • Recruiting
        • Royal Wolverhampton NHS Trust (New Cross Hospital)
        • Contact:
    • England
      • Norwich, England, United Kingdom
        • Recruiting
        • Norfolk & Norwich University Hospitals NHS Foundation Trust (Norfolk & Norwich University Hospital)
        • Contact:
    • UK
      • Hillingdon, UK, United Kingdom
        • Recruiting
        • The Hillingdon Hospitals NHS Foundation Trust (Hillingdon Hospital)
        • Contact:
      • London, UK, United Kingdom
        • Recruiting
        • Barts Health NHS Trust (3 Hospitals: Royal London Hospital, Whipps Cross Hospital, Newham General Hospital)
        • Contact:
      • London, UK, United Kingdom
        • Recruiting
        • Chelsea and Westminster Hospital NHS Foundation Trust (Chelsea and Westminster Hospital)
        • Contact:
      • London, UK, United Kingdom
        • Recruiting
        • Imperial College Healthcare NHS Trust (2 Hospitals: St Mary's Hospital & Queen Charlotte's and Chelsea Hospital)
        • Contact:
      • Luton, UK, United Kingdom
        • Recruiting
        • Bedfordshire Hospitals NHS Foundation Trust (Luton & Dunstable University Hospital)
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 6 months (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

1. Preterm birth at <30+0 gestational weeks + days

Exclusion Criteria:

  1. Parent(s) opt-out of trial participation.
  2. Packed red cell transfusion with concurrent enteral feeds prior to enrolment. (Infants who have received a packed red cell transfusion while nil-by-mouth are eligible; or minimal enteral nutrition (<15 ml/kg/day feeds) at the time of transfusion; defined as before, during and for at least 4 hours after transfusion, are eligible.
  3. Infants who are not being fed at the time of randomization (<15ml/kg) or where enteral feeding is contraindicated [e.g. Major congenital abnormality of the gastrointestinal tract (GIT)].
  4. Previous episode of NEC Bell stage 2 or higher or SIP prior to first study packed cell transfusion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Withholding feeds around transfusion
All enteral feeds will be discontinued (the infant will be placed nil by mouth) for 4 hours prior to packed red cell transfusion, during the transfusion and until 4 hours post transfusion. During this period, hydration and blood glucose will be maintained according to local practice, commonly by providing parenteral nutrition or intravenous dextrose. Four hours after the red cell transfusion has finished, feeds will be recommenced to how they were being received prior to the decision to transfuse. This duration of withholding feeds will follow the approach used in other trials and observational studies, and identified as the most acceptable in a survey of UK neonatal units. It gives time for milk in the small bowel to transit into the large bowel before the transfusion and for the circulation to stabilize after the transfusion before milk feeds given into the stomach pass through into the small intestine.
Other: Withholding feeds around transfusion
Withholding enteral feeds for preterm infants (<30 weeks) around the time of blood transfusions to determine if any impact on the development and/or severity of Necrotizing Enterocolitis.
Active Comparator: Continuing feeds around transfusion
Enteral feeds will continue to be given prior, during and after the packed red cell transfusion, in the manner in which they were being given prior to the decision to transfuse. Infants will remain allocated to the same care pathway until 34(+6) weeks(+days) gestational age.
Other: Continued feeds around transfusion
Continued enteral feeds

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
NEC Stage II
Time Frame: From randomization to 40 weeks postmenstrual age
Stage II or greater NEC recorded after the first trial blood transfusion; defined according to the modified Bell staging criteria: based on clinical features and abdominal imaging findings, or on surgical or histological findings of NEC.
From randomization to 40 weeks postmenstrual age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severe NEC
Time Frame: From randomization to 40 weeks postmenstrual age
Histologically or surgically confirmed or recorded on the death certificate. These infants will be identified as described in Battersby et al. which will include infants recorded as being transferred for surgery.
From randomization to 40 weeks postmenstrual age
Death
Time Frame: From randomization to 40 weeks postmenstrual age
All-cause mortality
From randomization to 40 weeks postmenstrual age
Late onset sepsis
Time Frame: From randomization to 40 weeks postmenstrual age
Culture positive sepsis, onset after 72 hours of life
From randomization to 40 weeks postmenstrual age
Number of days with a central venous line in situ
Time Frame: From birth to date of discharge home
Number of days with a central venous line in situ
From birth to date of discharge home
Duration of any parenteral nutrition in days
Time Frame: From birth to 40 weeks postmenstrual age
Duration of any parenteral nutrition in days
From birth to 40 weeks postmenstrual age
Growth
Time Frame: At date of discharge home
Weight and head circumference z score.
At date of discharge home
Spontaneous Intestinal Perforation
Time Frame: From randomization to 40 weeks postmenstrual age
Histologically or surgically confirmed or recorded in the death certificate.
From randomization to 40 weeks postmenstrual age
Duration of hospital stay
Time Frame: From birth to date of discharge home
Total duration of neonatal care in days including all levels of care (intensive care, high dependency care, special care and ordinary care)
From birth to date of discharge home
Bronchopulmonary Dysplasia (BPD)/Chronic Lung Disease
Time Frame: At 36 weeks postmenstrual age
Requiring respiratory support at 36 weeks gestation
At 36 weeks postmenstrual age
Retinopathy of prematurity (ROP)
Time Frame: From randomization to 40 weeks postmenstrual age
ROP requiring treatment
From randomization to 40 weeks postmenstrual age
Severe Brain Injury
Time Frame: At 40 weeks postmenstrual age
Intraventricular haemorrhage (IVH) grade 3 or 4 or cystic periventricular leukomalacia (PVL)
At 40 weeks postmenstrual age
Number of central line associated bloodstream infections
Time Frame: From randomization to 40 weeks postmenstrual age
Number of central line associated bloodstream infections: Positive blood culture confirmed bloodstream infection
From randomization to 40 weeks postmenstrual age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IWK Health Centre

Collaborators

Canadian Institutes of Health Research (CIHR)
Imperial College London
Imperial Clinical Trials Unit (ICTU)

Investigators

  • Principal Investigator: Balpreet Singh, MD, IWK Health, Canada
  • Principal Investigator: Jon Dorling, MD, Princess Anne Hospital, UK
  • Principal Investigator: Chris Gale, MD, Imperial College London, UK

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 28, 2022

Primary Completion (Estimated)

March 31, 2027

Study Completion (Estimated)

March 31, 2027

Study Registration Dates

First Submitted

December 8, 2021

First Submitted That Met QC Criteria

January 17, 2022

First Posted (Actual)

January 28, 2022

Study Record Updates

Last Update Posted (Actual)

April 24, 2026

Last Update Submitted That Met QC Criteria

April 21, 2026

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1027137
  • 1025465 (Other Grant/Funding Number: Canadian Institutes of Health Research)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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