Necrotizing EnterocolitisWHEATNCT05213806
WithHolding Enteral Feeds Around Blood Transfusion (International)
A study testing Withholding feeds around transfusion and Continued feeds around transfusion in people with Necrotizing Enterocolitis, run by IWK Health Centre at 40 sites in 2 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages Up to 30 weeks
- Conditions the study is for
- Necrotizing Enterocolitis
- What is being tested?
- Withholding feeds around transfusion and Continued feeds around transfusion
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4,333 participants
- Where
- 40 sitesin 2 countries
- Study dates
- 28 Jan 2022to 31 Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 30 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 1. Preterm birth at <30+0 gestational weeks + days
Who cannot join
- Parent(s) opt-out of trial participation.
- 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.
- 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)].
- Previous episode of NEC Bell stage 2 or higher or SIP prior to first study packed cell transfusion.
Trial locations and contacts
40 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
40 sites in 2 countries
United Kingdom39 sites, 39 recruiting
- Recruiting
East Kent University Hospitals NHS Foundation Trust (William Harvey Hospital)
Ashford
Sean Mun, MD, kwokseanmun@nhs.net
- Recruiting
Buckinghamshire Healthcare NHS Trust (Stoke Mandeville Hospital)
Aylesbury
Gopa Sarkar, gopa.sarkar@nhs.net
- Recruiting
Barnsley Hospital NHS Foundation Trust
Barnsley
Ezzedin Gouta, MD, egouta@nhs.net
- Recruiting
Birmingham Women's and Children's NHS Foundation Trust (Birmingham Women's Hospital NICU)
Birmingham
Gemma Holder, MD, gemma.holder@nhs.net
- Recruiting
University Hospitals Birmingham NHS Trust (2 Hospitals: Heartland's Hospital & Good Hope Hospital)
Birmingham
Imogen Storey, MD, imogen.storey@uhb.nhs.uk
- Recruiting
Bradford Teaching Hospitals NHS Foundation Trust (Bradford Royal Infirmary)
Bradford
Sam Oddie, MD, sam.oddie@bthft.nhs.uk
- Recruiting
North Bristol NHS Trust (Southmead Hospital)
Bristol
Daniela Vieten-Kay, MD, daniela.vieten-kay@nbt.nhs.uk
- Recruiting
East and North Essex NHS Foundation Trust - Colchester Hospital
Colchester
Jonathan Campbell, MD, jonathan.campbell@esneft.nhs.uk
- Recruiting
University Hospital Coventry & Warwickshire NHS Trust (University Hospital Coventry)
Coventry
Arthi Lakshmanan, MD, arthi.lakshmanan@uhcw.nhs.uk
- Recruiting
University Hospitals of Derby and Burton NHS Trust (Royal Derby Hospital)
Derby
Shalini Ojha, PhD, Shalini.Ojha@nottingham.ac.uk
- Recruiting
NHS Tayside (Ninewells Hospital)
Dundee
Jennifer Scotland, MD, jennifer.scotland3@nhs.scot
- Recruiting
Medway Hospital NHS Foundation Trust (Oliver Fisher Neonatal Unit, Medway Maritime Hospital)
Gillingham
Ghada Ramadan, MD, gramadan@nhs.net
- Recruiting
Gloucestershire Hospitals NHS Foundation Trust (Gloucestershire Royal Hospital)
Gloucester
Joanne Colliver, RN, joanne.colliver@nhs.net
- Recruiting
Calderdale & Huddersfield NHS Foundation Trust (Calderdale Royal Hospital)
Halifax
James Houston, MD, james.houston2@cht.nhs.uk
- Recruiting
The Hillingdon Hospitals NHS Foundation Trust (Hillingdon Hospital)
Hillingdon, UK
Elizabeth Lek, MD, elizabeth.lek@nhs.net
- Recruiting
East and North Essex NHS Foundation Trust - Ipswich Hospital
Ipswich
Prathiba Pai, MD, prathiba.pai@esneft.nhs.uk
- Recruiting
Leeds Teaching Hospitals NHS Trust (Leeds General Infirmary & St James' University Hospital)
Leeds
Amelia Shaw, MD, amelia.shaw2@nhs.net
- Recruiting
University Hospitals of Leicester NHS Trust (Leicester Royal Infirmary)
Leicester
Joe Fawke, MD, joe.fawke@uhl-tr.nhs.uk
- Recruiting
Liverpool Women's Hospital NHS Foundation Trust (Liverpool Women's Hospital)
Liverpool
Srinivasarao Babarao, MD, srinivasarao.babarao@lwh.nhs.uk
- Recruiting
Barts Health NHS Trust (3 Hospitals: Royal London Hospital, Whipps Cross Hospital, Newham General Hospital)
London, UK
Ajay Sinja, MD, ajay.sinha@nhs.net
- Recruiting
Chelsea and Westminster Hospital NHS Foundation Trust (Chelsea and Westminster Hospital)
London, UK
Prof Christopher Gale, MD, Christopher.gale2@nhs.net
- Recruiting
Imperial College Healthcare NHS Trust (2 Hospitals: St Mary's Hospital & Queen Charlotte's and Chelsea Hospital)
London, UK
Jayanta Banerjee, MD, jayanta.banerjee@nhs.net
- Recruiting
North West London NHS Trust (Northwick Park Hospital)
London
Richard Nicholl, MD, rnicholl@nhs.net
- Recruiting
Bedfordshire Hospitals NHS Foundation Trust (Luton & Dunstable University Hospital)
Luton, UK
Doris Iyambo, MD, doris.iyambo@ldh.nhs.uk
- Recruiting
Manchester University NHS Foundation Trust (2 Hospitals: St Mary's Hospital - Oxford Road, North Manchester General)
Manchester
Ruth Gottstein, MD, ruth.gottstein@mft.nhs.uk
- Recruiting
Manchester University NHS Foundation Trust (Wythenshawe)
Manchester
Kuldip Bakaya, MD, kuldip.bakaya@mft.nhs.uk
- Recruiting
The Newcastle Upon Tyne Hospitals NHS Foundation Trust (Royal Victoria Infirmary)
Newcastle upon Tyne
Elda Dermyshi, MD, elda.dermyshi@nhs.net
- Recruiting
Norfolk & Norwich University Hospitals NHS Foundation Trust (Norfolk & Norwich University Hospital)
Norwich, England
Jasmine Myhill, rdoffice@nnuh.nhs.uk
- Recruiting
Nottingham University Hospitals NHS Trust (2 Hospitals: City Hospital, Queen's Medical Centre)
Nottingham
Dulip Jayasinghe, MD, dulip.jayasinghe1@nhs.net
- Recruiting
Oxford University Hospitals NHS FT (John Radcliffe Hospital)
Oxford
Eleri Adams, MD, eleri.adams@ouh.nhs.uk
- Recruiting
North West Anglia NHS Trust (Peterborough City Hospital)
Peterborough
Katherine McDevitt, MD, katherine.mcdevitt@nhs.net
- Recruiting
Portsmouth University Hospitals NHS Trust (Queen Alexandra Hospital)
Portsmouth
Tim Scorrer, MD, tim.scorrer@porthosp.nhs.uk
- Recruiting
Lancashire Teaching Hospitals NHS Foundation Trust (Royal Preston Hospital)
Preston
Richa Gupta, MD, richa.gupta@lthtr.nhs.uk
- Recruiting
The Shrewsbury & Telford Hospitals NHS Trust (Royal Shrewsbury Hospital)
Shrewsbury
Sanjeev Deshpandar, MD
- Recruiting
University Hospital Southampton NHS Foundation Trust (Southampton General Hospital)
Southampton
Mark Johnson, MD, mark.johnson@uhs.nhs.uk
- Recruiting
Betsi Cadwaladr University Health Board (Glan Cwyd Hospital)
Wales
Ian Barnard, MD, ian.barnard@wales.nhs.uk
- Recruiting
Walsall Healthcare NHS Trust (Walsall Manor Hospital)
Walsall
Pooja Siddhi, MD, p.siddhi@nhs.net
- Recruiting
West Hertfordshire Hospitals NHS Trust (Watford General Hospital)
Watford
Nazakat Merchant, MD, nazakat.merchant@nhs.net
- Recruiting
Royal Wolverhampton NHS Trust (New Cross Hospital)
Wolverhampton
Richard Heaver, MD, r.heaver@nhs.net
Canada1 site, 1 recruiting
- Recruiting
IWK Health
Halifax, Nova Scotia, B3K 6R8
Cari-Lee Carnell, 9024706630, cari-lee.carnell@iwk.nshealth.ca
Balpreet Singh, MD
About this study
Official title: 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.
Read the 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:
- 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.
- 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.
- Conditions
- Necrotizing Enterocolitis
- Being tested
- Withholding feeds around transfusion, Continued feeds around transfusion
- Keywords
- Comparative Effectiveness Trial, Necrotizing Enterocolitis, Premature Infants, Blood Transfusion, Withholding enteral feeds
- Medical subject headings
- Enterocolitis, Necrotizing, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Withholding feeds around transfusionOther
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.
Continued feeds around transfusionOther
Continued enteral feeds
| Study group | Role | What they receive |
|---|---|---|
| Withholding feeds around transfusion | Active comparator | 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. Receives: Other: Withholding feeds around transfusion |
| Continuing feeds around transfusion | Active comparator | 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. Receives: Other: Continued feeds around transfusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
NEC Stage II
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.
Measured: From randomization to 40 weeks postmenstrual age
Secondary outcomes (12)
Severe NEC
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.
Measured: From randomization to 40 weeks postmenstrual age
Death
All-cause mortality
Measured: From randomization to 40 weeks postmenstrual age
Late onset sepsis
Culture positive sepsis, onset after 72 hours of life
Measured: From randomization to 40 weeks postmenstrual age
Number of days with a central venous line in situ
Number of days with a central venous line in situ
Measured: From birth to date of discharge home
Number of central line associated bloodstream infections
Number of central line associated bloodstream infections: Positive blood culture confirmed bloodstream infection
Measured: From randomization to 40 weeks postmenstrual age
Duration of any parenteral nutrition in days
Duration of any parenteral nutrition in days
Measured: From birth to 40 weeks postmenstrual age
Growth
Weight and head circumference z score.
Measured: At date of discharge home
Spontaneous Intestinal Perforation
Histologically or surgically confirmed or recorded in the death certificate.
Measured: From randomization to 40 weeks postmenstrual age
Duration of hospital stay
Total duration of neonatal care in days including all levels of care (intensive care, high dependency care, special care and ordinary care)
Measured: From birth to date of discharge home
Bronchopulmonary Dysplasia (BPD)/Chronic Lung Disease
Requiring respiratory support at 36 weeks gestation
Measured: At 36 weeks postmenstrual age
Retinopathy of prematurity (ROP)
ROP requiring treatment
Measured: From randomization to 40 weeks postmenstrual age
Severe Brain Injury
Intraventricular haemorrhage (IVH) grade 3 or 4 or cystic periventricular leukomalacia (PVL)
Measured: At 40 weeks postmenstrual age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2022
- Study start28 Jan 2022
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Necrotizing EnterocolitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The WHEAT trial is a randomised controlled, unblinded, international, multicentre, parallel-group superiority trial comparing two clinical pathways. Participants will be randomised to either pathway. In the United Kingdom, the trial is running across 77 neonatal units. In Canada, the trial is running at 15 neonatal sites, all of which participate in recruitment, intervention delivery, and follow-up procedures in line with the study protocol. Across both countries, participant recruitment will continue until 31 December 2026. The last participant randomised is expected to complete the trial participation period by 31 March 2027, following completion of the follow-up period defined as neonatal unit discharge or 40+0 weeks postmenstrual age, whichever occurs first. Analysis of trial data will take place after completion of follow-up, with results anticipated to be communicated by September 2027.
- Masking
- None (open label)
- Enrolment
- 4,333 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IWK Health Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Imperial College London
- Responsible party
- Principal investigator, Dr. Balpreet Singh, IWK Health Centre
- Investigators
- Balpreet Singh, MD, Principal investigator, IWK Health, CanadaJon Dorling, MD, Principal investigator, Princess Anne Hospital, UKChris Gale, MD, Principal investigator, Imperial College London, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05213806
- Sponsor's protocol ID
- 1027137
- Other IDs
- PJT-175289
- Acronym
- WHEAT
- Status last verified
- Nov 2025
- First submitted
- 8 Dec 2021
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified participant data, the data dictionary, statistical code and other study materials.
Publications
Battersby C, Longford N, Mandalia S, Costeloe K, Modi N; UK Neonatal Collaborative Necrotising Enterocolitis (UKNC-NEC) study group. Incidence and enteral feed antecedents of severe neonatal necrotising enterocolitis across neonatal networks in England, 2012-13: a whole-population surveillance study. Lancet Gastroenterol Hepatol. 2017 Jan;2(1):43-51. doi: 10.1016/S2468-1253(16)30117-0. Epub 2016 Nov 8.
PubMed 28404014Duro D, Kalish LA, Johnston P, Jaksic T, McCarthy M, Martin C, Dunn JC, Brandt M, Nobuhara KK, Sylvester KG, Moss RL, Duggan C. Risk factors for intestinal failure in infants with necrotizing enterocolitis: a Glaser Pediatric Research Network study. J Pediatr. 2010 Aug;157(2):203-208.e1. doi: 10.1016/j.jpeds.2010.02.023. Epub 2010 May 6.
PubMed 20447649Hintz SR, Kendrick DE, Stoll BJ, Vohr BR, Fanaroff AA, Donovan EF, Poole WK, Blakely ML, Wright L, Higgins R; NICHD Neonatal Research Network. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics. 2005 Mar;115(3):696-703. doi: 10.1542/peds.2004-0569.
PubMed 15741374Rees CM, Pierro A, Eaton S. Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2007 May;92(3):F193-8. doi: 10.1136/adc.2006.099929. Epub 2006 Sep 19.
PubMed 16984980Duley L, Uhm S, Oliver S; Preterm Birth Priority Setting Partnership Steering Group. Top 15 UK research priorities for preterm birth. Lancet. 2014 Jun 14;383(9934):2041-2042. doi: 10.1016/S0140-6736(14)60989-2. No abstract available.
PubMed 24931684Seges RA, Kenny A, Bird GW, Wingham J, Baals H, Stauffer UG. Pediatric surgical patients with severe anaerobic infection: report of 16 T-antigen positive cases and possible hazards of blood transfusion. J Pediatr Surg. 1981 Dec;16(6):905-10. doi: 10.1016/s0022-3468(81)80844-5.
PubMed 6279816Stritzke AI, Smyth J, Synnes A, Lee SK, Shah PS. Transfusion-associated necrotising enterocolitis in neonates. Arch Dis Child Fetal Neonatal Ed. 2013 Jan;98(1):F10-4. doi: 10.1136/fetalneonatal-2011-301282. Epub 2012 Mar 23.
PubMed 22447991Blau J, Calo JM, Dozor D, Sutton M, Alpan G, La Gamma EF. Transfusion-related acute gut injury: necrotizing enterocolitis in very low birth weight neonates after packed red blood cell transfusion. J Pediatr. 2011 Mar;158(3):403-9. doi: 10.1016/j.jpeds.2010.09.015. Epub 2010 Nov 10.
PubMed 21067771Mally P, Golombek SG, Mishra R, Nigam S, Mohandas K, Depalhma H, LaGamma EF. Association of necrotizing enterocolitis with elective packed red blood cell transfusions in stable, growing, premature neonates. Am J Perinatol. 2006 Nov;23(8):451-8. doi: 10.1055/s-2006-951300. Epub 2006 Sep 28.
PubMed 17009195Cunningham KE, Okolo FC, Baker R, Mollen KP, Good M. Red blood cell transfusion in premature infants leads to worse necrotizing enterocolitis outcomes. J Surg Res. 2017 Jun 1;213:158-165. doi: 10.1016/j.jss.2017.02.029. Epub 2017 Feb 28.
PubMed 28601308Keir AK, Yang J, Harrison A, Pelausa E, Shah PS; Canadian Neonatal Network. Temporal changes in blood product usage in preterm neonates born at less than 30 weeks' gestation in Canada. Transfusion. 2015 Jun;55(6):1340-6. doi: 10.1111/trf.12998. Epub 2015 Feb 5.
PubMed 25652740Kirpalani H, Whyte RK, Andersen C, Asztalos EV, Heddle N, Blajchman MA, Peliowski A, Rios A, LaCorte M, Connelly R, Barrington K, Roberts RS. The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. J Pediatr. 2006 Sep;149(3):301-307. doi: 10.1016/j.jpeds.2006.05.011.
PubMed 16939737Jasani B, Rao S, Patole S. Withholding Feeds and Transfusion-Associated Necrotizing Enterocolitis in Preterm Infants: A Systematic Review. Adv Nutr. 2017 Sep 15;8(5):764-769. doi: 10.3945/an.117.015818. Print 2017 Sep.
PubMed 28916576Sahin S, Gozde Kanmaz Kutman H, Bozkurt O, Yavanoglu Atay F, Emre Canpolat F, Uras N, Suna Oguz S, Underwood MA. Effect of withholding feeds on transfusion-related acute gut injury in preterm infants: a pilot randomized controlled trial. J Matern Fetal Neonatal Med. 2020 Dec;33(24):4139-4144. doi: 10.1080/14767058.2019.1597844. Epub 2019 Mar 28.
PubMed 30890001Neu J. Necrotizing enterocolitis: the search for a unifying pathogenic theory leading to prevention. Pediatr Clin North Am. 1996 Apr;43(2):409-32. doi: 10.1016/s0031-3955(05)70413-2.
PubMed 8614608
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05213806
- Acronym / sponsor ID
- WHEAT / 1027137
- Conditions
- Necrotizing Enterocolitis
- Keywords
- Comparative Effectiveness Trial, Necrotizing Enterocolitis, Premature Infants, Blood Transfusion, Withholding enteral feeds
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 4,333 participants (estimated)
- Lead sponsor
- IWK Health CentreUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Imperial College London
- Study start
- 28 Jan 2022 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 28 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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.
- 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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The WHEAT trial is a randomised controlled, unblinded, international, multicentre, parallel-group superiority trial comparing two clinical pathways. Participants will be randomised to either pathway. In the United Kingdom, the trial is running across 77 neonatal units. In Canada, the trial is running at 15 neonatal sites, all of which participate in recruitment, intervention delivery, and follow-up procedures in line with the study protocol. Across both countries, participant recruitment will continue until 31 December 2026. The last participant randomised is expected to complete the trial participation period by 31 March 2027, following completion of the follow-up period defined as neonatal unit discharge or 40+0 weeks postmenstrual age, whichever occurs first. Analysis of trial data will take place after completion of follow-up, with results anticipated to be communicated by September 2027.
| Arm | Type | Receives |
|---|---|---|
| Withholding feeds around transfusion | Active comparator | Other: Withholding feeds around transfusionAll 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. |
| Continuing feeds around transfusion | Active comparator | Other: Continued feeds around transfusionEnteral 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. |
Who may qualify
- Ages
- Up to 30 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- 1. Preterm birth at <30+0 gestational weeks + days
Key exclusion criteria (4 listed)
- Parent(s) opt-out of trial participation.
- 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.
- 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)].
- Previous episode of NEC Bell stage 2 or higher or SIP prior to first study packed cell transfusion.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Withholding feeds around transfusionWithholding 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. | Other | Withholding feeds around transfusion |
| Continued feeds around transfusionContinued enteral feeds | Other | Continuing feeds around transfusion |
Primary outcome
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.
12 secondary outcomes
Severe NEC
Time frame: From randomization to 40 weeks postmenstrual age
Death
Time frame: From randomization to 40 weeks postmenstrual age
Late onset sepsis
Time frame: 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 central line associated bloodstream infections
Time frame: From randomization to 40 weeks postmenstrual age
Duration of any parenteral nutrition in days
Time frame: From birth to 40 weeks postmenstrual age
Growth
Time frame: At date of discharge home
Spontaneous Intestinal Perforation
Time frame: From randomization to 40 weeks postmenstrual age
Duration of hospital stay
Time frame: From birth to date of discharge home
Bronchopulmonary Dysplasia (BPD)/Chronic Lung Disease
Time frame: At 36 weeks postmenstrual age
Retinopathy of prematurity (ROP)
Time frame: From randomization to 40 weeks postmenstrual age
Severe Brain Injury
Time frame: At 40 weeks postmenstrual age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
- Background: PubMed 28404014Battersby C, Longford N, Mandalia S, Costeloe K, Modi N; UK Neonatal Collaborative Necrotising Enterocolitis (UKNC-NEC) study group. Incidence and enteral feed antecedents of severe neonatal necrotising enterocolitis across neonatal networks in England, 2012-13: a whole-population surveillance study. Lancet Gastroenterol Hepatol. 2017 Jan;2(1):43-51. doi: 10.1016/S2468-1253(16)30117-0. Epub 2016 Nov 8.
- Background: PubMed 20447649Duro D, Kalish LA, Johnston P, Jaksic T, McCarthy M, Martin C, Dunn JC, Brandt M, Nobuhara KK, Sylvester KG, Moss RL, Duggan C. Risk factors for intestinal failure in infants with necrotizing enterocolitis: a Glaser Pediatric Research Network study. J Pediatr. 2010 Aug;157(2):203-208.e1. doi: 10.1016/j.jpeds.2010.02.023. Epub 2010 May 6.
- Background: PubMed 15741374Hintz SR, Kendrick DE, Stoll BJ, Vohr BR, Fanaroff AA, Donovan EF, Poole WK, Blakely ML, Wright L, Higgins R; NICHD Neonatal Research Network. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics. 2005 Mar;115(3):696-703. doi: 10.1542/peds.2004-0569.
- Background: PubMed 16984980Rees CM, Pierro A, Eaton S. Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2007 May;92(3):F193-8. doi: 10.1136/adc.2006.099929. Epub 2006 Sep 19.
- Background: PubMed 24931684Duley L, Uhm S, Oliver S; Preterm Birth Priority Setting Partnership Steering Group. Top 15 UK research priorities for preterm birth. Lancet. 2014 Jun 14;383(9934):2041-2042. doi: 10.1016/S0140-6736(14)60989-2. No abstract available.
- Background: PubMed 6279816Seges RA, Kenny A, Bird GW, Wingham J, Baals H, Stauffer UG. Pediatric surgical patients with severe anaerobic infection: report of 16 T-antigen positive cases and possible hazards of blood transfusion. J Pediatr Surg. 1981 Dec;16(6):905-10. doi: 10.1016/s0022-3468(81)80844-5.
- Background: PubMed 22447991Stritzke AI, Smyth J, Synnes A, Lee SK, Shah PS. Transfusion-associated necrotising enterocolitis in neonates. Arch Dis Child Fetal Neonatal Ed. 2013 Jan;98(1):F10-4. doi: 10.1136/fetalneonatal-2011-301282. Epub 2012 Mar 23.
- Background: PubMed 21067771Blau J, Calo JM, Dozor D, Sutton M, Alpan G, La Gamma EF. Transfusion-related acute gut injury: necrotizing enterocolitis in very low birth weight neonates after packed red blood cell transfusion. J Pediatr. 2011 Mar;158(3):403-9. doi: 10.1016/j.jpeds.2010.09.015. Epub 2010 Nov 10.
- Background: PubMed 17009195Mally P, Golombek SG, Mishra R, Nigam S, Mohandas K, Depalhma H, LaGamma EF. Association of necrotizing enterocolitis with elective packed red blood cell transfusions in stable, growing, premature neonates. Am J Perinatol. 2006 Nov;23(8):451-8. doi: 10.1055/s-2006-951300. Epub 2006 Sep 28.
- Background: PubMed 28601308Cunningham KE, Okolo FC, Baker R, Mollen KP, Good M. Red blood cell transfusion in premature infants leads to worse necrotizing enterocolitis outcomes. J Surg Res. 2017 Jun 1;213:158-165. doi: 10.1016/j.jss.2017.02.029. Epub 2017 Feb 28.
- Background: PubMed 25652740Keir AK, Yang J, Harrison A, Pelausa E, Shah PS; Canadian Neonatal Network. Temporal changes in blood product usage in preterm neonates born at less than 30 weeks' gestation in Canada. Transfusion. 2015 Jun;55(6):1340-6. doi: 10.1111/trf.12998. Epub 2015 Feb 5.
- Background: PubMed 16939737Kirpalani H, Whyte RK, Andersen C, Asztalos EV, Heddle N, Blajchman MA, Peliowski A, Rios A, LaCorte M, Connelly R, Barrington K, Roberts RS. The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. J Pediatr. 2006 Sep;149(3):301-307. doi: 10.1016/j.jpeds.2006.05.011.
- Individual participant dataSharing planned: Yes. De-identified participant data, the data dictionary, statistical code and other study materials.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Balpreet Singh, MD principal investigator
IWK Health, Canada
Jon Dorling, MD principal investigator
Princess Anne Hospital, UK
Chris Gale, MD principal investigator
Imperial College London, UK
40 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Withholding feeds around transfusion and Continued feeds around transfusion in people with Necrotizing Enterocolitis, run by IWK Health Centre at 40 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United Kingdom, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cari-Lee Carnell (9024706630, cari-lee.carnell@iwk.nshealth.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
NEC Stage II (time frame: From randomization to 40 weeks postmenstrual age). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05213806, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026.