WithHolding Enteral Feeds Around Blood Transfusion (International)

NCT05213806 | Recruiting DMC

• 2 other identifiers: 10271371025465
• Study Type: interventional
• Target: 4,333
• Locations: 2 countries
• Sites: 40

Brief 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). 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.

Conditions

Necrotizing Enterocolitis

Keywords

Comparative Effectiveness Trial; Necrotizing Enterocolitis; Premature Infants; Blood Transfusion; Withholding enteral feeds

Outcome Measures

Primary Outcomes (1)

• 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.

  From randomization to 40 weeks postmenstrual age

Secondary Outcomes (12)

• Severe NEC

  From randomization to 40 weeks postmenstrual age

• Death

  From randomization to 40 weeks postmenstrual age

• Late onset sepsis

  From randomization to 40 weeks postmenstrual age

• Number of days with a central venous line in situ

  From birth to date of discharge home

• Number of central line associated bloodstream infections

  From randomization to 40 weeks postmenstrual age

Study Arms (2)

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.

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.

Other: Continued feeds around transfusion

Interventions

Withholding feeds around transfusion OTHER

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.

Withholding feeds around transfusion

Continued feeds around transfusion OTHER

Continued enteral feeds

Continuing feeds around transfusion

Eligibility Criteria

• Age: Up to 30 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \. Preterm birth at \<30+0 gestational weeks + days

You may not qualify if:

• 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.

Sponsors & Collaborators

• IWK Health Centre: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Imperial College London: collaborator
• Imperial Clinical Trials Unit (ICTU): collaborator

Study Sites (40)

IWK Health

Halifax, Nova Scotia, B3K 6R8, Canada

RECRUITING

Norfolk & Norwich University Hospitals NHS Foundation Trust (Norfolk & Norwich University Hospital)

Norwich, England, United Kingdom

RECRUITING

The Hillingdon Hospitals NHS Foundation Trust (Hillingdon Hospital)

Hillingdon, UK, United Kingdom

RECRUITING

Barts Health NHS Trust (3 Hospitals: Royal London Hospital, Whipps Cross Hospital, Newham General Hospital)

London, UK, United Kingdom

RECRUITING

Chelsea and Westminster Hospital NHS Foundation Trust (Chelsea and Westminster Hospital)

London, UK, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust (2 Hospitals: St Mary's Hospital & Queen Charlotte's and Chelsea Hospital)

London, UK, United Kingdom

RECRUITING

Bedfordshire Hospitals NHS Foundation Trust (Luton & Dunstable University Hospital)

Luton, UK, United Kingdom

RECRUITING

East Kent University Hospitals NHS Foundation Trust (William Harvey Hospital)

Ashford, United Kingdom

RECRUITING

Buckinghamshire Healthcare NHS Trust (Stoke Mandeville Hospital)

Aylesbury, United Kingdom

RECRUITING

Barnsley Hospital NHS Foundation Trust

Barnsley, United Kingdom

RECRUITING

Birmingham Women's and Children's NHS Foundation Trust (Birmingham Women's Hospital NICU)

Birmingham, United Kingdom

RECRUITING

University Hospitals Birmingham NHS Trust (2 Hospitals: Heartland's Hospital & Good Hope Hospital)

Birmingham, United Kingdom

RECRUITING

Bradford Teaching Hospitals NHS Foundation Trust (Bradford Royal Infirmary)

Bradford, United Kingdom

RECRUITING

North Bristol NHS Trust (Southmead Hospital)

Bristol, United Kingdom

RECRUITING

East and North Essex NHS Foundation Trust - Colchester Hospital

Colchester, United Kingdom

RECRUITING

University Hospital Coventry & Warwickshire NHS Trust (University Hospital Coventry)

Coventry, United Kingdom

RECRUITING

University Hospitals of Derby and Burton NHS Trust (Royal Derby Hospital)

Derby, United Kingdom

RECRUITING

NHS Tayside (Ninewells Hospital)

Dundee, United Kingdom

RECRUITING

Medway Hospital NHS Foundation Trust (Oliver Fisher Neonatal Unit, Medway Maritime Hospital)

Gillingham, United Kingdom

RECRUITING

Gloucestershire Hospitals NHS Foundation Trust (Gloucestershire Royal Hospital)

Gloucester, United Kingdom

RECRUITING

Calderdale & Huddersfield NHS Foundation Trust (Calderdale Royal Hospital)

Halifax, United Kingdom

RECRUITING

East and North Essex NHS Foundation Trust - Ipswich Hospital

Ipswich, United Kingdom

RECRUITING

Leeds Teaching Hospitals NHS Trust (Leeds General Infirmary & St James' University Hospital)

Leeds, United Kingdom

RECRUITING

University Hospitals of Leicester NHS Trust (Leicester Royal Infirmary)

Leicester, United Kingdom

RECRUITING

Liverpool Women's Hospital NHS Foundation Trust (Liverpool Women's Hospital)

Liverpool, United Kingdom

RECRUITING

North West London NHS Trust (Northwick Park Hospital)

London, United Kingdom

RECRUITING

Manchester University NHS Foundation Trust (2 Hospitals: St Mary's Hospital - Oxford Road, North Manchester General)

Manchester, United Kingdom

RECRUITING

Manchester University NHS Foundation Trust (Wythenshawe)

Manchester, United Kingdom

RECRUITING

The Newcastle Upon Tyne Hospitals NHS Foundation Trust (Royal Victoria Infirmary)

Newcastle upon Tyne, United Kingdom

RECRUITING

Nottingham University Hospitals NHS Trust (2 Hospitals: City Hospital, Queen's Medical Centre)

Nottingham, United Kingdom

RECRUITING

Oxford University Hospitals NHS FT (John Radcliffe Hospital)

Oxford, United Kingdom

RECRUITING

North West Anglia NHS Trust (Peterborough City Hospital)

Peterborough, United Kingdom

RECRUITING

Portsmouth University Hospitals NHS Trust (Queen Alexandra Hospital)

Portsmouth, United Kingdom

RECRUITING

Lancashire Teaching Hospitals NHS Foundation Trust (Royal Preston Hospital)

Preston, United Kingdom

RECRUITING

The Shrewsbury & Telford Hospitals NHS Trust (Royal Shrewsbury Hospital)

Shrewsbury, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust (Southampton General Hospital)

Southampton, United Kingdom

RECRUITING

Betsi Cadwaladr University Health Board (Glan Cwyd Hospital)

Wales, United Kingdom

RECRUITING

Walsall Healthcare NHS Trust (Walsall Manor Hospital)

Walsall, United Kingdom

RECRUITING

West Hertfordshire Hospitals NHS Trust (Watford General Hospital)

Watford, United Kingdom

RECRUITING

Royal Wolverhampton NHS Trust (New Cross Hospital)

Wolverhampton, United Kingdom

RECRUITING

Related Publications (16)

• 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.

  PMID: 28404014 BACKGROUND

• Duro 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.

  PMID: 20447649 BACKGROUND

• Hintz 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.

  PMID: 15741374 BACKGROUND

• Rees 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.

  PMID: 16984980 BACKGROUND

• Duley 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.

  PMID: 24931684 BACKGROUND

• Seges 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.

  PMID: 6279816 BACKGROUND

• Stritzke 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.

  PMID: 22447991 BACKGROUND

• Blau 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.

  PMID: 21067771 BACKGROUND

• Mally 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.

  PMID: 17009195 BACKGROUND

• Cunningham 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.

  PMID: 28601308 BACKGROUND

• Keir 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.

  PMID: 25652740 BACKGROUND

• Kirpalani 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.

  PMID: 16939737 BACKGROUND

• Jasani 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.

  PMID: 28916576 BACKGROUND

• Sahin 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.

  PMID: 30890001 BACKGROUND

• Neu 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.

  PMID: 8614608 BACKGROUND

• Battersby C, Longford N, Costeloe K, Modi N; UK Neonatal Collaborative Necrotising Enterocolitis Study Group. Development of a Gestational Age-Specific Case Definition for Neonatal Necrotizing Enterocolitis. JAMA Pediatr. 2017 Mar 1;171(3):256-263. doi: 10.1001/jamapediatrics.2016.3633.

  PMID: 28046187 BACKGROUND

MeSH Terms

Conditions

Enterocolitis, Necrotizing; Premature Birth

Condition Hierarchy (Ancestors)

Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Balpreet Singh, MD

  IWK Health, Canada

  PRINCIPAL INVESTIGATOR

• Jon Dorling, MD

  Princess Anne Hospital, UK

  PRINCIPAL INVESTIGATOR

• Chris Gale, MD

  Imperial College London, UK

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cari-Lee Carnell

CONTACT

9024706630; cari-lee.carnell@iwk.nshealth.ca

Tara Hatfield

CONTACT

9024706630; tara.hatfield@iwk.nshealth.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: December 8, 2021
• First Posted: January 28, 2022
• Study Start: January 28, 2022
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 24, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); GB (39)