WithHolding Enteral Feeds Around Blood Transfusion (International)

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое 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.
• Другое Continued feeds around transfusion
  Continued enteral feeds

Первичные конечные точки

• NEC Stage II [Срок оценки: From randomization to 40 weeks postmenstrual age]

Вторичные конечные точки (12)

• Severe NEC [Срок оценки: From randomization to 40 weeks postmenstrual age]
• Death [Срок оценки: From randomization to 40 weeks postmenstrual age]
• Late onset sepsis [Срок оценки: From randomization to 40 weeks postmenstrual age]
• Number of days with a central venous line in situ [Срок оценки: From birth to date of discharge home]
• Number of central line associated bloodstream infections [Срок оценки: From randomization to 40 weeks postmenstrual age]
• Duration of any parenteral nutrition in days [Срок оценки: From birth to 40 weeks postmenstrual age]
• Growth [Срок оценки: At date of discharge home]
• Spontaneous Intestinal Perforation [Срок оценки: From randomization to 40 weeks postmenstrual age]
• Duration of hospital stay [Срок оценки: From birth to date of discharge home]
• Bronchopulmonary Dysplasia (BPD)/Chronic Lung Disease [Срок оценки: At 36 weeks postmenstrual age]
• Retinopathy of prematurity (ROP) [Срок оценки: From randomization to 40 weeks postmenstrual age]
• Severe Brain Injury [Срок оценки: At 40 weeks postmenstrual age]

Критерии участия

Критерии включения

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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Великобритания · 39 центров

• Norfolk & Norwich University Hospitals NHS Foundation Trust (Norfolk & Norwich University — Norwich
• The Hillingdon Hospitals NHS Foundation Trust (Hillingdon Hospital) — Hillingdon
• Barts Health NHS Trust (3 Hospitals: Royal London Hospital, Whipps Cross Hospital, Newham — London
• Chelsea and Westminster Hospital NHS Foundation Trust (Chelsea and Westminster Hospital) — London
• Imperial College Healthcare NHS Trust (2 Hospitals: St Mary's Hospital & Queen Charlotte's — London
• Bedfordshire Hospitals NHS Foundation Trust (Luton & Dunstable University Hospital) — Luton
• East Kent University Hospitals NHS Foundation Trust (William Harvey Hospital) — Ashford
• Buckinghamshire Healthcare NHS Trust (Stoke Mandeville Hospital) — Aylesbury
• … и ещё 31 центр

Канада · 1 центр

• IWK Health — Halifax

Публикации

• 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 N PMID 28404014
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT05213806 · 1027137 · 1025465

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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