Clinical trial NCT05213806: WithHolding Enteral Feeds Around Blood Transfusion (International)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Necrotizing Enterocolitis
Keywords: Comparative Effectiveness Trial
Necrotizing Enterocolitis
Premature Infants
Blood Transfusion
Withholding enteral feeds
Lead sponsor: IWK Health Centre
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Imperial College London
First posted: 2022-01-28
Enrollment: 4333
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The WHEAT trial is a pragmatic, randomized, controlled, unblinded, international, multicentre, parallel-group superiority trial comparing two clinical care pathways.
Primary purpose: OTHER

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.

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.

Eligibility criteria: 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; buccal colostrum will not be counted as enteral feeding).
3. Infants where enteral feeding is contraindicated in the first 7 days after birth \[e.g. Major congenital abnormality of the gastrointestinal tract (GIT)\].
4. Previous episode of NEC or spontaneous intestinal perforation (SIP) prior to first packed cell transfusion.

Primary outcomes:
measure: NEC Stage II
timeFrame: From randomization to 40 weeks postmenstrual age
Secondary outcomes:
measure: Severe NEC
timeFrame: From randomization to 40 weeks postmenstrual age
measure: Death
timeFrame: From randomization to 40 weeks postmenstrual age
measure: Late onset sepsis
timeFrame: From randomization to 40 weeks postmenstrual age
measure: Number of days with a central venous line in situ
timeFrame: From birth to date of discharge home
measure: Number of central line associated bloodstream infections
timeFrame: From randomization to 40 weeks postmenstrual age
measure: Duration of any parenteral nutrition in days
timeFrame: From birth to 40 weeks postmenstrual age
measure: Growth
timeFrame: At date of discharge home
measure: Spontaneous Intestinal Perforation
timeFrame: From randomization to 40 weeks postmenstrual age
measure: Duration of hospital stay
timeFrame: From birth to date of discharge home
measure: Bronchopulmonary Dysplasia (BPD)/Chronic Lung Disease
timeFrame: At 36 weeks postmenstrual age
measure: Retinopathy of prematurity (ROP)
timeFrame: From randomization to 40 weeks postmenstrual age
measure: Severe Brain Injury
timeFrame: At 40 weeks postmenstrual age
Other outcomes:
Locations:
city: Halifax
country: Canada
facility: IWK Health
state: Nova Scotia
Study officials:
affiliation: IWK Health, Canada
name: Balpreet Singh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Anne Hospital, UK
name: Jon Dorling, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London, UK
name: Chris Gale, MD
role: PRINCIPAL_INVESTIGATOR
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