Necrotizing Enterocolitis
Conditions
Keywords
Comparative Effectiveness Trial, Necrotizing Enterocolitis, Premature Infants, Blood Transfusion, Withholding enteral feeds
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.
Interventions
OTHERWithholding 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.
OTHERContinued feeds around transfusion
Continued enteral feeds
Sponsors
IWK Health Centre
Canadian Institutes of Health Research (CIHR)
Imperial College London
Imperial Clinical Trials Unit (ICTU)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
No minimum to 30 Weeks
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NEC Stage II | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severe NEC | 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. |
| Death | From randomization to 40 weeks postmenstrual age | All-cause mortality |
| Late onset sepsis | From randomization to 40 weeks postmenstrual age | Culture positive sepsis, onset after 72 hours of life |
| Number of days with a central venous line in situ | From birth to date of discharge home | Number of days with a central venous line in situ |
| Number of central line associated bloodstream infections | From randomization to 40 weeks postmenstrual age | Number of central line associated bloodstream infections: Positive blood culture confirmed bloodstream infection |
| Duration of any parenteral nutrition in days | From birth to 40 weeks postmenstrual age | Duration of any parenteral nutrition in days |
| Growth | At date of discharge home | Weight and head circumference z score. |
| Spontaneous Intestinal Perforation | From randomization to 40 weeks postmenstrual age | Histologically or surgically confirmed or recorded in the death certificate. |
| Duration of hospital stay | 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) |
| Bronchopulmonary Dysplasia (BPD)/Chronic Lung Disease | At 36 weeks postmenstrual age | Requiring respiratory support at 36 weeks gestation |
| Retinopathy of prematurity (ROP) | From randomization to 40 weeks postmenstrual age | ROP requiring treatment |
| Severe Brain Injury | At 40 weeks postmenstrual age | Intraventricular haemorrhage (IVH) grade 3 or 4 or cystic periventricular leukomalacia (PVL) |
Countries
Canada, United Kingdom
Contacts
CONTACTCari-Lee Carnell
CONTACTTara Hatfield
PRINCIPAL_INVESTIGATORBalpreet Singh, MD
IWK Health, Canada
PRINCIPAL_INVESTIGATORJon Dorling, MD
Princess Anne Hospital, UK
PRINCIPAL_INVESTIGATORChris Gale, MD
Imperial College London, UK
Outcome results
None listed