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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 4,333
- 试验地点
- 40
- 主要终点
- NEC Stage II
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- — 至 30 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Preterm birth at <30+0 gestational weeks + days
排除标准
- •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.
研究组 & 干预措施
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 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.
干预措施: Withholding feeds around transfusion (Other)
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.
干预措施: Continued feeds around transfusion (Other)
结局指标
主要结局
NEC Stage II
时间窗: 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.
次要结局
- 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)
- Death(From randomization to 40 weeks postmenstrual age)
- Growth(At date of discharge home)
- Severe NEC(From randomization to 40 weeks postmenstrual age)
- Duration of any parenteral nutrition in days(From birth to 40 weeks postmenstrual age)
- Spontaneous Intestinal Perforation(From randomization to 40 weeks postmenstrual age)
- Late onset sepsis(From randomization to 40 weeks postmenstrual age)
- Retinopathy of prematurity (ROP)(From randomization to 40 weeks postmenstrual age)
- Duration of hospital stay(From birth to date of discharge home)
- Severe Brain Injury(At 40 weeks postmenstrual age)
- Bronchopulmonary Dysplasia (BPD)/Chronic Lung Disease(At 36 weeks postmenstrual age)
研究者
Dr. Balpreet Singh
Principal Investigator
IWK Health Centre