Treating Oesophageal Atresia to prevent STricture (TOAST)

BACKGROUND: Babies born with oesophageal atresia (OA) are unable to feed unless they have a surgical intervention to join the two ends of the oesophagus. Following surgery, some surgeons prescribe prophylactic antacid medication believing that this will reduce the incidence of anastomotic stricture. There is no evidence to support this practice, indeed some evidence suggests it may be harmful.

RESEARCH QUESTION: In infants born with oesophageal atresia (Population), does the routine use of antacid medication (Intervention) compared to matched placebo (Comparator) impact the incidence or severity of anastomotic stricture (Outcome)? AIMS AND OBJECTIVES:

(1) To undertake a mixed-methods feasibility study with clinicians and parents to explore acceptability of the proposed trial including aspects of trial design, care pathways and outcomes

(2) Incorporating lessons learnt from the feasibility study, to subsequently undertake a multicentre pragmatic blinded randomised controlled trial (RCT) with internal pilot and integrated economic evaluation

TARGET POPULATION: Newborn infants with oesophageal atresia and distal tracheo-oesophageal fistula undergoing surgical repair. SETTING: Specialist NHS Neonatal Surgical Units in the UK.

HEALTH TECHNOLOGY BEING ASSESSED: Infants enrolled will received either routine antacid medication or placebo from day of surgical repair for one year.

MEASUREMENT OF COSTS AND OUTCOMES: The principal outcome measure of the feasibility phase will be acceptability of the trial protocol to parents and clinicians. Primary outcome for the RCT will be severity of stricture, defined as number of dilatations performed within 1-year of trial entry. Secondary outcomes (measured at timepoints up to 1-year) include incidence of stricture, and other directly related procedures, adverse events, presence of symptoms of gastro-oesophageal reflux, need for treatment of reflux, growth, oral intake, respiratory symptoms, episodes of infection, maternal quality of life and mortality.

Integrated within the trial we will conduct an economic evaluation from an NHS and societal perspective.

SAMPLE SIZE: 211 infants for the RCT would have 90% power to detect an increase of at least 2.7 in the odds of reducing the number of dilatations per infant within 1-year of trial entry by one at 5% two-sided level of statistical significance.

PROJECT TIMETABLES AND RECRUITMENT RATE: Total duration 128 months from 01/03/2021 to 31/10/2031. Feasibility study (9 months). Trial delivery set up (41 months accounting for pause). Planned recruitment start date: 01/05/2025. Total planned recruitment period: 60 months (including an 18 month pilot, with 12 months follow-up, followed by final analysis and dissemination (6 months)).

EXPERTISE IN TEAM: The team has extensive experience in the design and conduct of RCTs in surgery and in newborn infants, trial methodology, surgical expertise, statistical and health economic analysis, qualitative methods, feasibility studies involving children. The study is supported by a specialist perinatal CTU and has strong PPI involvement. Indeed, PPI have suggested the choice of primary outcome and perceive the study as a potential milestone in care of oesophageal atresia patients.

IMPACT AND DISSEMINATION: This trial will provide conclusive evidence concerning the efficacy of antacid medication at reducing incidence and severity of stricture following oesophageal atresia repair. We will disseminate via scientific and lay channels to maximise impact.