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19/85 Anti-reflux medication to reduce stricture formation following oesophageal atresia repair

 

Contents

Introduction

The aim of the HTA Programme is to ensure that high quality research information on the effectiveness, costs and broader impact of health technology is produced in the most efficient way for those who use, manage, provide care in or develop policy for the NHS. Topics for research are identified and prioritised to meet the needs of the NHS. Health technology assessment forms a substantial portfolio of work within the National Institute for Health Research and each year about fifty new studies are commissioned to help answer questions of direct importance to the NHS. The studies include both primary research and evidence synthesis.

Research Question: In infants born with oesophageal atresia, does the routine use of anti-reflux medications reduce the incidence or severity of anastomotic stricture?

  1. Intervention: Anti-reflux medication. Type and duration of anti-reflux medication to be defined and justified by applicants.
  2. Patient group: Infants born with oesophageal atresia who have had atresia repair surgery.
    Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field.
  3. Setting: Secondary care.
  4. Comparator: Placebo.
  5. Study design: 
    (i) A feasibility study to explore the acceptability of the trial to parents, carers and clinicians.
    (ii) A randomised controlled trial including an internal pilot study to determine the ability to recruit and randomise to the trial.
    Clear stop/go criteria should be provided to inform progression from the feasibility study to internal pilot and from internal pilot to full trial.
  6. Important outcomes: Incidence and severity of anastomotic stricture, adverse effects (e.g., infection, mortality), ongoing reflux.
    Other outcomes: Cost effectiveness, quality of life, need for dilatations.
  7. Minimum duration of follow-up: 2 years for the full trial.
    If appropriate, researchers should consider obtaining consent from participants to allow potential future follow up through efficient means (such as routine data) as part of a separately funded study.

Rationale:

Oesophageal atresia is a rare birth defect affecting the tube through which food passes from the mouth to the stomach. In babies with the condition, the upper part of the oesophagus fails to join the lower oesophagus and stomach, meaning food cannot reach the stomach. Oesophageal atresia may be diagnosed before birth, via ultrasound, but usually it is diagnosed within 24 hours of birth due to the baby having problems with breathing and swallowing.

Oesophageal atresia repair is performed urgently once the baby has been stabilised, and can either be done as a primary repair or staged repair depending on the severity of the malformation.

Oesophageal motility problems occur in nearly all children who have had oesophageal atresia repair and are thought to contribute to the subsequent development of gastroesophageal reflux disease in a large number of patients. Reflux is also felt to be a contributing factor in stricture formation following this repair. Dilatations of oesophageal anastomotic strictures have been cited by parents as causing significant morbidity and disruption to life. Anti-reflux treatment (proton pump inhibitors, H2 blockers) may alleviate reflux and reduce stricture formation postoperatively, but may be associated with adverse effects such as gastrointestinal and/or respiratory infections, and potentially sepsis in infants. Despite some observational work, there is no RCT evidence comparing anti-reflux medication with no treatment, yet guidelines recommend prophylactic medication (proton pump inhibitors specifically) following oesophageal atresia repair based on low and very low quality evidence. In the UK and Ireland, half of these repair procedures are followed up with anti-reflux medication, but the remainder are not. Clearly this is an area of uncertainty. The HTA programme would like to commission an RCT to determine if there is a proven benefit to the use of prophylactic anti-reflux medication in these patients.

Additional commissioning brief background information

A background document is available that provides further information to support applicants for this call. It is intended to summarise what prompted the call and the existing evidence base, including relevant work from the HTA and wider NIHR research portfolio. It was researched and written on the basis of information from a search of relevant sources and databases, and in consultation with a number of experts in the field. If you would like a copy please email htaresearchers@nihr.ac.uk.

Making an application

If you wish to submit a Stage 1 application for this call, the online application form can be found on the Funding opportunities page.  To select this call, use the filters on the right of the screen or search using the call name and/or number.

Your application must be submitted on-line no later than 1pm on the 4th December 2019. Applications will be considered by the HTA Funding Committee at its meeting in January.

Guidance notes and supporting information for HTA Programme applications are available by clicking the links.

IMPORTANT: Shortlisted Stage 1 applicants will be given eight weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in May.

Applications received after 1300 hours on the due date will not be considered.

Should you have any queries please contact us:

Email: htacommissioning@nihr.ac.uk

Telephone: Commissioning Funding Committee 02380 595510