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Appendectomy versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial
  1. Nigel J Hall1,
  2. Simon Eaton2,
  3. Olivier Abbo3,
  4. Alexis P Arnaud4,
  5. Marianne Beaudin5,
  6. Mary Brindle6,
  7. Andreana Bütter7,
  8. Dafydd Davies8,
  9. Tim Jancelewicz9,
  10. Kathy Johnson10,
  11. Richard Keijzer11,
  12. Eveline Lapidus-Krol12,
  13. Martin Offringa13,
  14. Nelson Piché5,
  15. Risto Rintala14,
  16. Erik Skarsgard15,
  17. Jan F Svensson16,
  18. Wendy J Ungar13,
  19. Tomas Wester16,
  20. Andrew R Willan17,
  21. Augusto Zani12,
  22. Shawn D St Peter10,
  23. Agostino Pierro12
  1. 1 University Surgery Unit, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK
  2. 2 Developmental Biology & Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK
  3. 3 Pediatric Surgery Department, Hôpital des Enfants, Centre Hospitalier Universitaire Toulouse, Toulouse, France
  4. 4 Paediatric Surgery Department, Hôpital Sud, Centre Hospitalier Universitaire, Rennes, France
  5. 5 Division of PediatricSurgery, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada
  6. 6 Departments of Surgery and Community Health Sciences, Alberta Children's Hospital, Calgary, Alberta, Canada
  7. 7 Division of Pediatric Surgery, Children’s Hospital,London Health Sciences Centre, London, Ontario, Canada
  8. 8 Department of General and Thoracic Surgery, IWK Health Centre, Halifax, Nova Scotia, Canada
  9. 9 Division of Pediatric Surgery, Le Bonheur Children's Hospital, University of Tennessee Health Science Center, Memphis, Tennessee, USA
  10. 10 Department of Surgery, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA
  11. 11 Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada
  12. 12 Division of Thoracic and General Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
  13. 13 Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario, Canada
  14. 14 Department of Pediatric Surgery, Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
  15. 15 Department of Surgery, BC Children's Hospital, Vancouver, British Columbia, Canada
  16. 16 Department of Pediatric Surgery, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
  17. 17 Ontario Child Health Support Unit, SickKids Research Institute, Toronto, Ontario, Canada
  1. Correspondence to Nigel J Hall; n.j.hall{at}soton.ac.uk

Abstract

Background Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of non-operative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed.

Methods Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5–16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis will be randomised (1:1 ratio) to receive either laparoscopic appendectomy or treatment with intravenous (minimum 12 hours) followed by oral antibiotics (total course 10 days). Allocation to groups will be stratified by gender, duration of symptoms (> or <48 hours) and centre. Children in both treatment groups will follow a standardised treatment pathway. Primary outcome is treatment failure defined as additional intervention related to appendicitis requiring general anaesthesia within 1 year of randomisation (including recurrent appendicitis) or negative appendectomy. Important secondary outcomes will be reported and a cost-effectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin. Planned sample size is 978 children.

Discussion The APPY trial will be the first multicentre randomised trial comparing non-operative treatment with appendectomy for acute uncomplicated appendicitis in children. The results of this trial have the potential to revolutionise the treatment of this common gastrointestinal emergency. The randomised design will limit the effect of bias on outcomes seen in other studies.

Trial registration number clinicaltrials.gov: NCT02687464. Registered on Jan 13th 2016.

  • Paediatric Surgery
  • Gastroenterology
  • Evidence Based Medicine

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors All authors have contributed to study design and writing of the protocol. This manuscript was drafted by NJH with help from SE. The draft was revised by ES, SDSP, AP, WJU and ARW. All authors have seen and approved the final version of the manuscript.

  • Competing interests None declared.

  • Ethics approval The study has received ethical approval in the following centres: Children's Mercy Hospital, Kansas City, Missouri, USA; BC Children's Hospital, Vancouver, British Columbia, Canada; Children's Hospital of Western Ontario, London, Ontario, Canada; Children’s Hospital Winnipeg, Winnipeg, Mannitoba, Canada; Karolinska University Hospital, Stockholm, Sweden; Hospital for Children and Adolescents, University of Helsinki, Finland. The study is undergoing ethical review in the remaining centres.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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