Acute uncomplicated appendicitis study: rationale and protocol for a multicentre, prospective randomised controlled non-inferiority study to evaluate the safety and effectiveness of non-operative management in children with acute uncomplicated appendicitis

Jane Xu, Yingrui Cyril Liu, Susan Adams, Jonathan Karpelowsky, Jane Xu, Yingrui Cyril Liu, Susan Adams, Jonathan Karpelowsky

Abstract

Introduction: This article presents an overview of a prospective randomised controlled non-inferiority study designed to evaluate the safety and effectiveness of non-operative management (NOM) with operative management in children with acute uncomplicated appendicitis (AUA). Here, we present the study protocol for this APRES study, a multicentre Australian study. The rationale and details of future analysis, in particular, non-inferiority calculations, cost-effectiveness, feasibility and acceptability of each intervention.

Design: A multicentre, prospective randomised controlled clinical trial, conducted in 2 Australian tertiary paediatric hospitals.

Participants: Children who meet the inclusion criteria of an age between 5 and 15 years and a clinical diagnosis of AUA will be invited to participate, and after consent will be randomised via a computer-based program into treatment groups. The study started in June 2016, and the target recruitment is 220 patients.

Interventions: Children in the control group will be treated with prophylactic antibiotics and appendicectomy, and those in the intervention group will be treated with antibiotic therapy alone. Primary outcome measures include unplanned or unnecessary operation and complications at 30 days. Secondary outcomes include longer term complications within 1 year, length of stay, time off work and school analgesic requirements and cost.

Analysis: Data analyses will be on the intention-to-treat principle using non-inferiority analysis. Analysis will include the Pearson χ2 test for categorical variables and independent sample t-test or Mann-Whitney test for continuous variables. Non-inferiority for NOM will be tested using 1-sided Wald tests with an α level of 0.05.

Ethics and dissemination: The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospital Network. In addition, results will be reported through academic journals, seminars and conference presentations.

Trial registration numbers: NCT02795793; ACTRN12616000788471.

Keywords: PAEDIATRIC SURGERY.

Conflict of interest statement

Conflicts of Interest: None declared.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Figures

Figure 1
Figure 1
Study design diagram and participant timeline.

References

    1. Wilson BE, Cheney L, Patel B et al. . Appendicectomy at a children's hospital: what has changed over a decade? ANZ J Surg 2012;82:639–43. 10.1111/j.1445-2197.2012.06168.x
    1. McBurney C. Experience with early operative interference in cases of disease of the vermiform appendix by Charles McBurney, M.D., Visiting Surgeon to the Roosevelt Hospital, New York city. Rev Surg 1969;26:153–66.
    1. Esposito C, Calvo AI, Castagnetti M et al. . Open versus laparoscopic appendectomy in the pediatric population: a literature review and analysis of complications. J Laparoendosc Adv Surg Tech A 2012;22:834–9. 10.1089/lap.2011.0492
    1. Wray CJ, Kao LS, Millas SG et al. . Acute appendicitis: controversies in diagnosis and management. Curr Probl Surg 2013;50:54–86. 10.1067/j.cpsurg.2012.10.001
    1. Leung TTW, Dixon E, Gill M et al. . Bowel obstruction following appendectomy. Ann Surg 2009;250:51–3. 10.1097/SLA.0b013e3181ad64a7
    1. Güller U, Rosella L, McCall J et al. . Negative appendicectomy and perforation rates in patients undergoing laparoscopic surgery for suspected appendicitis . Br J Surg 2011;98:589–95. 10.1002/bjs.7395
    1. Flum DR, Morris A, Koepsell T et al. . Has misdiagnosis of appendicitis decreased over time? JAMA 2001;286:1748–53. 10.1001/jama.286.14.1748
    1. St Peter SD, Aguayo P, Frase JD et al. . Initial laparoscopic appendectomy versus initial nonoperative management and interval appendectomy for perforated appendicitis with abscess: a prospective, randomized trial. J Pediatr Surg 2010;45:236–40. 10.1016/j.jpedsurg.2009.10.039
    1. Lee SL, Islam S, Cassidy LD et al. . Antibiotics and appendicitis in the pediatric population: an American pediatric surgical association outcomes and clinical trials committee systematic review. J Pediatr Surg 2010;45:2181–5. 10.1016/j.jpedsurg.2010.06.038
    1. Rollins KE, Varadhan KK, Neal KR et al. . Antibiotics versus appendectomy for the treatment of uncomplicated acute appendicitis: an updated meta-analysis of randomised controlled trials. World J Surg 2016;40:2305–18. 10.1007/s00268-016-3561-7
    1. Di Salomone S, Sibilio A, Giorgini E et al. . The NOTA study (non operative treatment for acute appendicitis): prospective study on the efficacy and safety of antibiotics (amoxicillin and clavulanic acid) for treating patients with right lower quadrant abdominal pain and long-term follow-up of conservatively treated suspected appendicitis. Ann Surg 2014;260:109–17. 10.1097/SLA.0000000000000560
    1. DiSaverio S, Birindelli A, Kelly MD et al. . WSUS Jerusalem guidelines for diagnosis and treatment of acute appendicitis. World J Emerg Surg 2016;11:34 10.1186/s13017-016-0090-5
    1. Eriksson S, Granström L. Randomized controlled trial of appendicectomy versus antibiotic therapy for acute appendicitis. Br J Surg 1995;82:166–9. 10.1002/bjs.1800820207
    1. Styrud J, Eriksson S, Nilsson I et al. . Appendectomy versus antibiotic treatment in acute appendicitis. A prospective multicentre randomized trial. World J Surg 2006;30:1033–7. 10.1007/s00268-005-0304-6
    1. Varadhan KK, Neal KR, Lobo DN. Safety and efficacy of antibiotics compared with appendicectomy for treatment of uncomplicated acute appendicitis: meta-analysis of randomised controlled trials. BMJ 2012;344:e2156 10.1136/bmj.e2156
    1. Varadhan KK, Humes DJ, Neal KR et al. . Antibiotic therapy versus appendectomy for acute appendicitis: a meta-analysis. World J Surg 2009;34:199–209. 10.1007/s00268-009-0343-5
    1. Liu K, Fogg L. Use of antibiotics alone for treatment of uncomplicated acute appendicitis: a systematic review and meta-analysis. Surgery 2011;150:673–83. 10.1016/j.surg.2011.08.018.
    1. Sallinen V, Akl EA, You JJ et al. . Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicits. Br J Surg 2016;103:656–67. 10.1002/bjs.10147
    1. Salminen P, Paajanen H, Rautio T et al. . Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis . JAMA 2015;313:2340–8. 10.1001/jama.2015.6154
    1. Svensson JF, Patkova B, Almström M et al. . Nonoperative treatment with antibiotics versus surgery for acute nonperforated appendicitis in children. Ann Surg 2015;261:67–71. 10.1097/SLA.0000000000000835
    1. Abeş M, Petik B, Kazil S. Nonoperative treatment of acute appendicitis in children. J Pediatr Surg 2007;42:1439–42. 10.1016/j.jpedsurg.2007.03.049
    1. Armstrong J, Merritt N, Jones S et al. . Non-operative management of early, acute appendicitis in children: Is it safe and effective? J Pediatr Surg 2014;49:782–5. 10.1016/j.jpedsurg.2014.02.071
    1. Koike Y, Uchida K, Matsushita K et al. . Intraluminal appendiceal fluid is a predictive factor for recurrent appendicitis after initial successful non-operative management of uncomplicated appendicitis in pediatric patients. J Pediatr Surgery 2014;49:1116–21. 10.1016/j.jpedsurg.2014.01.003
    1. Steiner Z, Buklan G, Stackievicz R et al. . A role for conservative antibiotic treatment in early appendicitis in children. J Pediatr Surg 2015;50:1566–8. 10.1016/j.jpedsurg.2015.04.008
    1. Gorter RR, van der Lee JH, Cense HA et al. . Initial antibiotic treatment for acute simple appendicitis in children is safe: short-term results from a multicenter, prospective cohort study. Surgery 2015;157:916–23. 10.1016/j.surg.2015.01.008
    1. Kaneko K, Tsuda M. Ultrasound-based decision making in the treatment of acute appendicitis in children. J Pediatr Surg 2004;39:1316–20. 10.1016/j.jpedsurg.2004.05.011
    1. Park HC, Kim BS, Lee BH. Efficacy of short-term antibiotic therapy for consecutive patients with mild appendicitis. Am Surg 2011;77:752–5.
    1. Paudel G, Agrawal C, Regmi R et al. . Conservative treatment in acute appendicitis. JNMA J Nepal Med Assoc 2010;50:295–9.
    1. Caruso AM, Pane A, Garau R et al. . Acute appendicitis in children: not only surgical treatment. J Pediatr Surg 2016;pii: S0022-3468:30277–9. 10.1016/j.pedsurg.2016.08/007.
    1. Hartwich J, Luks FI, Watson-Smith D et al. . Nonoperative treatment of acute appendicitis in children: a feasibility study. J Pediatr Surg 2016;51:111–16. 10.1016/j.jpedsurg.2015.10.024
    1. Minneci PC, Mahida JB, Lodwick DL et al. . Effectiveness of patient choice in nonoperative vs surgical management of pediatric uncomplicated acute appendicitis. JAMA Surg 2016;151:408 10.1001/jamasurg.2015.4534
    1. Tanaka Y, Uchida H, Kawashima H et al. . Long-term outcomes of operative versus nonoperative treatment for uncomplicated appendicitis. J Pediatr Surg 2015;50:1893–7. 10.1016/j.jpedsurg.2015.07.008
    1. Scott IA. Non-inferiority trials: determining whether alternative treatments are good enough. Med J Aust 2009;190:326–30.
    1. Harris PA, Taylor R, Thielke R et al. . Research electronic data capture (REDCap): metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 3009;42:377–81. 10.1016/j.jbi.2008.08.010
    1. Chan A, Tetzlaff J, Gotzsche P et al. . SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ 2013;346:e7586 10.1136/bmj.e7586

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