A randomized clinical single-center trial comparing antibiotics to surgery for the treatment of computed tomography-uncomplicated acute appendicitis in adults: the Kouba non operative management of acute appendicitis trial protocol


  • Hani Bendib Department of Oncologic Surgery, Debussy Clinic, Algiers, Algeria Faculty of Medicine, Algiers 1 University, Algeria http://orcid.org/0000-0003-2547-3130
  • Mohamed Hadj Department of General Surgery, Kouba Hospital, Algiers, Algeria
  • Mohamed Rafik Slimani Faculty of Medicine, Algiers 1 University, Algeria Department of General Surgery, Kouba Hospital, Algiers, Algeria
  • Meriem Kissar Department of General Surgery, Kouba Hospital, Algiers, Algeria
  • Mohamed Melouka Department of General Surgery, Kouba Hospital, Algiers, Algeria




Acute appendicitis, Appendectomy, Antibiotic therapy, Non operative management


Background: Several Western studies support the idea that some acute appendicitis (AA) can be successfully treated by antibiotics. The rationale for the non-operative treatment is essentially based on the non-futility of the vermicular appendix which seems to play a major role in the pathophysiology of the digestive tract. However, this approach still suffers from a failure rate of around 20-30% in the first year, rising to nearly half of patients within 5 years. In Algeria, appendectomy is still the standard of care. Through rigorous selection, the Kouba non operative management of acute appendicitis (KNOMA) trial aims to determine whether non-operative treatment (NOT) is non-inferior to surgery.

Methods: KNOMA is a randomized, controlled, non-inferiority trial designed to enroll 180 adults with CT-confirmed uncomplicated AA. Participants are randomized to appendectomy or 9 days of antibiotics (Abx). The primary endpoint is the failure rate at 12 months. This trial was designed to take into account the specifics of the Algerian population and practices in Algeria.

Conclusions: This is the first trial in Africa and middle-income countries to evaluate the comparative efficacy of antibiotics and appendectomy for the treatment of CT-confirmed uncomplicated acute appendicitis based on failure rate assessment.

Trial registration: This trial was registered on pactr.org on 28 March 2022 (PACTR202203751640059).


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Ferris M, Quan S, Kaplan BS, Molodecky N, Ball CG, Chernoff GW, et al. The global incidence of appendicitis: a systematic review of population-based studies. Ann Surg. 2017;266:237-41.

Krzyzak M, Mulrooney SM. Acute Appendicitis Review: Background, Epidemiology, Diagnosis, and Treatment. Cureus. 2012;12:e8562.

Jaschinski T, Mosch C, Eikermann M, Neugebauer EA. Laparoscopic versus open appendectomy in patients with suspected appendicitis: a systematic review of meta-analyses of randomised controlled trials. BMC Gastroenterol. 2015;15:48.

Snyder MJ, Guthrie M, Cagle S. Acute Appendicitis: Efficient Diagnosis and Management. 2018; 98: 10.

Livingston E, Vons C. Treating Appendicitis Without Surgery. JAMA. 2015;313:2327-8.

Eriksson S, Granström L. Randomized controlled trial of appendicectomy versus antibiotic therapy for acute appendicitis. Br J Surg. 1995;82:166-9.

Styrud J, Eriksson S, Nilsson I, Ahlberg G, Haapaniemi S, Neovius G, et al. Appendectomy versus antibiotic treatment in acute appendicitis. a prospective multicenter randomized controlled trial. World J Surg. 2006;30:1033-7.

Hansson J, Körner U, Khorram-Manesh A, Solberg A, Lundholm K. Randomized clinical trial of antibiotic therapy versus appendicectomy as primary treatment of acute appendicitis in unselected patients. Br J Surg. 2009;96:473-81.

Vons C, Barry C, Maitre S, Pautrat K, Leconte M, Costaglioli B, et al. Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial. The Lancet. 2011;377:1573-9.

Salminen P, Paajanen H, Rautio T, Nordström P, Aarnio M, Rantanen T, et al. Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial. JAMA. 2015;313:2340.

Flum F. A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis. N Eng J Med. 2020;383:1907-19.

Sallinen V, Akl EA, You JJ, Agarwal A, Shoucair S, Vandvik PO, et al. Meta‐analysis of antibiotics versus appendicectomy for non‐perforated acute appendicitis. Br J Surg. 2016;103:656-67.

Harnoss JC, Zelienka I, Probst P, Grummich K, Müller-Lantzsch C, Harnoss JM, et al. Antibiotics Versus Surgical Therapy for Uncomplicated Appendicitis: Systematic Review and Meta-analysis of Controlled Trials (PROSPERO 2015: CRD42015016882). Ann Surg. 2017;265:889-900.

Podda M, Gerardi C, Cillara N, Fearnhead N, Gomes CA, Birindelli A, et al. Antibiotic Treatment and Appendectomy for Uncomplicated Acute Appendicitis in Adults and Children: A Systematic Review and Meta-analysis. Ann Surg. 2019;270:1028-40.

Salminen P, Tuominen R, Paajanen H, Rautio T, Nordström P, Aarnio M, et al. Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial. JAMA. 2018;320:1259-65.

Sippola S, Grönroos J, Tuominen R, Paajanen H, Rautio T, Nordström P, et al. Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial. Br J Surg. 2017;104:1355-61.

Sippola S, Haijanen J, Viinikainen L, Grönroos J, Paajanen H, Rautio T, et al. Quality of Life and Patient Satisfaction at 7-Year Follow-up of Antibiotic Therapy vs Appendectomy for Uncomplicated Acute Appendicitis. JAMA Surg. 2020;e196028.

Haijanen J, Sippola S, Tuominen R, Grönroos J, Paajanen H, Rautio T, et al. Cost analysis of antibiotic therapy versus appendectomy for treatment of uncomplicated acute appendicitis: 5-year results of the APPAC randomized clinical trial. PLoS One. 2019;14:e0220202.

Di Saverio S, Podda M, De Simone B, Ceresoli M, Augustin G, Gori A, et al. Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines. World J Emerg Surg. 2020;15:27.

De Coppi P, Pozzobon M, Piccoli M, Gazzola MV, Boldrin L, Slanzi E, et al. Isolation of mesenchymal stem cells from human vermiform appendix. J Surg Res. 2006;135:85-91.

Randal Bollinger R, Barbas AS, Bush EL, Lin SS, Parker W. Biofilms in the large bowel suggest an apparent function of the human vermiform appendix. J Theor Biol. 2007;249:826-31.

Federico C, Paola F, Massimo S, Enrico C, Maria GS, Gioacchino L, et al. Conservative treatment of acute appendicitis. Acta Biomed. 2018;89:119-34.

Andersson RE. Small bowel obstruction after appendicectomy. Br J Surg. 2001;88:1387-91.

Duron JJ, Hay JM, Msika S, Gaschard D, Domergue J, Gainant A, et al. Prevalence and mechanisms of small intestinal obstruction following laparoscopic abdominal surgery: a retrospective multicenter study. French Association for Surgical Research. Arch Surg. 2000;135:208-12.

Leung TTW, Dixon E, Gill M, Mador BD, Moulton KM, Kaplan GG, et al. Bowel obstruction following appendectomy: what is the true incidence? Ann Surg. 2009;250:51-3.

Allievi N, Harbi A, Ceresoli M, Montori G, Poiasina E, Coccolini F, et al. Acute Appendicitis: Still a Surgical Disease? Results from a Propensity Score-Based Outcome Analysis of Conservative Versus Surgical Management from a Prospective Database. World J Surg. 2017;41:2697-705.

Flum DR, Koepsell T. The clinical and economic correlates of misdiagnosed appendicitis: nationwide analysis. Arch Surg. 2002;137:799-804.

Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020;91:157-60.

Andersson M, Kolodziej B, Andersson RE, STRAPPSCORE Study Group. Randomized clinical trial of Appendicitis Inflammatory Response score-based management of patients with suspected appendicitis. Br J Surg. 2017;104:1451-61.

Kularatna M, Lauti M, Haran C, MacFater W, Sheikh L, Huang Y, et al. Clinical Prediction Rules for Appendicitis in Adults: Which Is Best? World J Surg. 2017;41:1769-81.

Schug-Pass C, Geers P, Hügel O, Lippert H, Köckerling F. Prospective randomized trial comparing short-term antibiotic therapy versus standard therapy for acute uncomplicated sigmoid diverticulitis. Int J Colorectal Dis. 2010;25:751-9.

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205-13.

EuroQol Group. EuroQol-a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199-208.

World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310:2191-4.

Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 Statement: Updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol. 2010;63:834-40.

Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, et al. SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials. Ann Intern Med. 2013;158:200-7.

ICMJE, Recommendations, Defining the Role of Authors and Contributors. Available at: https://www.icmje.org/recommendations/browse/roles-and-responsibilities/defining-the-role-of-authors-and-contributors.html. Accessed on 2022 Apr 24.

Brunner M, Lapins P, Langheinrich M, Baecker J, Krautz C, Kersting S, et al. Risk factors for appendiceal neoplasm and malignancy among patients with acute appendicitis. Int J Colorectal Dis. 2020;35:157-63.

Kollár D, McCartan DP, Bourke M, Cross KS, Dowdall J. Predicting acute appendicitis? A comparison of the Alvarado score, the Appendicitis Inflammatory Response Score and clinical assessment. World J Surg. 2015;39:104-9.