A prospective randomized controlled multicenter trial comparing antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis (APPAC trial)

Hannu Paajanen, Juha M Grönroos, Tero Rautio, Pia Nordström, Markku Aarnio, Tuomo Rantanen, Saija Hurme, Kirsti Dean, Airi Jartti, Jukka-Pekka Mecklin, Juhani Sand, Paulina Salminen, Hannu Paajanen, Juha M Grönroos, Tero Rautio, Pia Nordström, Markku Aarnio, Tuomo Rantanen, Saija Hurme, Kirsti Dean, Airi Jartti, Jukka-Pekka Mecklin, Juhani Sand, Paulina Salminen

Abstract

Background: Although the standard treatment of acute appendicitis (AA) consists of an early appendectomy, there has recently been both an interest and an increase in the use of antibiotic therapy as the primary treatment for uncomplicated AA. However, the use of antibiotic therapy in the treatment of uncomplicated AA is still controversial.

Methods/design: The APPAC trial is a randomized prospective controlled, open label, non-inferiority multicenter trial designed to compare antibiotic therapy (ertapenem) with emergency appendectomy in the treatment of uncomplicated AA. The primary endpoint of the study is the success of the randomized treatment. In the antibiotic treatment arm successful treatment is defined as being discharged from the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of one-year (treatment efficacy). Treatment efficacy in the operative treatment arm is defined as successful appendectomy evaluated to be 100%. Secondary endpoints are post-intervention complications, overall morbidity and mortality, the length of hospital stay and sick leave, treatment costs and pain scores (VAS, visual analoque scale). A maximum of 610 adult patients (aged 18-60 years) with a CT scan confirmed uncomplicated AA will be enrolled from six hospitals and randomized by a closed envelope method in a 1:1 ratio either to undergo emergency appendectomy or to receive ertapenem (1 g per day) for three days continued by oral levofloxacin (500 mg per day) plus metronidazole (1.5 g per day) for seven days. Follow-up by a telephone interview will be at 1 week, 2 months and 1, 3, 5 and 10 years; the primary and secondary endpoints of the trial will be evaluated at each time point.

Discussion: The APPAC trial aims to provide level I evidence to support the hypothesis that approximately 75-85% of patients with uncomplicated AA can be treated with effective antibiotic therapy avoiding unnecessary appendectomies and the related operative morbidity, also resulting in major cost savings.

Trial registration: ClinicalTrials.gov NCT01022567.

References

    1. Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol. 1990;132(5):910–925.
    1. DeFrances CJ, Podgornik MN. National hospital discharge survey. Adv Data. 2004;2006(371):1–19.
    1. Ilves I, Paajanen HE, Herzig KH, Fagerstrom A, Miettinen PJ. Changing incidence of acute appendicitis and nonspecific abdominal pain between 1987 and 2007 in Finland. World J Surg. 2011;35(4):731–738. doi: 10.1007/s00268-011-0988-8.
    1. Ditillo MF, Dziura JD, Rabinovici R. Is it safe to delay appendectomy in adults with acute appendicitis? Ann Surg. 2006;244(5):656–660. doi: 10.1097/01.sla.0000231726.53487.dd.
    1. Wilms IM, De Hoog DE, De Visser DC, Janzing HM. Appendectomy versus antibiotic treatment for acute appendicitis. Cochrane Database Syst Rev. 2011;9(11):CD008359.
    1. Ansaloni L, Catena F, Coccolini F, Ercolani G, Gazzotti F, Pasqualini E, Pinna AD. Surgery versus conservative antibiotic treatment in acute appendicitis: a systematic review and meta-analysis of randomized controlled trials. Dig Surg. 2011;28(3):210–221. doi: 10.1159/000324595.
    1. Liu K, Fogg L. Use of antibiotics alone for treatment of uncomplicated acute appendicitis: a systematic review and meta-analysis. Surgery. 2011;150(4):673–683. doi: 10.1016/j.surg.2011.08.018.
    1. Mason RJ, Moazzez A, Sohn H, Katkhouda N. Meta-analysis of randomized trials comparing antibiotic therapy with appendectomy for acute uncomplicated (no abscess or phlegmon) appendicitis. Surg Infect (Larchmt) 2012;13(2):74–84. doi: 10.1089/sur.2011.058.
    1. Varadhan KK, Humes DJ, Neal KR, Lobo DN. Antibiotic therapy versus appendectomy for acute appendicitis: a meta-analysis. World J Surg. 2010;34(2):199–209. doi: 10.1007/s00268-009-0343-5.
    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. doi: 10.1136/bmj.e2156.
    1. Mason RJ. Surgery for appendicitis: is it necessary? Surg Infect (Larchmt) 2008;9(4):481–488. doi: 10.1089/sur.2007.079.
    1. Sakorafas GH, Mastoraki A, Lappas C, Sampanis D, Danias N, Smyrniotis V. Conservative treatment of acute appendicitis: heresy or an effective and acceptable alternative to surgery? Eur J Gastroenterol Hepatol. 2011;23(2):121–127. doi: 10.1097/MEG.0b013e32834233b6.
    1. Eriksson S, Granstrom L. Randomized controlled trial of appendicectomy versus antibiotic therapy for acute appendicitis. Br J Surg. 1995;82(2):166–169. doi: 10.1002/bjs.1800820207.
    1. Hansson J, Korner 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(5):473–481. doi: 10.1002/bjs.6482.
    1. Malik AA, Bari SU. Conservative management of acute appendicitis. J Gastrointest Surg. 2009;13(5):966–970. doi: 10.1007/s11605-009-0835-5.
    1. Styrud J, Eriksson S, Nilsson I, Ahlberg G, Haapaniemi S, Neovius G, Rex L, Badume I, Granstrom L. Appendectomy versus antibiotic treatment in acute appendicitis. a prospective multicenter randomized controlled trial. World J Surg. 2006;30(6):1033–1037. doi: 10.1007/s00268-005-0304-6.
    1. Vons C, Barry C, Maitre S, Pautrat K, Leconte M, Costaglioli B, Karoui M, Alves A, Dousset B, Valleur P, Falissard B, Franco D. Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial. Lancet. 2011;377(9777):1573–1579. doi: 10.1016/S0140-6736(11)60410-8.
    1. Farahnak M, Talaei-Khoei M, Gorouhi F, Jalali A. The Alvarado score and antibiotics therapy as a corporate protocol versus conventional clinical management: randomized controlled pilot study of approach to acute appendicitis. Am J Emerg Med. 2007;25(7):850–852. doi: 10.1016/j.ajem.2007.01.012.
    1. Horton MD, Counter SF, Florence MG, Hart MJ. A prospective trial of computed tomography and ultrasonography for diagnosing appendicitis in the atypical patient. Am J Surg. 2000;179(5):379–381. doi: 10.1016/S0002-9610(00)00372-X.
    1. Rao PM, Rhea JT, Novelline RA, Mostafavi AA, McCabe CJ. Effect of computed tomography of the appendix on treatment of patients and use of hospital resources. N Engl J Med. 1998;338(3):141–146. doi: 10.1056/NEJM199801153380301.
    1. Coursey CA, Nelson RC, Patel MB, Cochran C, Dodd LG, Delong DM, Beam CA, Vaslef S. Making the diagnosis of acute appendicitis: do more preoperative CT scans mean fewer negative appendectomies? A 10-year study. Radiology. 2010;254(2):460–468. doi: 10.1148/radiol.09082298.
    1. Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ, O’Neill PJ, Chow AW, Dellinger EP, Eachempati SR, Gorbach S, Hilfiker M, May AK, Nathens AB, Sawyer RG, Bartlett JG. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the surgical infection society and the infectious diseases society of america. Surg Infect (Larchmt) 2010;11(1):79–109. doi: 10.1089/sur.2009.9930.
    1. Sahani DV SA. Abdominal imaging. Saunders Elsevier; 2011. pp. 190–194.
    1. ), U.S.F.a.D.A. 2007.
    1. Shrestha B. Antibiotics versus surgery for appendicitis. Lancet. 2011;378(9796):1067. author reply 1068.
    1. Shindoh J, Niwa H, Kawai K, Ohata K, Ishihara Y, Takabayashi N, Kobayashi R, Hiramatsu T. Predictive factors for negative outcomes in initial non-operative management of suspected appendicitis. J Gastrointest Surg. 2010;14(2):309–314. doi: 10.1007/s11605-009-1094-1.
    1. Mazuski JE, Solomkin JS. Intra-abdominal infections. Surg Clin North Am. 2009;89(2):421–437. doi: 10.1016/j.suc.2008.12.001. ix.

Source: PubMed

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