Effect of Oral Moxifloxacin vs Intravenous Ertapenem Plus Oral Levofloxacin for Treatment of Uncomplicated Acute Appendicitis: The APPAC II Randomized Clinical Trial

• Published in: JAMA : the journal of the American Medical Association 2021-01, Vol.325 (4), p.353-362
• Main Authors: Sippola, Suvi, Haijanen, Jussi, Grönroos, Juha, Rautio, Tero, Nordström, Pia, Rantanen, Tuomo, Pinta, Tarja, Ilves, Imre, Mattila, Anne, Rintala, Jukka, Löyttyniemi, Eliisa, Hurme, Saija, Tammilehto, Ville, Marttila, Harri, Meriläinen, Sanna, Laukkarinen, Johanna, Sävelä, Eeva-Liisa, Savolainen, Heini, Sippola, Tomi, Aarnio, Markku, Paajanen, Hannu, Salminen, Paulina
• Format: Article
• Language: English
• Subjects: Acute Disease; Administration, Intravenous; Administration, Oral; Adult; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Antibiotics; Appendectomy; Appendicitis; Appendicitis - diagnostic imaging; Appendicitis - drug therapy; Appendicitis - surgery; Clinical trials; Computed tomography; Confidence limits; Drug Therapy, Combination; Ertapenem; Ertapenem - therapeutic use; Female; Follow-Up Studies; Health services; Humans; Intravenous administration; Levofloxacin; Levofloxacin - therapeutic use; Male; Metronidazole; Metronidazole - therapeutic use; Middle Aged; Moxifloxacin; Moxifloxacin - therapeutic use; Online First; Original Investigation; Patients; Success; Surgery; Tomography, X-Ray Computed; Young Adult
• ISSN: 0098-7484; 1538-3598; 1538-3598
• DOI: 10.1001/jama.2020.23525

IMPORTANCE: Antibiotics are an effective and safe alternative to appendectomy for managing uncomplicated acute appendicitis, but the optimal antibiotic regimen is not known. OBJECTIVE: To compare oral antibiotics with combined intravenous followed by oral antibiotics in the management of computed tomography–confirmed uncomplicated acute appendicitis. DESIGN, SETTING, AND PARTICIPANTS: The Appendicitis Acuta (APPAC) II multicenter, open-label, noninferiority randomized clinical trial was conducted from April 2017 until November 2018 in 9 Finnish hospitals. A total of 599 patients aged 18 to 60 years with computed tomography–confirmed uncomplicated acute appendicitis were enrolled in the trial. The last date of follow-up was November 29, 2019. INTERVENTIONS: Patients randomized to receive oral monotherapy (n = 295) received oral moxifloxacin (400 mg/d) for 7 days. Patients randomized to receive intravenous antibiotics followed by oral antibiotics (n = 288) received intravenous ertapenem (1 g/d) for 2 days followed by oral levofloxacin (500 mg/d) and metronidazole (500 mg 3 times/d) for 5 days. MAIN OUTCOMES AND MEASURES: The primary end point was treatment success (≥65%) for both groups, defined as discharge from hospital without surgery and no recurrent appendicitis during 1-year follow-up, and to determine whether oral antibiotics alone were noninferior to intravenous and oral antibiotics, with a margin of 6% for difference. RESULTS: Among 599 patients who were randomized (mean [SD] age, 36 [12] years; 263 [44%] women), 581 (99.7%) were available for the 1-year follow-up. The treatment success rate at 1 year was 70.2% (1-sided 95% CI, 65.8% to ∞) for patients treated with oral antibiotics and 73.8% (1-sided 95% CI, 69.5% to ∞) for patients treated with intravenous followed by oral antibiotics. The difference was −3.6% ([1-sided 95% CI, −9.7% to ∞]; P = .26 for noninferiority), with the confidence limit exceeding the noninferiority margin. CONCLUSION AND RELEVANCE: Among adults with uncomplicated acute appendicitis, treatment with 7 days of oral moxifloxacin compared with 2 days of intravenous ertapenem followed by 5 days of levofloxacin and metronidazole resulted in treatment success rates greater than 65% in both groups, but failed to demonstrate noninferiority for treatment success of oral antibiotics compared with intravenous followed by oral antibiotics. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03236961; EudraCT Identifier: 2015-003633-10