Lund Heidi, Haijanen Jussi, Suominen Saku, Hurme Saija, Sippola Suvi, Rantanen Tuomo, Rautio Tero, Mattila Anne, Pinta Tarja, Nordström Pia, Kössi Jyrki, Ilves Imre, Salminen Paulina
Division of Digestive Surgery and Urology, Turku University Hospital, Turku, Finland.
Department of Surgery, University of Turku, Turku, Finland.
Scand J Surg. 2025 Mar;114(1):3-12. doi: 10.1177/14574969241293018. Epub 2024 Dec 5.
Antibiotic therapy is currently considered a safe and effective treatment alternative for computed tomography (CT)-confirmed uncomplicated acute appendicitis with recent studies reporting good results on both oral antibiotics only and outpatient management. Furthermore, there are promising pilot results on uncomplicated acute appendicitis management with symptomatic treatment (placebo). This trial aims to assess whether both antibiotics and hospitalization can be safely omitted from the treatment of uncomplicated acute appendicitis.
The APPAC IV (APPendicitis Acuta IV) trial is a randomized, double-blind, multicenter noninferiority clinical trial comparing oral moxifloxacin with oral placebo in an outpatient setting with a discharge directly from the emergency room (ER). Adult patients (18-60 years) with CT-confirmed uncomplicated acute appendicitis (absence of appendicolith, abscess, perforation, tumor, appendiceal diameter ⩾15 mm on CT, or body temperature >38 °C) will be enrolled in nine Finnish hospitals. Primary outcome is treatment success at 30 days, that is, the resolution of acute appendicitis resulting in discharge from the hospital without appendectomy during the 30-day follow-up evaluated using a noninferiority design with a noninferiority margin of 6 percentage points. Noninferiority will be evaluated using one-sided 95% confidence interval of proportion difference between groups. Secondary endpoints include postintervention complications, recurrent appendicitis after the 30-day follow-up, duration of hospital stay, admission to hospital and reason for admission, readmissions to emergency department or hospitalization, VAS pain scores, quality of life, sick leave, and treatment costs. The follow-up after discharge from the ER includes a phone call at day 1, and at 3-4 days, 30 days, and 1, 3, 5, 10, and 20 years. Those eligible patients, who decline to undergo randomization, will be invited to participate in a concurrent observational cohort study with follow-up at 30 days, and 1 and 5 years.
To our knowledge, APPAC IV trial is the first large randomized, double-blind, noninferiority multicenter clinical trial aiming to compare oral antibiotics and placebo for CT-diagnosed uncomplicated acute appendicitis in an outpatient setting. The study aims to bridge the major knowledge gap on whether antibiotics and hospitalization or both can be omitted in the treatment of uncomplicated acute appendicitis.
The study protocol has been approved by the Clinical Trials Information System (CTIS) of the European Medicines Agency (EMA), study number: 2023-506213-21-00 and the trial has been registered in ClinicalTrials.gov, NCT06210269.
目前，抗生素治疗被认为是计算机断层扫描（CT）确诊的非复杂性急性阑尾炎的一种安全有效的治疗选择，近期研究报告显示，仅口服抗生素及门诊治疗均取得了良好效果。此外，针对非复杂性急性阑尾炎进行对症治疗（安慰剂）也取得了有前景的初步结果。本试验旨在评估非复杂性急性阑尾炎治疗中是否可安全地省略抗生素治疗及住院治疗。
APPAC IV（急性阑尾炎IV）试验是一项随机、双盲、多中心非劣效性临床试验，在门诊环境中比较口服莫西沙星与口服安慰剂，并直接从急诊室出院。年龄在18至60岁、CT确诊为非复杂性急性阑尾炎（CT显示无阑尾结石、脓肿、穿孔、肿瘤、阑尾直径≥15mm或体温>38°C）的成年患者将在芬兰的9家医院入组。主要结局是30天时的治疗成功，即急性阑尾炎消退，在30天随访期间无需进行阑尾切除术即可出院，采用非劣效性设计评估，非劣效界值为6个百分点。将使用两组之间比例差异的单侧95%置信区间评估非劣效性。次要终点包括干预后并发症、30天随访后的复发性阑尾炎、住院时间、入院及入院原因、再次急诊就诊或住院、视觉模拟评分法（VAS）疼痛评分、生活质量、病假及治疗费用。从急诊室出院后的随访包括在第1天、3至4天、30天以及1、3、5、10和20年进行电话随访。那些符合条件但拒绝随机分组的患者将被邀请参加一项同期观察性队列研究，随访时间为30天、1年和5年。
据我们所知，APPAC IV试验是第一项大型随机、双盲、非劣效性多中心临床试验，旨在比较口服抗生素和安慰剂在门诊环境中治疗CT诊断的非复杂性急性阑尾炎的效果。该研究旨在弥合非复杂性急性阑尾炎治疗中是否可省略抗生素治疗及住院治疗或两者均可省略这一主要知识空白。
该研究方案已获得欧洲药品管理局（EMA）临床试验信息系统（CTIS）批准，研究编号：2023 - 506213 - 21 - 00，该试验已在ClinicalTrials.gov注册，注册号为NCT06210269。
