van den Boom Anne Loes, de Wijkerslooth Elisabeth M L, van Rosmalen Joost, Beverdam Frédérique H, Boerma Evert-Jan G, Boermeester Marja A, Bosmans Joanna W A M, Burghgraef Thijs A, Consten Esther C J, Dawson Imro, Dekker Jan Willem T, Emous Marloes, van Geloven Anna A W, Go Peter M N Y H, Heijnen Luc A, Huisman Sander A, Jean Pierre Dayanara, de Jonge Joske, Kloeze Jurian H, Koopmanschap Marc A, Langeveld Hester R, Luyer Misha D P, Melles Damian C, Mouton Johan W, van der Ploeg Augustinus P T, Poelmann Floris B, Ponten Jeroen E H, van Rossem Charles C, Schreurs Wilhelmina H, Shapiro Joël, Steenvoorde Pascal, Toorenvliet Boudewijn R, Verhelst Joost, Versteegh Hendt P, Wijnen Rene M H, Wijnhoven Bas P L
Department of Surgery, Erasmus MC - University Medical Centre Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Department of Biostatistics, Erasmus MC - University Medical Centre, Rotterdam, The Netherlands.
Trials. 2018 May 2;19(1):263. doi: 10.1186/s13063-018-2629-0.
Acute appendicitis is one of the most common indications for emergency surgery. In patients with a complex appendicitis, prolonged antibiotic prophylaxis is recommended after appendectomy. There is no consensus regarding the optimum duration of antibiotics. Guidelines propose 3 to 7 days of treatment, but shorter courses may be as effective in the prevention of infectious complications. At the same time, the global issue of increasing antimicrobial resistance urges for optimization of antibiotic strategies. The aim of this study is to determine whether a short course (48 h) of postoperative antibiotics is non-inferior to current standard practice of 5 days.
Patients of 8 years and older undergoing appendectomy for acute complex appendicitis - defined as a gangrenous and/or perforated appendicitis or appendicitis in presence of an abscess - are eligible for inclusion. Immunocompromised or pregnant patients are excluded, as well as patients with a contraindication to the study antibiotics. In total, 1066 patients will be randomly allocated in a 1:1 ratio to the experimental treatment arm (48 h of postoperative intravenously administered (IV) antibiotics) or the control arm (5 days of postoperative IV antibiotics). After discharge from the hospital, patients participate in a productivity-cost-questionnaire at 4 weeks and a standardized telephone follow-up at 90 days after appendectomy. The primary outcome is a composite endpoint of infectious complications, including intra-abdominal abscess (IAA) and surgical site infection (SSI), and mortality within 90 days after appendectomy. Secondary outcomes include IAA, SSI, restart of antibiotics, length of hospital stay (LOS), reoperation, percutaneous drainage, readmission rate, and cost-effectiveness. The non-inferiority margin for the difference in the primary endpoint rate is set at 7.5% (one-sided test at ɑ 0.025). Both per-protocol and intention-to-treat analyses will be performed.
This trial will provide evidence on whether 48 h of postoperative antibiotics is non-inferior to a standard course of 5 days of antibiotics. If non-inferiority is established, longer intravenous administration following appendectomy for complex appendicitis can be abandoned, and guidelines need to be adjusted accordingly.
Dutch Trial Register, NTR6128 . Registered on 20 December 2016.
急性阑尾炎是急诊手术最常见的指征之一。对于复杂性阑尾炎患者，建议阑尾切除术后延长抗生素预防时间。关于抗生素的最佳使用时长尚无共识。指南建议治疗3至7天，但更短疗程在预防感染并发症方面可能同样有效。与此同时，全球抗菌药物耐药性增加的问题促使人们优化抗生素策略。本研究的目的是确定术后短期（48小时）使用抗生素是否不劣于目前5天的标准治疗方案。
年龄在8岁及以上、因急性复杂性阑尾炎（定义为坏疽性和/或穿孔性阑尾炎或伴有脓肿的阑尾炎）接受阑尾切除术的患者符合纳入条件。免疫功能低下或怀孕的患者以及对研究用抗生素有禁忌证的患者被排除。总共1066名患者将按1:1的比例随机分配至试验治疗组（术后静脉注射抗生素48小时）或对照组（术后静脉注射抗生素5天）。出院后，患者在术后4周参与一份生产力-成本调查问卷，并在阑尾切除术后90天接受标准化电话随访。主要结局是感染并发症的复合终点，包括腹腔内脓肿（IAA）和手术部位感染（SSI），以及阑尾切除术后90天内的死亡率。次要结局包括IAA、SSI、抗生素再使用、住院时间（LOS）、再次手术、经皮引流、再入院率和成本效益。主要终点率差异的非劣效界值设定为7.5%（ɑ = 0.025时的单侧检验）。将进行符合方案分析和意向性分析。
本试验将提供证据，证明术后48小时使用抗生素是否不劣于5天的标准抗生素疗程。如果确立了非劣效性，则可放弃复杂性阑尾炎阑尾切除术后较长时间的静脉给药，相应地，指南也需要调整。
荷兰试验注册中心，NTR6128。于2016年12月20日注册。
