Optimising the antibiotic treatment of uncomplicated acute appendicitis: a protocol for a multicentre randomised clinical trial (APPAC II trial)
Optimising the antibiotic treatment of uncomplicated acute appendicitis: a protocol for a multicentre randomised clinical trial (APPAC II trial)
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DOI：
10.1186/s12893-018-0451-y
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发表时间：
2018-12-17
期刊：
影响因子：
1.9
通讯作者：
Salminen, P.
中科院分区：
文献类型：
--
作者：
Haijanen, J.;Sippola, S.;Salminen, P.
根据流行病学和临床资料，急性阑尾炎可表现为单纯性（70-80%）或复杂性（20-30%）疾病。最近的研究表明，抗生素治疗是安全和成本效益的CT扫描证实无并发症急性阑尾炎。然而，基于确保患者安全性的研究方案，这些随机研究主要使用广谱静脉注射抗生素，需要额外的医院资源和延长的住院时间。正如我们现在所知，抗生素治疗无并发症的急性阑尾炎是可行且安全的，需要进一步研究评估抗生素治疗在抗生素谱和更短住院时间方面的优化，以评估抗生素作为无并发症的急性阑尾炎的一线治疗方法APPAC II试验是一项多中心、开放标签、非劣效性随机对照试验，比较口服（口服）抗生素单一疗法与静脉内（i. v.）抗生素治疗后口服抗生素治疗CT扫描证实的无并发症急性阑尾炎。经CT扫描诊断为无并发症急性阑尾炎的成人患者将在9家芬兰医院入组。预期样本量为552例患者。主要终点是随机治疗的成功，定义为急性阑尾炎消退，无需手术干预即可出院，并且在一年随访期间没有复发阑尾炎。次要终点包括干预后并发症、一年后急性阑尾炎晚期复发、住院时间、疼痛、生活质量、病假和治疗费用。将分两个阶段评价主要终点：将计算两组的点估计值和95%置信区间（CI），并计算组间的比例差异和95% CI，并基于6个百分点的非劣效性界值进行评价。讨论据我们所知，APPAC II试验是第一项比较口服抗生素单药治疗与静脉注射抗生素治疗的随机对照试验，口服抗生素治疗单纯性急性阑尾炎APPAC II试验旨在为抗生素作为CT证实的无并发症急性阑尾炎的一线治疗的争议作用提供临床证据，并优化无并发症急性阑尾炎的非手术治疗。试验registrationClinicaltrials.gov，NCT 03236961，于2017年8月2日回顾性注册。
BackgroundBased on epidemiological and clinical data acute appendicitis can present either as uncomplicated (70-80%) or complicated (20-30%) disease. Recent studies have shown that antibiotic therapy is both safe and cost-effective for a CT-scan confirmed uncomplicated acute appendicitis. However, based on the study protocols to ensure patient safety, these randomised studies used mainly broad-spectrum intravenous antibiotics requiring additional hospital resources and prolonged hospital stay. As we now know that antibiotic therapy for uncomplicated acute appendicitis is feasible and safe, further studies evaluating optimisation of the antibiotic treatment regarding both antibiotic spectrum and shorter hospital stay are needed to evaluate antibiotics as the first-line treatment for uncomplicated acute appendicitis.MethodsAPPAC II trial is a multicentre, open-label, non-inferiority randomised controlled trial comparing per oral (p.o.) antibiotic monotherapy with intravenous (i.v.) antibiotic therapy followed by p.o. antibiotics in the treatment of CT-scan confirmed uncomplicated acute appendicitis. Adult patients with CT-scan diagnosed uncomplicated acute appendicitis will be enrolled in nine Finnish hospitals. The intended sample size is 552 patients.Primary endpoint is the success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without the need for surgical intervention and no recurrent appendicitis during one-year follow-up. Secondary endpoints include post-intervention complications, late recurrence of acute appendicitis after one year, duration of hospital stay, pain, quality of life, sick leave and treatment costs. Primary endpoint will be evaluated in two stages: point estimates with 95% confidence interval (CI) will be calculated for both groups and proportion difference between groups with 95% CI will be calculated and evaluated based on 6 percentage point non-inferiority margin.DiscussionTo our knowledge, APPAC II trial is the first randomised controlled trial comparing per oral antibiotic monotherapy with intravenous antibiotic therapy continued by per oral antibiotics in the treatment of uncomplicated acute appendicitis. The APPAC II trial aims to add clinical evidence on the debated role of antibiotics as the first-line treatment for a CT-confirmed uncomplicated acute appendicitis as well as to optimise the non-operative treatment for uncomplicated acute appendicitis.Trial registrationClinicaltrials.gov, NCT03236961, retrospectively registered on the 2nd of August 2017.