A Multicentre, Randomized Controlled Trial Comparing Appendectomy Versus Non-Operative Treatment For Acute Non-Perforated Appendicitis in Children
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 978
- 试验地点
- 2
- 主要终点
- treatment failure
研究概览
简要总结
Rationale and Aim: The standard treatment for acute appendicitis in children is appendectomy. An increasing body of evidence from the adult literature suggests that acute appendicitis may be treated effectively with antibiotics alone, avoiding the need for surgery. The aim of this study is to investigate the effectiveness of non-operative treatment of acute appendicitis in children.
Study design: Pragmatic, parallel-group, unmasked, non-inferiority multicentre randomized controlled trial (RCT).
Patient allocation: Children will be randomly allocated (age 5-16 years) with a diagnosis of acute appendicitis to either laparoscopic appendectomy or treatment with antibiotics. Randomization will be performed using stratification to ensure equal distribution between groups of presenting clinical and demographic features that may influence outcome including gender, duration of symptoms and center.
Interventions: One group of children will undergo laparoscopic appendectomy that is the current standard treatment for children with acute appendicitis. The other group will be treated with intravenous antibiotics. A treatment pathway specifically designed for this study will be used.
Primary Outcome: To be meaningful to parents of, and clinicians treating, children with acute appendicitis, the primary outcome is treatment failure defined as: (i) any additional intervention related to appendicitis requiring general anesthesia within 1 year of randomization (including recurrence of appendicitis after non-operative treatment, which we will treat with appendectomy) or (ii) negative appendectomy. Secondary outcomes are: (i) complications; (ii) time to discharge following randomization; (iii) number and duration of hospital admissions.
Sample size and data analysis: The proposed RCT has a 20% non-inferiority margin to test the null hypothesis that treatment with antibiotics is inferior to appendectomy. Based on data from collaborating centers and a pilot study that we have performed, we expect recruitment of 978 children in total (90% power) over 19 months allowing for drop out. Follow-up will be for 12 months.
详细描述
Background Acute appendicitis is the commonest surgical emergency in children. The lifetime risk of developing appendicitis is 7-8%, with a peak incidence in the teenage years.The associated financial burden of treating appendicitis is very large.
For over 100 years, surgical removal of the appendix has been deemed necessary to effectively treat acute appendicitis. Appendectomy remains the cornerstone of treatment for acute appendicitis, with the exception of phlegmon or appendix mass. However, in recent years this surgical dogma has been challenged and there is a growing literature to suggest that antibiotics without surgery may be an effective treatment for acute appendicitis in adults and more recently in children. However this non-operative management of acute appendicitis remains controversial and unproven due to the lack of large prospective randomized controlled trials.
Although appendectomy is generally a simple procedure, it requires general anesthesia and is an abdominal operation with inherent risks and potential complications. Complications related to surgery or anesthesia events occur in over 10% of children within 30 days of appendectomy. Although a non-operative approach may avoid these risks and reduce complication rate, this would not be a viable alternative to surgery unless it is equally effective at curing acute appendicitis.
The existing literature relating to the efficacy of non-operative treatment of acute appendicitis in predominantly from adult patients. Several trials and systematic reviews have been reported. A most recent meta-analysis concluded that there were benefits to non-operative treatment including fewer complications, better pain control, and shorter sick leave but that the combined failure and recurrence rate in patients treated non-operatively made this approach less effective overall.
In children, the literature is limited. The most significant studies are: Abes et al [6] who described successful, non-operative treatment in 15 of 16 children who had a very short duration of illness, and minimal diagnostic criteria on imaging; Armstrong et al [7] who reported a 75% success rate in 12 children treated non-operatively along with a matched comparison group undergoing surgery; two RCTs from the USA that compared appendectomy with antibiotic treatment for children with perforated appendicitis [8,9] (a different patient group from the one which we intend to study); a single centre, preference-based, non-randomized study comparing laparoscopic appendectomy with antibiotic treatment [10] that reported interim results only.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •children (age 5-16 years)
- •clinical and /or radiological diagnosis (ultrasound [US] and/or CT scan) of acute non-perforated appendicitis
- •written informed parental/legal guardian permission in accordance with local regulations and institutional policy
- •written informed child assent or waiver in accordance with local regulations and institutional policy
排除标准
- •suspicion of perforated appendicitis
- •presentation with an appendix mass or phlegmon (on physical examination and/or imaging)
- •non-operative management (2 or more rounds of intravenous antibiotics) initiated at an outside institution
- •previous episode of appendicitis or appendix mass/phlegmon treated non-operatively
- •current treatment for malignancy
- •positive pregnancy test (if part of a clinical routine)
- •diagnosis of Cystic Fibrosis (CF)
结局指标
主要结局
treatment failure
时间窗: within 1 year of randomization
The primary outcome is treatment failure. Treatment failure is defined as: (i) additional intervention related to appendicitis requiring general anesthesia within 1 year of randomization (this includes the recurrence of appendicitis after non-operative treatment, which will be treated with appendectomy) or (ii) negative appendectomy. This definition of the primary outcome will capture all important parameters in both treatment groups including specifically: failure of antibiotic treatment requiring appendectomy, significant complication (defined as requiring general anaesthesia) in either treatment group, recurrence of acute appendicitis (treated by appendectomy) and negative appendectomy.
次要结局
- time to discharge(1 year from randomization)
- number and duration of hospital admissions(within 1 year of randomization)
- complications(within 1 year of randomization)
- treatment efficacy(within 1 year of randomization)
研究者
Shawn St. Peter
Shawn St. Peter, MD, Director of Research, Department of Surgery
Children's Mercy Hospital Kansas City