Non-Operative Management of Pediatric Appendicitis: A Randomized Controlled Study

Rhode Island Hospital, Providence RI

Investigators

Abstract

Project Summary Acute appendicitis is the most common surgical emergency in children, with 70,000 cases per year in the United States. Early diagnosis and urgent appendectomy have virtually eliminated its mortality, but any surgical intervention is associated with pain, discomfort and risk of complications. Because appendicitis is so common, it represents a significant overall health care burden. Several adult randomized controlled trials (RCTs) of appendicitis have found that early disease may be safely treated with antibiotics alone. In the last 3 years, 8 small studies have suggested that non-operative management may also be applicable to pediatric appendicitis. The pooled success rate in over 400 patients was 73% (range: 62-87%). While encouraging, important clinical knowledge gaps remain. Given small study size, heterogeneous methods and populations, and few reported complications, the true complication rate, safety, efficacy, cost, and health utility of non-operative management of acute appendicitis in children is unknown. We propose the first large RCT comparing urgent appendectomy and non-operative management of acute appendicitis in children. Its overarching goal is to determine whether it is reasonable to manage these children non-operatively. Our four Specific Aims are: 1) to establish the infrastructure, collaborators and processes for a multicenter pediatric RCT of non-operative management of acute appendicitis; 2) to determine the complication rate of operative v. non-operative management of acute appendicitis in children; 3) to compare health utility and cost of operative v. non-operative management of acute appendicitis in children; and 4) to determine predictors of successful non-operative management. This study capitalizes on the expertise and infrastructures of NIDDK and the Pediatric Emergency Care Applied Research Network (PECARN), and the geographic and patient diversity of PECARN institutions. Patients meeting inclusion criteria will be randomized to either of two arms. Non-operative management patients will be treated with 2 doses of intravenous antibiotics, followed by a 1-week course of oral antibiotics. Patients in the operative arm will undergo laparoscopic appendectomy. The study will require 450 patients per arm (900 total), distributed over 8 investigative sites. The aim of the planning phase of the study (Specific Aim 1) is to optimize the infrastructure and processes need for a multi-center randomized controlled trial, so that subject enrollment can start as early as possible once funding for the clinical study is secured. By the end of the planning phase, the study protocol will be finalized, all sites will be identified, their local personnel updated trained/educated, and a Manual of Operations completed. In close cooperation with NIDDK, a Data Monitoring and Safety Board will be established and its mandate clearly defined. The high incidence of appendicitis in children makes this an important public health topic. This study has the potential to radically alter the treatment of a very common condition, which will have national and international health care repercussions. Additionally, even small advances in health and cost utility, and health care delivery may have far-reaching implications.