RIPASA Treatment Without Operation (TWO) – A Non-Inferiority Prospective Randomised Clinical Controlled Trial of Antibiotic Non-Operative Management Strategy versus Surgery Management Strategy for Early Uncomplicated Acute Appendicitis.
Chee Fui CHONG, Shahriman HUSAIN, Linawati JUMAT, Kim Khee TAN, Samuel KS YAP, Mohammad Ady Adillah AHMAD, Chean Leung CHONG, Amy THIEN, Lian Tat TAN for the RIPASA-TWO trial group.
1Department of General Surgery, 2Department of Accident & Emergency, Raja Isteri Pengiran Anak Saleha Hospital, Bandar Seri Begawan, Brunei Darussalam.
Introduction: The role of an antibiotic non-operative management strategy (AMS) in managing early-uncomplicated acute appendicitis (EUAA) is still debatable and most meta-analysis have not shown significant benefit of AMS over SMS, partly due to variable treatment efficacy, high recurrence rate within a year and a lack of agreement of whom would constitute a group of EUAA. This research proposal provides the framework to investigate the role of AMS versus Surgical Management Strategy (SMS) in patients with clinical diagnosis of EUAA. The primary aim of the study is to compare treatment efficacy of both treatment arms.
Design: A single centre, prospective non-inferiority Randomised Controlled Clinical Trial comparing AMS with SMS in the main tertiary referring hospital in Brunei Darussalam.
Participants and Interventions: Patients aged 13 and above with a clinical diagnosis of EUAA with RIPASA score from 7.5 to 11.5, will be invited to participate in the trial. Once consented, participants will be randomised to either AMS or SMS using a computer-based randomisation allocation programme. Recruitment is planned to start in October 2017 and will recruit 228 patients over a 2 year period. Patients randomised to the AMS arm will receive amikacin IV 1.5mg/kg/day given in 2 doses for 48 hours followed by oral ciprofloxacin 500mg twice daily for 5 days. Patients randomised to SMS will receive standard antibiotics combination of IV cefuroxime 1.5g and metronidazole 500mg three times a day and surgery.
Outcomes: Primary outcome is treatment efficacy within 30 days in each arm and compliance with RIPASA guidelines. Secondary outcomes include length of stay, 30-days treatment related complications, recurrence rate from 1 month up to 1 year, treatment cost, defining effective RIPASA score range for AMS and medical sick leave days taken.
Analysis: Data analysis will be carried out based on intention-to-treat principle combine with per protocol analysis for non-inferiority of AMS arm. Non-inferiority margin is set based on FDA approved 50% reduction of treatment efficacy for AMS arm
Novelty and Significance: The novelty of this research study is that it is the only non-inferiority RCT comparing AMS with SMS that uses a clinical prediction rule (CPR) such as RIPASA Score for clinical diagnosis of EUAA.
The significance of this research study is that it will complete the final and third part of the creation and validation of the RIPASA score as a CPR by assessing its impact on change behavior in managing patients with EUAA with AMS rather than SMS and hence improves patient outcomes by reducing unnecessary negative appendicectomy rate, complications related to undergoing emergency appendicectomy and ultimately reducing cost of managing acute appendicitis surgically.
Keywords: Appendicectomy, Antibiotic Management strategy, Clinical Prediction Rule, Early Uncomplicated Acute Appendicitis, RIPASA Score.
Correspondence: Chee Fui Chong, Consultant, Department of General Surgery, RIPAS Hospital, Bandar Seri Begawan, Brunei Darussalam. E mail: email@example.com
Brunei Int Med J. 2017; 13 (4): 111-123