Classical trial design is too costly and inefficient to effectively evaluate perioperative interventions. Furthermore, classical trials rarely include patients from rural or community hospitals, where >50% of surgery is performed. This institutional enrolment bias not only reduces opportunities for patients from regional hospitals to participate in clinical trials, but also limits generalizability of results and restricts knowledge translation to academic centres. To address these issues, we have combined the highly successful REthinking Clinical Trials (REaCT) platform with automatic data collection by the National Surgical Quality Improvement Program (NSQIP), and packaged it into a fully decentralized, remotely managed clinical trial. By investigating the effect of a simple, low-cost intervention (oral antibiotics prior to colectomy) on a high-impact outcome (surgical site infection), we have demonstrated the remarkable potential of the REaCT-NSQIP-Remote (RNR) platform to change the way randomised surgical trials are performed across Canada.

Surgical site infections (SSIs) after colectomy are frequent, serious, and costly. Over 20,000 colon surgeries are performed every year in Canada, with 50-75% of these patients served in community hospitals. Up to 15% will suffer surgical site infections, resulting in significant morbidity and excess cost. Despite over 40 randomized trials investigating the role of preoperative oral antibiotics (OA) and bowel preparation for SSI prevention after colon surgery, controversy remains. The RNR-OA trial is the first to assess if a one-day course of preoperative oral neomycin & metronidazole without bowel preparation reduces surgical site infections after colectomy versus no oral antibiotics. Based on previous data, we expect a 45% reduction in SSIs with oral antibiotics. Thus, the RNR trial has the potential for high impact on patient care using a cheap, readily available intervention, thereby dramatically reducing healthcare system costs. To date, our group has completed a successful single-centre pilot study over an 8-month period, demonstrating unprecedented enrollment of 67 of 74 eligible patients (90%), with 94% protocol compliance, and remarkably 100% NSQIP automatic data capture (effectively zero loss to follow up). We built on this success, by obtaining supplementary peer-reviewed funding through the CIHR/NSERC/NMHRC ‘New Frontiers in Research Fund for Innovative Approaches to the Pandemic’ for the remotely-managed RNR trial platform. Now, with 334 patients currently enrolled and 4 remotely managed trial sites, we are poised to complete recruitment in 2023, with results in 2024. Most importantly, the RNR-OA trial will demonstrate the feasibility of the RNR platform as a means to rapidly produce highly generalizable level-I evidence for perioperative interventions. With the success of the RNR-OA trial, we will establish a nationwide infrastructure of NSQIP trial sites to execute turnkey, streamlined, cost-effective pragmatic randomised trials to answer practice changing quality improvement questions to benefit all Canadians.

Apte SS et al. (Auer RC) – Prospective randomised controlled trial using the REthinking Clinical Trials (REaCT) platform and National Surgical Quality Improvement Program (NSQIP) to compare no preparation versus preoperative oral antibiotics alone for surgical site infection rates in elective colon surgery: a protocol. BMJ Open. 2020 Jul 9; 10(07):e036866
https://pubmed.ncbi.nlm.nih.gov/32647023/
DOI: 10.1136/bmjopen-2020-036866