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

Abstract

Introduction: Despite 40 randomised controlled trials (RCTs) investigating preoperative oral antibiotics (OA) and mechanical bowel preparation (MBP) to reduce surgical site infection (SSI) rate following colon surgery, there has never been an RCT published comparing OA alone versus no preparation. Of the four possible regimens (OA alone, MBP alone, OA plus MBP and no preparation), randomised evidence is conflicting for studied groups. Furthermore, guidelines vary, with recommendations for OA alone, OA plus MBP or no preparation. The National Surgical Quality Improvement Program (NSQIP) has automated data collection for surgical patients. Similarly, the 'REthinking Clinical Trials' (REaCT) platform increases RCT enrolment by simplifying pragmatic trial design. In this novel RCT protocol, we combine REaCT and NSQIP to compare OA alone versus no preparation for SSI rate reduction in elective colon surgery. To our knowledge, this is the first published RCT protocol that leverages NSQIP for data collection. In our feasibility study, 67 of 74 eligible patients (90%) were enrolled and 63 of 67 (94%) were adherent to protocol. The 'REaCT-NSQIP' trial design has great potential to efficiently generate level I evidence for other perioperative interventions.

Methods and analysis: SSI rates following elective colorectal surgery after preoperative OA or no preparation will be compared. We predict 45% relative rate reduction of SSI, improvement in length of stay, reduced costs and increased quality of life, with similar antibiotic-related complications. Consent, using the 'integrated consent model', and randomisation on a mobile device are completed by the surgeon in a single clinical encounter. Data collection for the primary end point is automatic through NSQIP. Analysis of cost per weighted case, cost utility and quality-adjusted life years will be done.

Ethics and dissemination: This study is approved by The Ontario Cancer Research Ethics Board. Results will be disseminated in surgical conferences and peer-reviewed journals.

Trial registration number: NCT03663504; Pre-results, recruitment phase.

Keywords: clinical trials; colorectal surgery; infection control; statistics & research methods; wound management.

Figure 1

The REaCT platform has been highly successful over the past 5 years, with 15 completed or ongoing pragmatic trials and over 2500 patients enrolled to date (April 2020). NSQIP, National Surgical Quality Improvement Program; REaCT, REthinking Clinical Trials.

Figure 2

Cumulative total of eligible versus enrolled patients in the 8-month, single centred, REaCT–NSQIP feasibility trial. In our pilot feasibility trial at The Ottawa Hospital, we enrolled 67 patients over 8 months, out of a total of 74 eligible patients (>90% enrolment rate). Adherence to preoperative OA as per protocol was 94%. NSQIP, National Surgical Quality Improvement Program; OA, oral antibiotics; RCT, randomised controlled trial; REaCT, REthinking Clinical Trials.

Figure 3

REaCT–NSQIP trial enrolment flow chart highlighting the integrated oral consent, web-based randomisation and automatic data collection through NSQIP–ERAS. *Adapted from Hilton et al. ERAS, Enhanced Recovery After Surgery; LOS, length of stay; NSQIP, National Surgical Quality Improvement Program; QoL, quality of life; REaCT, REthinking Clinical Trials; SSI, surgical site infection.

Figure 4

The REaCT–NSQIP single-centred feasibility study was completed in Q2 2019. Given that the statistical power of the study is dependent on the baseline SSI rate across participating sites, the SSI rate of the NSQIP-ON Collaborative (which includes >40 hospitals in the trial region of Ontario) will be reassessed at the midpoint of trial enrolment (≈Q3 2021), allowing for adjustment of the final sample size. NSQIP, National Surgical Quality Improvement Program; REaCT, REthinking Clinical Trials; SSI, surgical site infection.