Prevention of severe infectious complications after colorectal surgery using preoperative orally administered antibiotic prophylaxis (PreCaution): study protocol for a randomized controlled trial

Abstract

BackgroundColorectal surgery is frequently complicated by surgical site infections (SSIs). The most important consequences of SSIs are prolonged hospitalization, an increased risk of surgical reintervention and an increase in mortality. Perioperative intravenously administered antibiotic prophylaxis is the standard of care to reduce the risk of SSIs. In the last few decades, preoperative orally administered antibiotics have been suggested as additional prophylaxis to further reduce the risk of infection, but are currently not part of routine practice in most hospitals. The objective of this study is to evaluate the efficacy of a preoperative orally administered antibiotic prophylaxis (Pre-OP) in addition to intravenously administered perioperative antibiotic prophylaxis to reduce the incidence of deep SSIs and/or mortality after elective colorectal surgery.Methods/designThe PreCaution trial is designed as a multicenter, double-blind, randomized, placebo-controlled clinical trial that will be carried out in The Netherlands. Adult patients who are scheduled for elective colorectal surgery are eligible to participate. In total, 966 patients will be randomized to receive the study medication. This will either be Pre-OP, a solution that consists of tobramycin and colistin sulphate, or a placebo solution. The study medication will be administered four times daily during the 3 days prior to surgery. Perioperative intravenously administered antibiotic prophylaxis will be administered to all patients in accordance with national infection control guidelines. The primary endpoint of the study is the cumulative incidence of deep SSIs and/or mortality within 30 days after surgery. Secondary endpoints include both infectious and non-infectious complications of colorectal surgery, and will be evaluated 30 days and/or 6 months after surgery.DiscussionTo date, conclusive evidence on the added value of preoperative orally administered antibiotic prophylaxis in colorectal surgery is lacking. The PreCaution trial should determine the effects of orally administered antibiotics in preventing infectious complications in elective colorectal surgery.Trial registrationNetherlands Trial Register, ID: NTR6113. Registered on 11 October 2016; EudraCT 2015-005736-17.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-018-2439-4) contains supplementary material, which is available to authorized users.

Prevention of severe infectious complications after colorectal surgery using oral non-absorbable antimicrobial prophylaxis: results of a multicenter randomized placebo-controlled clinical trial

“…The predictive power for the planned sample size given the observed results (that is, the probability of having a significant result at the end of the study, was for it to be completed, given the observed results in the 78 patients) was 67%. Due to insufficient power, we were unable to perform any of the preplanned subgroup analyses [15].…”

“…An in-depth description of the rationale and methods was published previously [15]. The trial is registered in the Netherlands Trial Register under NL5932.…”

“…The study was designed as a double-blind placebocontrolled randomized trial and was conducted from April 2017 through August 2018 in six Dutch hospitals. (Supplementary Table 1) Patients who were scheduled for colorectal surgery and who had no absolute contraindication for the study medication [15] were eligible to participate. Written informed consent was obtained from all participants.…”

“…Definitions of all outcomes are summarized in Fig. 1 and were described in more detail in the trial protocol [15]. The primary outcome was deep SSI and/or mortality in the 30 days after surgery.…”

The use of oral antibiotics and mechanical bowel preparation in elective colorectal resection for the reduction of surgical site infection

“…In the Netherlands, a cohort study assessing OAB alone as standard of care over time was able to demonstrate a 6.2% reduction in deep SSI and/or mortality, which equated to a 42% risk reduction . The authors question the benefit of MBP in addition to OAB and are running the PreCaution study to assess whether use of OAB alone is sufficient .…”