Mechanical Bowel Preparation and Oral Antibiotics Before Rectal Cancer Surgery (PREPACOL2)

Mechanical Bowel Preparation and Oral Antibiotics Before Rectal Cancer Surgery: a Multi Center Double-Blinded Randomized Controlled Trial (PREPACOL2 Study)

This study aims to demonstrate that a preoperative combination of mechanical bowel preparation and oral antibiotics, before elective laparoscopic rectal cancer surgery, is associated with a reduction of postoperative surgical site infection rate, as compared to mechanical bowel preparation alone Our hypothesis is that a preoperative colonic preparation including a combination of mechanical bowel preparation and oral antibiotics before elective laparoscopic rectal cancer surgery is associated with a reduced rate of 30-day postoperative surgical site infection, as compared to mechanical bowel preparation alone

Study Overview

• Status: Completed
• Conditions: Rectal Cancer Surgery
• Intervention / Treatment: Drug: Sennosides colonic preparation; Drug: Oral Gentamycin; Drug: Oral Ornidazole; Drug: Oral Placebo Gentamycin; Drug: Oral Placebo Ornidazole

Detailed Description

This study aims to demonstrate that a preoperative combination of mechanical bowel preparation and oral antibiotics, before elective laparoscopic rectal cancer surgery, is associated with a reduction of postoperative surgical site infection rate, as compared to mechanical bowel preparation alone.

This study's hypothesis is that a preoperative colonic preparation including a combination of mechanical bowel preparation and oral antibiotics before elective laparoscopic rectal cancer surgery is associated with a reduced rate of 30-day postoperative surgical site infection, as compared to mechanical bowel preparation alone Preoperative mechanical bowel preparation (MBP) has been proposed in an attempt to reduce the colonic fecal load and to limit the risk of surgical site contamination, thus theoretically limiting the risk of postoperative surgical site infection (SSI). However, the benefit of such MBP before colorectal surgery is related to type of procedure performed. Indeed, several randomized controlled trials (RCT) and meta-analyses have demonstrated the absence of benefit of MBP before colon cancer surgery, whereas a recent RCT suggested that MBP before rectal cancer surgery was associated to a significant reduction of postoperative SSI, as compare to the absence of preoperative MBP.

Recent studies suggested that the adjunction of oral antibiotics during MBP could help efficiently reduce the risk of postoperative SSI. Indeed, a recent meta-analysis of RCT have suggested that patients preoperatively receiving both MBP and oral antibiotics were exposed to a significantly reduced risk of postoperative SSI, as compared to patients receiving only preoperative MBP. This result was confirmed in a recent RCT which compared preoperative MBP and oral antibiotics versus MBP alone in a heterogeneous population of patients who underwent laparoscopic colonic or rectal surgery. However, to date, no RCT compared the outcomes of an MBP with oral antibiotics to MBP without oral antibiotics in a homogeneous cohort of patients undergoing rectal cancer surgery.

This study aims to demonstrate that a preoperative combination of mechanical bowel preparation and oral antibiotics, before elective laparoscopic rectal cancer surgery, is associated with a reduction of postoperative surgical site infection rate, as compared to mechanical bowel preparation alone.

• Study Type: Interventional
• Enrollment (Actual): 414
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yves PANIS, MD, Phd; Phone Number: 33 (0)1 40 87 45 47; Email: yves.panis@aphp.fr
• Study Contact Backup: Name: Massimo GIACCA, MD; Email: massimo.giacca@aphp.fr

Study Locations

• France
  • Ile De France
    • Paris, Ile De France, France, 75010
      • Service de chirurgie viscérale, cancérologique / Hôpital Saint-Louis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged 18 or more
• Scheduled to undergo elective restorative laparoscopic cancer of the rectal (<15 cm from the anal margin) with sphincter preservation
• With Signed consent
• And affiliated to the French social security system

Exclusion Criteria:

• Emergent surgery
• Scheduled total colo-proctectomy
• Scheduled abdominoperineal restion with definitive colostomy
• Scheduled associated concomitant resection of another organ (liver, etc.)
• Active bacterial infection at the time of surgery or recent antibiotic therapy (up to 15 days before surgery)
• Associated inflammatory bowel disease
• Patients with known colonization with multidrug-resistant enterobacteriacea
• History of allergy or contraindication to the Ornidazole, Gentamycin, X-PREP or to any of the excipients of the drugs used.
• Cirrhosis of grade B and C (Child-Pugh classification)
• Myasthenia
• Allergy to one of the other treatments administered for the purpose of the trial (including betadine)
• Patient suffering from severe central neurologic diseases, fixed or progressive.
• Pregnant patients
• Refusal to participate or inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1) " MBP and oral antibiotics " group; Sennosides colonic preparation Oral Gentamycin Oral Ornidazole	Drug: Sennosides colonic preparation; Mechanical bowel preparation : Sennosides colonic preparation (X-PREP) 1 per day, on day -2 and day -1; Drug: Oral Gentamycin; Oral gentamycin: Gentamycin 80 mg, 4 per day, on day -2 and day -1; Liquid forms in individual vials; Drug: Oral Ornidazole; Oral ornidazole : Ornidazole 1 g per day (2 tablet per day), on day -2 and day -1; In tablets
Placebo Comparator: 2) " MBP alone " group; Sennosides colonic preparation Oral placebo Gentamycin Oral placebo Ornidazole	Drug: Sennosides colonic preparation; Mechanical bowel preparation : Sennosides colonic preparation (X-PREP) 1 per day, on day -2 and day -1; Drug: Oral Placebo Gentamycin; Placebo for oral gentamycin : Same presentation as oral gentamycin x4 per day on day -2 and day -1; Drug: Oral Placebo Ornidazole; Placebo for oral ornidazole : Same presentation as oral ornidazole 1g per day (2 tablets per day) on day -2 and day -1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative 30-day surgical site infection (SSI).	SSI will be defined and classified as superficial, deep and/or organ-space infection on the basis of validated and well-defined criteria developed by the Centers for Disease Control and Prevention (CDC), validated in French by the Comité technique des infections nosocomiales et des infections liées aux soins.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall postoperative morbidity	Including all postoperative complications occurring within 30 days after surgery, defined and classified according to the Clavien-Dindo classification.	30 days
Severe postoperative morbidity	Including all complications graded 3 or more according to the Clavien-Dindo classification, and occurring within 30 days after surgery.	30 days
Postoperative mortality	Including all deaths occurring within 30 days after surgery.	30 days
Postoperative anastomotic leakage	Defined as the passing of any intra-colonic content (air, liquid, intestinal content, or radiological contrast) through an anastomosis or by an peri-anastomotic abscess, even in the absence of intra-colonic content leak through the anastomosis, observed in drainages, surgical incision, vagina, during a surgical procedure or on a radiological examination, occurring within 90 days after surgery.	90 days
Unplanned hospitalization	Defined as any unplanned hospitalization between surgery and postoperative day 90.	90 days
Clostridium difficile colitis occurrence	Defined as clinical symptoms of clostridium difficile colitis with at least 1 stool sample positive for Clostridium difficile toxin A/B as detected by enzyme-linked immunosorbent assay within 30 days after surgery.	30 days
Rate of multi-resistant bacteria carriage	Defined as rate of multi-resistant bacteria carriage	The day before or the day of surgery
Postoperative length of hospital stay	Calculated from the day of surgery to the day of hospital discharge.	Up to 90 days
Tolerance of the colonic preparation	Evaluated using a dedicated questionnaire performed the evening before surgery.	The day before surgery
Date of adjuvant chemotherapy beginning	If indicated	90 days
Temporary stoma closure rate	Define as temporary stoma closure	90 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2018
• Primary Completion (Actual): October 23, 2023
• Study Completion (Actual): December 12, 2023

Study Registration Dates

• First Submitted: March 9, 2018
• First Submitted That Met QC Criteria: April 6, 2018
• First Posted (Actual): April 9, 2018

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Surgical site infection; Oral antibiotics; Mechanical Bowel Preparation (MBP); Rectal cancer surgery
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Laxatives; Antitrichomonal Agents; Gentamicins; Sennosides; Ornidazole
• Other Study ID Numbers: P160938J

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan to make IPD available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No