Mechanical Bowel Preparation and Oral Antibiotics Before Colon Cancer Surgery (COLONPREP)

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

This study aims to demonstrate that a preoperative combination of mechanical bowel preparation and oral antibiotics, before elective laparoscopic colon cancer surgery, is associated with a reduction of postoperative surgical site infection rate, as compared to mechanical bowel preparation alone, oral antibiotics alone, or no colonic preparation.

Our Hypothesis is that a preoperative colonic preparation including a combination of mechanical bowel preparation and oral antibiotics before elective laparoscopic colon cancer surgery is associated with a reduced rate of 30-day postoperative surgical site infection, as compared to mechanical bowel preparation alone, oral antibiotics alone, or no colonic preparation.

Study Overview

• Status: Terminated
• Conditions: Colon Cancer
• Intervention / Treatment: Drug: Sennosides colonic preparation; Drug: Oral Gentamycin; Drug: Oral Ornidazole; Drug: Oral placebo Gentamycin; Drug: Oral placebo Ornidazole

Detailed Description

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 SSI. However, several randomized-controlled trials (RCT) and meta-analyses, have suggested the absence of benefit, in term of postoperative morbidity, of preoperative MBP before elective colon cancer surgery. A meta-analysis of RCT, comparing MBP to no-MBP before elective colon cancer surgery, even suggested that MBP could be associated with an increased SSI rate, as compared to no-MBP. These results led the latest French surgical guidelines of the Société Française de Chirurgie Digestive (SFCD) to recommend the absence of MBP before elective colon cancer surgery.

However, 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. This latter study reported a 50% reduction of SSI rate in the "MBP and oral antibiotics" group, as compared to the "MBP alone" group. Finally, three recent large retrospective registry studies compared the outcomes of four different strategies of preoperative colonic preparation before colorectal surgery: 1) MBP and oral antibiotics, 2) MBP alone, 3) Oral antibiotics alone, and 4) No colonic preparation. However, to date, no RCT has compared the "No preparation" group, which is the gold standard according to the international and French guidelines, to the "MBP and oral antibiotics" group.

The present study is therefore the first double-blinded RCT to compare the SSI rate for 4 types of colonic preparation before elective laparoscopic colonic surgery: 1) MBP and oral antibiotics, 2) MBP alone, 3) Oral antibiotics alone, and 4) No preparation.

• Study Type: Interventional
• Enrollment (Actual): 193
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Clichy, France, 92110
    • Service de chirurgie Colorectale / Hôpital Beaujon

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients aged 18 or more
• Scheduled to undergo elective restorative laparoscopic segmental colectomy for colon cancer
• With Signed consent
• And affiliated to the French social security system

Exclusion Criteria:

• Emergent surgery
• Scheduled total or subtotal colectomy (defined as a colectomy extended from the right colon to a least the left colonic angle)
• Scheduled transverse colectomy
• Scheduled associated proctectomy
• Scheduled associated concomitant resection of another organ (liver, etc.), except the abdominal wall
• Previous segmental colectomy
• Associated inflammatory bowel disease
• Active bacterial infection at the time of surgery or recent antimicrobial therapy (up to 2 weeks before surgery)
• 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1) " MBP and oral antibiotics " group; Sennosides colonic preparation Oral Gentamycin Oral Ornidazole; Sennosides colonic preparation (X-PREP) :1 per day, on day -2 and day -1.; Gentamycin :80 mg, 4 per day, on day -2 and day -1; Liquid forms in individual vials.; Ornidazole :g per day (2 tablet per day), on day -2 and day -1; In tablets.	Drug: Sennosides colonic preparation; Mechanical bowel preparation : Sennosides colonic preparation (X-PREP) 1 per day, on day -2 and day -1; Drug: 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; Sennosides colonic preparation (X-PREP) :1 per day, on day -2 and day -1.; Placebo for oral gentamycin: Same presentation as oral gentamycin x4 per day on day -2 and day -1. - Placebo for oral ornidazole : Same presentation as oral ornidazole 1g per day (2 tablet per day) on day -2 and day -1.	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 tablet per day) on day -2 and day -1
Experimental: 3) " Oral antibiotics alone " group; Oral Gentamycin Oral Ornidazole; Gentamycin :80 mg, 4 per day, on day -2 and day -1; Liquid forms in individual vials.; Ornidazole :g per day (2 tablet per day), on day -2 and day -1; In tablets.	Drug: 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: 4) " No preparation " group; Oral placebo Gentamycin Oral placebo Ornidazole - Placebo for oral gentamycin : Same presentation as oral gentamycin x4 per day on day -2 and day -1 - Placebo for oral ornidazole : Same presentation as oral ornidazole 1g per day (2 tablet 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 tablet 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
Postoperative length of hospital stay	Calculated from the day of surgery to the day of hospital discharge.	Day of hospital discharge
Unplanned hospitalization	Defined as any unplanned hospitalization between surgery and postoperative day 90.	90 days
Tolerance of the colonic preparation	Evaluated using a dedicated tolerance of the colonic preparation questionnaire performed the evening before surgery.	The day before surgery
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
Date of adjuvant chemotherapy beginning	If indicated	During 90 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2018
• Primary Completion (Actual): August 26, 2021
• Study Completion (Actual): March 23, 2022

Study Registration Dates

• First Submitted: March 9, 2018
• First Submitted That Met QC Criteria: March 16, 2018
• First Posted (Actual): March 23, 2018

Study Record Updates

• Last Update Posted (Actual): May 17, 2022
• Last Update Submitted That Met QC Criteria: May 12, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Surgical site infection; Oral antibiotics; Mechanical Bowel Preparation (MBP); Colon cancer surgery
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic 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: P161202J

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