Mechanical Bowel Preparation and Oral Antibiotics Before Colon Cancer Surgery

Phase 3

Terminated

• Conditions: Colon Cancer
• Interventions: Drug: Sennosides colonic preparation; Drug: Oral placebo Gentamycin; Drug: Oral Gentamycin; Drug: Oral placebo Ornidazole; Drug: Oral Ornidazole

• Registration Number: NCT03475680
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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.

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 Timeline

• Study First Submitted: 2018-03-09
• Study First Submitted QC: 2018-03-16
• Study First Posted: 2018-03-23
• Study Start: 2018-08-08
• Primary Completion: 2021-08-26
• Study Completion: 2022-03-23
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-12
• Last Update Posted: 2022-05-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 193

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1) " MBP and oral antibiotics " group	Sennosides colonic preparation	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 : 1. g per day (2 tablet per day), on day -2 and day -1; In tablets.
1) " MBP and oral antibiotics " group	Oral Ornidazole	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 : 1. g per day (2 tablet per day), on day -2 and day -1; In tablets.
1) " MBP and oral antibiotics " group	Oral Gentamycin	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 : 1. g per day (2 tablet per day), on day -2 and day -1; In tablets.
2) " MBP alone " group	Sennosides colonic preparation	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.
4) " No preparation " group	Oral placebo Ornidazole	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
3) " Oral antibiotics alone " group	Oral Gentamycin	Oral Gentamycin Oral Ornidazole * Gentamycin : 80 mg, 4 per day, on day -2 and day -1; Liquid forms in individual vials. * Ornidazole : 1. g per day (2 tablet per day), on day -2 and day -1; In tablets.
4) " No preparation " group	Oral placebo Gentamycin	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
2) " MBP alone " group	Oral placebo Gentamycin	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.
2) " MBP alone " group	Oral placebo Ornidazole	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.
3) " Oral antibiotics alone " group	Oral Ornidazole	Oral Gentamycin Oral Ornidazole * Gentamycin : 80 mg, 4 per day, on day -2 and day -1; Liquid forms in individual vials. * Ornidazole : 1. g per day (2 tablet per day), on day -2 and day -1; In tablets.

Primary Outcome Measures

Name	Time	Method
Postoperative 30-day surgical site infection (SSI).	30 days	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

Secondary Outcome Measures

Name	Time	Method
Tolerance of the colonic preparation	The day before surgery	Evaluated using a dedicated tolerance of the colonic preparation questionnaire performed the evening before surgery.
Rate of multi-resistant bacteria carriage	The day before or the day of surgery	Defined as rate of multi-resistant bacteria carriage
Severe postoperative morbidity	30 days	Including all complications graded 3 or more according to the Clavien-Dindo classification, and occurring within 30 days after surgery.
Clostridium difficile colitis occurrence	30 days	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.
Postoperative length of hospital stay	Day of hospital discharge	Calculated from the day of surgery to the day of hospital discharge.
Unplanned hospitalization	90 days	Defined as any unplanned hospitalization between surgery and postoperative day 90.
Date of adjuvant chemotherapy beginning	During 90 days	If indicated
Overall postoperative morbidity	30 days	Including all postoperative complications occurring within 30 days after surgery, defined and classified according to the Clavien-Dindo classification.
Postoperative mortality	30 days	Including all deaths occurring within 30 days after surgery.
Postoperative anastomotic leakage	90 days	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.

Trial Locations

Locations (1)

Service de chirurgie Colorectale / Hôpital Beaujon; 🇫🇷 Clichy, France