Mechanical Bowel Preparation and Oral Antibiotics Before Rectal Cancer Surgery

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Rectal Cancer Surgery

Intervention / Treatment
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* Drug: Sennosides colonic preparation
* Drug: Oral Gentamycin
* Drug: Oral Ornidazole
* Drug: Oral Placebo Gentamycin
* Drug: Oral Placebo Ornidazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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. | Up to 90 days | 
| Unplanned hospitalization | Defined as any unplanned hospitalization between surgery and postoperative day 90. | 90 days | 
| Tolerance of the colonic preparation | Evaluated using a dedicated 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 | 90 days | 
| Temporary stoma closure rate | Define as temporary stoma closure | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mechanical Bowel Preparation (MBP), Oral antibiotics, Rectal cancer surgery, Surgical site infection