COMBINE.

Study name	Intravenous Versus Combined Oral and Intravenous Antimicrobial Prophylaxis for the Prevention of Surgical Site Infection in Elective Colorectal Surgery
Methods	Study type: interventional Study design Allocation: randomised Intervention model: parallel assignment Masking: double (participant, investigator) Primary purpose: prevention
Participants	Condition or disease: elective colorectal surgery Inclusion criteria Age > 18 Laparoscopic or non‐laparoscopic elective colorectal surgery Exclusion criteria Non elective colorectal surgery (emergent surgery and/or re‐intervention or revision of a previous colorectal procedure) Significant concomitant surgical procedure (e.g. liver resection for metastasis) Bacterial infection at the time of surgery or antimicrobial therapy up to 2 weeks before surgery Inflammatory bowel disease Severe obesity (defined as a BMI >35 kg/m2) Known history of hypersensitivity to β‐lactams and imidazoles Preoperative severe impairment in renal function (creatinine clearance (MDRD) < 30 ml/min) Patients with known colonisation with multidrug‐resistant digestive bacteria, especially multidrug‐resistant gram‐negative bacteria (requiring specific infection control measures) Allergy to lactose, galactose intolerance, Lapp lactase deficiency or glucose/galactose malabsorption (rare metabolic disease) Pregnant women, breastfeeding women, women of childbearing age without effective contraceptive‐ Refusal to participate or inability to provide informed consent Target sample size: ‐ Actual Enrolment: 920
Interventions	Treatment arms Combined oral and intravenous antimicrobial prophylaxis (intervention group): patients will receive a single oral dose of 1g ornidazole at 12hours before surgery in combination with intravenous dose of 2g cefoxitin at least 30min before surgical incision Intravenous antimicrobial prophylaxis (control group): patients will receive a single oral dose of placebo at 12hours before surgery in combination with intravenous dose of 2g cefoxitin at least 30 minutes before surgical incision In each group, an additional dose of 1g cefoxitin will be given every 2hours during surgery. After surgery, no additional antibiotic doses will be given to either of the groups. Patients will be able to receive oral laxative (1 or 2 packages of X‐PREP powder diluted in a glass of water) and retrograde rectal enema the day before surgery, as used previously.
Outcomes	Primary outcome: Occurrence of any SSI within 30 days after surgery. [Time Frame: 30 days after surgery] Secondary outcome: Incidence of individual types of SSI according to the group of treatment Number of treatment‐related adverse events with the combined oral and intravenous antimicrobial prophylaxis Number of postoperative complications Number of surgical re‐intervention Number of duration of hospital stay Number of postoperative mortality related to SSI Time to introduction of adjuvant chemotherapy related to SSI
Starting date	Date of registration: November 5, 2015 Study Start Date: May 25, 2016 Actual Study Completion Date: June 30, 2020 Recruitment Status: Completed
Contact information	Contact person: Professor Emmanuel Futier Affiliation: University Hospital, Clermont‐Ferrand Country of origin: France
Notes	Ethics approval: COMBINE trial has been approved by an independent ethics committee for all study centres Source of funding: COMBINE trial is supported by funding from French Ministry of Health (Programme Hospitalier de Recherché Clinique (PHRC) National 2014) and from the University Hospital of Clermont‐Ferrand