Ignite Creation Date:
2025-12-25 @ 4:18 AM
Ignite Modification Date:
2026-02-24 @ 8:26 AM
Study NCT ID:
NCT02618720
Status:
COMPLETED
Last Update Posted:
2022-07-07
First Post:
2015-11-05
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Intravenous Versus Combined Oral and Intravenous Antimicrobial Prophylaxis for the Prevention of Surgical Site Infection in Elective Colorectal Surgery
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D013530', 'term': 'Surgical Wound Infection'}], 'ancestors': [{'id': 'D014946', 'term': 'Wound Infection'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D011183', 'term': 'Postoperative Complications'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D009950', 'term': 'Ornidazole'}], 'ancestors': [{'id': 'D009593', 'term': 'Nitroimidazoles'}, {'id': 'D009574', 'term': 'Nitro Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 920}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2016-05-25', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-07', 'completionDateStruct': {'date': '2020-06-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-07-04', 'studyFirstSubmitDate': '2015-11-05', 'studyFirstSubmitQcDate': '2015-11-27', 'lastUpdatePostDateStruct': {'date': '2022-07-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2015-12-01', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2019-11-26', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'occurrence of any SSI within 30 days after surgery.', 'timeFrame': '30 days after surgery', 'description': 'The primary end point of the trial is the occurrence of any SSI within 30 days after surgery. SSI will be classified as superficial, deep and/or organ-space infection according to validated and well-defined criteria developed by the Centers for Disease Control and Prevention (CDC).'}], 'secondaryOutcomes': [{'measure': 'Incidence of individual types of SSI according to the group of treatment', 'timeFrame': '30 days after surgery', 'description': 'Incidence of individual types of SSI (superficial incision infection, deep incision infection and organ-space infection) according to the group of treatment, 30 days after surgery'}, {'measure': 'Number of postoperative complications', 'timeFrame': '30 days after surgery', 'description': 'Using the Dindo and Clavien classification'}, {'measure': 'Number of surgical complications: anastomotic leakage and the need for abdominal reoperation and/or radiological intervention', 'timeFrame': '30 days after surgery'}, {'measure': 'Duration of hospital stay', 'timeFrame': '30 days after surgery', 'description': 'Including hospital stay of patients who are readmitted after surgery'}, {'measure': 'All-cause mortality', 'timeFrame': '30 days after surgery'}, {'measure': 'All-cause mortality', 'timeFrame': '90 days after surgery'}, {'measure': 'Time to introduction of adjuvant chemotherapy related to SSI', 'timeFrame': '30 days after surgery'}, {'measure': 'Postoperative syndrome of systemic inflammatory response (Infectious complications)', 'timeFrame': '30 days after surgery', 'description': 'Number of Postoperative syndrome of systemic inflammatory responses, in each group'}, {'measure': 'Sepsis (Infectious complications)', 'timeFrame': '30 days after surgery', 'description': 'Number of Sepsis, in each group'}, {'measure': 'Septic shock (Infectious complications)', 'timeFrame': '30 days after surgery', 'description': 'Number of Septic shocks, in each group'}, {'measure': 'Arrhythmia (Cardiovascular complications)', 'timeFrame': '30 days after surgery', 'description': 'Number of arrhythmias, in each group'}, {'measure': 'Myocardial infarction (Cardiovascular complications)', 'timeFrame': '30 days after surgery', 'description': 'Number of myocardial infarctions, in each group'}, {'measure': 'Acute cardiac failure (Cardiovascular complications)', 'timeFrame': '30 days after surgery', 'description': 'Number of acute cardiac failures, in each group'}, {'measure': 'Pneumonia (Respiratory complications)', 'timeFrame': '30 days after surgery', 'description': 'Number of pneumonias, in each group'}, {'measure': 'Need for postoperative reventilation (Respiratory complications)', 'timeFrame': '30 days after surgery', 'description': 'Number of postoperative reventilations (intubation and/or non-invasive mechanical ventilation), in each group'}, {'measure': 'Renal dysfunction', 'timeFrame': '30 days after surgery', 'description': 'Number of Renal dysfunctions in each group. Defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) classification'}, {'measure': 'Time to initiation of adjuvant chemotherapy', 'timeFrame': '30 days after surgery', 'description': 'Comparaison of time to initiation of adjuvant chemotherapy between the 2 groups'}, {'measure': 'Need for hospital readmission', 'timeFrame': '30 days after surgery', 'description': 'Number of hospital readmissions, in each group'}, {'measure': 'Unexpected admission to intensive care unit', 'timeFrame': '30 days after surgery', 'description': 'Number of Unexpected admissions to intensive care unit, in each group'}, {'measure': 'Hospital free days', 'timeFrame': '30 days after surgery'}]}, 'conditionsModule': {'keywords': ['Antimicrobial prophylaxis', 'Colorectal surgery', 'Surgical Site Infection', 'Postoperative morbidity'], 'conditions': ['Elective Colorectal Surgery']}, 'referencesModule': {'references': [{'pmid': '36748942', 'type': 'DERIVED', 'citation': 'Willis MA, Toews I, Soltau SL, Kalff JC, Meerpohl JJ, Vilz TO. Preoperative combined mechanical and oral antibiotic bowel preparation for preventing complications in elective colorectal surgery. Cochrane Database Syst Rev. 2023 Feb 7;2(2):CD014909. doi: 10.1002/14651858.CD014909.pub2.'}, {'pmid': '36328372', 'type': 'DERIVED', 'citation': 'Futier E, Jaber S, Garot M, Vignaud M, Panis Y, Slim K, Lucet JC, Lebuffe G, Ouattara A, El Amine Y, Couderc P, Dupre A, De Jong A, Lasocki S, Leone M, Pottecher J, Pereira B, Paugam-Burtz C; COMBINE study group. Effect of oral antimicrobial prophylaxis on surgical site infection after elective colorectal surgery: multicentre, randomised, double blind, placebo controlled trial. BMJ. 2022 Nov 3;379:e071476. doi: 10.1136/bmj-2022-071476.'}, {'pmid': '29654027', 'type': 'DERIVED', 'citation': 'Vignaud M, Paugam-Burtz C, Garot M, Jaber S, Slim K, Panis Y, Lucet JC, Bourdier J, Morand D, Pereira B, Futier E; COMBINE trial management committee. Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial. BMJ Open. 2018 Apr 12;8(4):e020254. doi: 10.1136/bmjopen-2017-020254.'}]}, 'descriptionModule': {'briefSummary': 'To assess the effects of a combined antimicrobial prophylaxis using oral ornidazole (the day before surgery) and intravenous cephalosporin (before surgical incision) with that of intravenous cephalosporin alone (standard of care) in combination with oral placebo on the incidence of SSI within 30 days after elective colorectal surgery.', 'detailedDescription': 'Surgical site infection (SSI) is a major cause of nosocomial infection in surgical patients, with the highest rates being reported (ranging from 15% to 30%) in colorectal surgery. SSI is an independent predictor of postoperative mortality and is associated with longer hospital stay, a 5-fold likelihood of postoperative readmission and a 2- to 3-fold increase in costs of care. Given the high prevalence and financial burden associated with SSI, American and European guidelines have been issued providing evidenced-based recommendations for the prevention of postoperative SSI. However, the prevalence of SSI remains high despite adherence to these guidelines and the application of evidence-based preventive measures.\n\nRisk factors for SSI, whether modifiable or not, are mainly related to the patient condition (including age, severe comorbidity, diabetes, nutritional status, steroid use, smoking, and immunosuppression) and/or the surgical procedure (especially the surgical duration and skin disinfection). The prevention of SSI consists of several individual measures, and antibiotic prophylaxis covering aerobic and anaerobic bacteria is highly recommended in patients scheduled to elective colorectal resection, with French and European guidelines recommending the administration of intravenous cephalosporin within 30 minutes before surgical incision.\n\nRecent data from retrospective studies and two meta-analyses of clinical trials provided compelling arguments that oral antibiotic administration before surgery in addition to conventional intravenous prophylaxis may be useful in further reducing by almost 75% the incidence of SSI (relative risk 0.55 \\[CI95%: 0.41 to 0.74\\]) after elective colorectal cancer surgery.\n\nHowever, most of these studies have limitations precluding extrapolation of data into routine care, especially:\n\n1. prolonged duration of intravenous antibiotic administration, which is no longer recommended in elective surgery;\n2. the use of antibiotics for oral prophylaxis whose availability is limited;\n3. only a few studies focused specifically on colorectal resection;\n4. most studies did not include enhanced recovery after surgery (ERAS) programs, which was found to improve outcome following colorectal surgery, and\n5. most studies have used mechanical bowel preparation, which is no longer recommended in colonic surgery while the issue still remains open for rectal surgery.\n\nInvestigators hypothesized that oral antibiotic prophylaxis using ornidazole, which has a spectrum of activity extended to most anaerobic bacteria and whose pharmacokinetic profile allows a single administration the day before surgery, in addition to intravenous antibiotic prophylaxis could be more effective than intravenous antibiotic prophylaxis alone using cephalosporin in reducing the incidence of SSI after elective colorectal surgery. Given the number of patients operated of colorectal surgery each year, the study is of significant clinical importance'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age \\> 18\n* Laparoscopic or non-laparoscopic elective colorectal surgery\n\nExclusion Criteria:\n\n* Non elective colorectal surgery (emergent surgery and/or reintervention or revision of a previous colorectal procedure)\n* Significant concomitant surgical procedure (e.g., liver resection for metastasis)\n* Bacterial infection at the time of surgery or antimicrobial therapy up to 2 weeks before surgery\n* Inflammatory bowel disease\n* Severe obesity (defined as a BMI \\>35 kg/m2)\n* Known history of hypersensitivity to β-lactams and imidazoles\n* Preoperative severe impairment in renal function (creatinine clearance (MDRD) \\< 30 ml/min)\n* Patients with known colonization with multidrug-resistant digestive bacteria, especially multidrug-resistant gram-negative bacteria (requiring specific infection control measures)\n* Allergy to lactose, galactose intolerance, Lapp lactase deficiency or glucose/galactose malabsorption (rare metabolic disease)\n* Pregnant women, breastfeeding women, women of childbearing age without effective contraceptive- Refusal to participate or inability to provide informed consent'}, 'identificationModule': {'nctId': 'NCT02618720', 'acronym': 'COMBINE', 'briefTitle': 'Intravenous Versus Combined Oral and Intravenous Antimicrobial Prophylaxis for the Prevention of Surgical Site Infection in Elective Colorectal Surgery', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Clermont-Ferrand'}, 'officialTitle': 'Intravenous Versus Combined Oral and Intravenous Antimicrobial Prophylaxis for the Prevention of Surgical Site Infection in Elective Colorectal Surgery: A Double-blinded Multicenter Prospective Randomized Controlled Trial', 'orgStudyIdInfo': {'id': 'CHU-0250'}, 'secondaryIdInfos': [{'id': '2015-002559-84', 'type': 'REGISTRY', 'domain': '2015-002559-84'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'ornidazole', 'description': 'oral antibiotic prophylaxis using ornidazole, which has a spectrum of activity extended to most anaerobic bacteria and whose pharmacokinetic profile allows a single administration the day before surgery, in addition to intravenous antibiotic prophylaxis could be more effective than intravenous antibiotic prophylaxis alone using cephalosporin in reducing the incidence of SSI after elective colorectal surgery. Given the number of patients operated of colorectal surgery each year, the study is of significant clinical importance', 'interventionNames': ['Drug: ornidazole']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'placebo', 'description': 'oral antibiotic prophylaxis using ornidazole, which has a spectrum of activity extended to most anaerobic bacteria and whose pharmacokinetic profile allows a single administration the day before surgery, in addition to intravenous antibiotic prophylaxis could be more effective than intravenous antibiotic prophylaxis alone using cephalosporin in reducing the incidence of SSI after elective colorectal surgery. Given the number of patients operated of colorectal surgery each year, the study is of significant clinical importance', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'ornidazole', 'type': 'DRUG', 'armGroupLabels': ['ornidazole']}, {'name': 'Placebo', 'type': 'DRUG', 'armGroupLabels': ['placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '63003', 'city': 'Clermont-Ferrand', 'country': 'France', 'facility': 'CHU Clermont-Ferrand', 'geoPoint': {'lat': 45.77969, 'lon': 3.08682}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Clermont-Ferrand', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}