Ignite Creation Date:
2025-12-24 @ 2:40 PM
Ignite Modification Date:
2026-02-03 @ 3:26 PM
Study NCT ID:
NCT02445859
Status:
COMPLETED
Last Update Posted:
2019-10-10
First Post:
2015-05-13
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Continuous Antibiotic Prophylaxis in Colorectal Surgery
Sponsor:
Organization:
Raw JSON
{'hasResults': True, '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'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'a.kirby@leeds.ac.uk', 'phone': '0044 113 3923989', 'title': 'Andrew Kirby', 'organization': 'The Universit yof Leeds'}, 'certainAgreement': {'piSponsorEmployee': True}, 'limitationsAndCaveats': {'description': 'These patients are expected to have multiple adverse events. We only formally collected all serious adverse events, plus specific events e.g. C.difficile. As a pilot trial we have learned about the collection of adverse events in this patient group.'}}, 'adverseEventsModule': {'timeFrame': '30 days', 'eventGroups': [{'id': 'EG000', 'title': 'Standard Regimen', 'description': 'Cefuroxime 1.5grams pre-operatively Repeated every 4 hours\n\nCefuroxime bolus-continuous infusion: Cefuroxime 1.5 grams pre-operatively, repeated 4 hourly during surgery.', 'otherNumAtRisk': 43, 'deathsNumAtRisk': 43, 'otherNumAffected': 0, 'seriousNumAtRisk': 43, 'deathsNumAffected': 0, 'seriousNumAffected': 3}, {'id': 'EG001', 'title': 'Interventional Regimen', 'description': 'Cefuroxime continuous infusion targeting 64mg/l serum concentrations.\n\nCefuroxime 4 hourly bolus: Cefuroxime loading dose followed by a continuous infusion dosed according to renal function. Dosed to target a serum concentration of 64mg/L.', 'otherNumAtRisk': 42, 'deathsNumAtRisk': 42, 'otherNumAffected': 0, 'seriousNumAtRisk': 42, 'deathsNumAffected': 0, 'seriousNumAffected': 5}], 'otherEvents': [{'term': 'Clostridium difficile infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 43, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 42, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'Anastomotic leak', 'stats': [{'groupId': 'EG000', 'numAtRisk': 43, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 42, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Unplanned surgical procedure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 43, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 42, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Gastrointestinal bleed', 'stats': [{'groupId': 'EG000', 'numAtRisk': 43, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 42, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Pleural effusion with pleural drain insertion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 43, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 42, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Patients With a Surgical Site Infection', 'denoms': [{'units': 'Participants', 'counts': [{'value': '43', 'groupId': 'OG000'}, {'value': '42', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Standard Regimen', 'description': 'Cefuroxime 1.5grams pre-operatively Repeated every 4 hours\n\nCefuroxime bolus-continuous infusion: Cefuroxime 1.5 grams pre-operatively, repeated 4 hourly during surgery.'}, {'id': 'OG001', 'title': 'Interventional Regimen', 'description': 'Cefuroxime continuous infusion targeting 64mg/l serum concentrations.\n\nCefuroxime 4 hourly bolus: Cefuroxime loading dose followed by a continuous infusion dosed according to renal function. Dosed to target a serum concentration of 64mg/L.'}], 'classes': [{'categories': [{'measurements': [{'value': '10', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Number of patients with a surgical site infection within 30 days of a colorectal surgical procedure.', 'description': "Superficial and deep surgical site infections as defined by the CDC (Centre's for Disease Control) definitions of surgical site infections.", 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Standard Regimen', 'description': 'Cefuroxime 1.5grams pre-operatively Repeated every 4 hours\n\nCefuroxime bolus-continuous infusion: Cefuroxime 1.5 grams pre-operatively, repeated 4 hourly during surgery.'}, {'id': 'FG001', 'title': 'Interventional Regimen', 'description': 'Cefuroxime continuous infusion targeting 64mg/l serum concentrations.\n\nCefuroxime 4 hourly bolus: Cefuroxime loading dose followed by a continuous infusion dosed according to renal function. Dosed to target a serum concentration of 64mg/L.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '45'}, {'groupId': 'FG001', 'numSubjects': '45'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '43'}, {'groupId': 'FG001', 'numSubjects': '42'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '3'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '45', 'groupId': 'BG000'}, {'value': '45', 'groupId': 'BG001'}, {'value': '90', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Standard Dosing', 'description': 'Intravenous (IV) cefuroxime 1.5g bolus administered four-hourly throughout surgery'}, {'id': 'BG001', 'title': 'Intervention Dosing', 'description': 'Cefuroxime bolus-continuous dosing was based on targeting non-protein bound (free) serum concentrations of antibiotic at 64mg/L throughout surgery'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '45', 'groupId': 'BG000'}, {'value': '45', 'groupId': 'BG001'}, {'value': '90', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '58', 'spread': '17', 'groupId': 'BG000'}, {'value': '61', 'spread': '17', 'groupId': 'BG001'}, {'value': '60', 'spread': '17', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'Collection by review of medical records', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '45', 'groupId': 'BG000'}, {'value': '45', 'groupId': 'BG001'}, {'value': '90', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '24', 'groupId': 'BG000'}, {'value': '27', 'groupId': 'BG001'}, {'value': '51', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '21', 'groupId': 'BG000'}, {'value': '18', 'groupId': 'BG001'}, {'value': '39', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'Collection by review of medical records', 'unitOfMeasure': 'Participants'}, {'title': 'Race and Ethnicity Not Collected', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Race and Ethnicity were not collected from any participant.'}], 'populationDescription': 'The analysis population was on an intention to treat basis'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2016-10-10', 'size': 2091916, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2019-05-29T06:29', 'hasProtocol': True}, {'date': '2015-11-24', 'size': 147222, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_001.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2019-08-05T06:43', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['PARTICIPANT']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 90}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-08', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-10', 'completionDateStruct': {'date': '2017-05', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-10-08', 'studyFirstSubmitDate': '2015-05-13', 'resultsFirstSubmitDate': '2019-06-03', 'studyFirstSubmitQcDate': '2015-05-14', 'lastUpdatePostDateStruct': {'date': '2019-10-10', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2019-08-07', 'studyFirstPostDateStruct': {'date': '2015-05-15', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2019-09-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2017-05', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Patients With a Surgical Site Infection', 'timeFrame': 'Number of patients with a surgical site infection within 30 days of a colorectal surgical procedure.', 'description': "Superficial and deep surgical site infections as defined by the CDC (Centre's for Disease Control) definitions of surgical site infections."}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Antibiotic', 'prophylaxis', 'surgical site infection'], 'conditions': ['Surgical Site Infection']}, 'referencesModule': {'references': [{'pmid': '30519893', 'type': 'DERIVED', 'citation': 'Kirby A, Asin-Prieto E, Burns FA, Ewin D, Fatania K, Kailavasan M, Nisar S, Pericleous A, Troconiz IF, Burke D. Colo-Pro: a pilot randomised controlled trial to compare standard bolus-dosed cefuroxime prophylaxis to bolus-continuous infusion-dosed cefuroxime prophylaxis for the prevention of infections after colorectal surgery. Eur J Clin Microbiol Infect Dis. 2019 Feb;38(2):357-363. doi: 10.1007/s10096-018-3435-z. Epub 2018 Dec 5.'}]}, 'descriptionModule': {'briefSummary': "We propose to randomise patients due to undergo colorectal surgery to standard antibiotic prophylaxis or an interventional antibiotic prophylaxis regimen and assess surgical wound infection rates. Standard antibiotic prophylaxis is a pre-operative injection of cefuroxime, repeated every 4 hours. The intervention regimen is a loading dose of cefuroxime followed by a continuous infusion of cefuroxime until the end of surgery. The intervention regimen dosing will be calculated using a patient's renal function and body weight. The intervention regimen will target a free serum drug concentration of 64mg/L. This serum level is 4x the MIC90 for colonising Enterobacteriaceae. The rational for this dosing regimen is summarised below. The primary objective of the study is to reduce by 50% the rate of surgical wound infections after colorectal surgery.", 'detailedDescription': 'An expert assessment is that fT\\>MIC is the measure most likely to be applicable to prophylaxis. But this measure is not achieved by standard prophylaxis regimens. Neither do clinical data suggest this target achieves optimal prophylaxis. Therefore there is an opportunity to optimise antibiotic prophylaxis dosing. As the exposure response-relationship (pharmacodynamic target) is unknown we could either complete a number of studies exploring different relationships, or compare standard treatment to a single regimen which included a number of exposure-response relationships. The two most common exposure-response relationships are the CMAX/MIC ratio and the fT\\>MIC. And it has been reported that killing, as opposed to inhibition used in MIC values, is optimised by achieving 4 times an MIC value. An antibiotic prophylaxis regimen which achieved drug concentrations of 4xMIC for the duration of surgery would therefore achieves a high CMAX/MIC ratio, high T\\>MIC, and optimise bacterial killing. Therefore, standard dose antibiotic prophylaxis will be compared against a PD target dosed antibiotic prophylaxis regimen. The PD target will be a free serum antibiotic concentration of 4xMIC90 for Enterobacteriaceae against cefuroxime. Continuous infusion of antibiotic prophylaxis will ensure there is continuous targeting of this drug level throughout the operation.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion criteria\n\n* Undergoing colorectal surgery (incision, excision or anastomosis of the large bowel, including anastomosis of small to large bowel)\n* Age \\>18.\n* Expected duration of surgery \\> 2hours\n* Creatinine clearance \\> 40 ml/min\n* Cefuroxime/metronidazole are appropriate antibiotic prophylaxis regimens.\n* Patient capable of giving informed consent\n* Patients undergoing colorectal surgery plus additional surgery e.g. plastic surgery, urological surgery, gynaecological surgery.\n* If it is not possible to obtain intra-operative blood samples e.g. difficult vascular access, or pre-operative swabs e.g. anatomy makes it difficult to obtain, patients will be included and this information treated as missing data. Patients on antibiotic treatment for an existing infection (except SSIs) can be included in the study\n\nExclusion Criteria:\n\n* Unable to consent\n* Pregnancy\n* Expected duration of surgery \\<2hours\n* Creatinine clearance \\<40ml/min\n* Individual level microbiological advice for non cefuroxime based prophylaxis\n* Cephalosporin allergy\n* Penicillin allergy (hypersensitivity reaction only)\n* Coumarin (warfarin and acenocoumarol) treatment\n* Active blood borne virus infection e.g. HIV, hepatitis.\n* Seizure history\n* Concurrent use of probenecid\n* Current participation in a research project aimed at reducing SSIs\n* Antibiotics for treatment of a systemic Gram negative infection within 2 hours of initiation of surgery (Vancomycin, Teicoplanin, Daptomycin, Linezolid, Flucloxacillin. Nitrofurantoin and Clarithromycin would be permissible antibiotics without systemic Gram negative antibiotics).\n* A current diagnosis of a SSI at the time of study entry.'}, 'identificationModule': {'nctId': 'NCT02445859', 'acronym': 'Colo-Pro', 'briefTitle': 'Continuous Antibiotic Prophylaxis in Colorectal Surgery', 'organization': {'class': 'OTHER', 'fullName': 'University of Leeds'}, 'officialTitle': 'Colo-Pro Pilot: A Pilot Study to Compare Standard Single Dose Antibiotic Prophylaxis to Bolus-continuous Infusion Dosed Antibiotic Prophylaxis for the Prevention of Infections After Colorectal Surgery', 'orgStudyIdInfo': {'id': 'MB15/130'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Standard regimen', 'description': 'Cefuroxime 1.5grams pre-operatively Repeated every 4 hours', 'interventionNames': ['Drug: Cefuroxime 4 hourly bolus']}, {'type': 'EXPERIMENTAL', 'label': 'Interventional regimen', 'description': 'Cefuroxime continuous infusion targeting 64mg/l serum concentrations.', 'interventionNames': ['Drug: Cefuroxime 4 hourly bolus']}], 'interventions': [{'name': 'Cefuroxime 4 hourly bolus', 'type': 'DRUG', 'description': 'Cefuroxime loading dose followed by a continuous infusion dosed according to renal function. Dosed to target a serum concentration of 64mg/L.', 'armGroupLabels': ['Interventional regimen', 'Standard regimen']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'LS1 3EX', 'city': 'Leeds', 'state': 'West Yorkshire', 'country': 'United Kingdom', 'facility': 'Leeds Teaching Hospitals NHS Trust', 'geoPoint': {'lat': 53.79648, 'lon': -1.54785}}], 'overallOfficials': [{'name': 'Andrew Kirby', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'The University of Leeds'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Leeds', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate clinical professor', 'investigatorFullName': 'Andrew Kirby', 'investigatorAffiliation': 'University of Leeds'}}}}