Ignite Creation Date:
2025-12-24 @ 5:05 PM
Ignite Modification Date:
2025-12-24 @ 5:05 PM
Study NCT ID:
NCT03796650
Status:
TERMINATED
Last Update Posted:
2024-09-19
First Post:
2019-01-04
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Fecal Transplantation for Primary Clostridium Difficile Infection
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003015', 'term': 'Clostridium Infections'}, {'id': 'D003967', 'term': 'Diarrhea'}], 'ancestors': [{'id': 'D016908', 'term': 'Gram-Positive Bacterial Infections'}, {'id': 'D001424', 'term': 'Bacterial Infections'}, {'id': 'D001423', 'term': 'Bacterial Infections and Mycoses'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D012817', 'term': 'Signs and Symptoms, Digestive'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000069467', 'term': 'Fecal Microbiota Transplantation'}, {'id': 'D014640', 'term': 'Vancomycin'}], 'ancestors': [{'id': 'D001691', 'term': 'Biological Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D006020', 'term': 'Glycopeptides'}, {'id': 'D006001', 'term': 'Glycoconjugates'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR'], 'maskingDescription': 'An open-label, partly assessor blinded trial.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Randomized clinical trial with two parallel treatment arms with a 1:1 allocation.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 104}}, 'statusModule': {'whyStopped': 'Pre-specified non-inferiority criterion met at interim analysis.', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2019-07-17', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-09', 'completionDateStruct': {'date': '2024-04-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-09-09', 'studyFirstSubmitDate': '2019-01-04', 'studyFirstSubmitQcDate': '2019-01-07', 'lastUpdatePostDateStruct': {'date': '2024-09-19', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-01-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-04-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Fecal composition and treatment outcome', 'timeFrame': '60 days', 'description': 'Correlation in fecal composition changes before versus after treatment, and treatment outcome (such as bacterial diversity and fecal short chain fatty acids).\n\nSubgroup analyses will be performed for sex, age, co-morbidities, and FMT donor.'}], 'primaryOutcomes': [{'measure': 'Patients with durable cure', 'timeFrame': '60 days', 'description': 'Proportion of patients with primary clinical cure at day 14 after treatment start and no recurrent C. difficile infection during 60 days after treatment start, with the assigned treatment alone.'}], 'secondaryOutcomes': [{'measure': 'Patients with durable cure with additional treatment.', 'timeFrame': '60 days', 'description': 'Proportion of patients with primary clinical cure at day 14 after treatment start and no recurrent C. difficile infection during 60 days after treatment start, with or without the need of additional treatment (FMT, metronidazole or vancomycin).'}, {'measure': 'Treatment adverse events', 'timeFrame': '60 and 365 days', 'description': 'Proportion of patients with adverse events.'}, {'measure': 'Patients with long-time cure', 'timeFrame': '365 days', 'description': 'Proportion of patients with primary clinical cure at day 14 after treatment start and no recurrent C. difficile infection during 60 days after treatment start, and without recurrent C. difficile infection within 365 days after treatment start.'}, {'measure': 'Health-economic evaluation', 'timeFrame': '365 days', 'description': 'Health-economic analysis of the two compared treatment modalities'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Clostridium difficile', 'Intestinal microbiota therapy', 'Fecal microbiota transplantation', 'Investigator-initiated', 'Antibiotics', 'Diarrhea'], 'conditions': ['Clostridium Difficile Infection']}, 'referencesModule': {'references': [{'pmid': '29562266', 'type': 'BACKGROUND', 'citation': 'McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994. doi: 10.1093/cid/ciy149.'}, {'pmid': '29860912', 'type': 'BACKGROUND', 'citation': 'Juul FE, Garborg K, Bretthauer M, Skudal H, Oines MN, Wiig H, Rose O, Seip B, Lamont JT, Midtvedt T, Valeur J, Kalager M, Holme O, Helsingen L, Loberg M, Adami HO. Fecal Microbiota Transplantation for Primary Clostridium difficile Infection. N Engl J Med. 2018 Jun 28;378(26):2535-2536. doi: 10.1056/NEJMc1803103. Epub 2018 Jun 2. No abstract available.'}, {'pmid': '25875259', 'type': 'BACKGROUND', 'citation': 'Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med. 2015 Apr 16;372(16):1539-48. doi: 10.1056/NEJMra1403772. No abstract available.'}, {'pmid': '23718168', 'type': 'BACKGROUND', 'citation': 'van Nood E, Dijkgraaf MG, Keller JJ. Duodenal infusion of feces for recurrent Clostridium difficile. N Engl J Med. 2013 May 30;368(22):2145. doi: 10.1056/NEJMc1303919. No abstract available.'}, {'pmid': '23511459', 'type': 'BACKGROUND', 'citation': 'Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013 Apr;108(4):500-8. doi: 10.1038/ajg.2013.59. Epub 2013 Mar 19.'}, {'pmid': '40523286', 'type': 'DERIVED', 'citation': 'Juul FE, Bretthauer M, Johnsen PH, Samy F, Tonby K, Berdal JE, Hoff DAL, Ofstad EH, Abraham A, Seip B, Wiig H, Rognstad OB, Glad IF, Valeur J, Nissen-Lie AE, Ness-Jensen E, Lund KMA, Skjevling LK, Hanevik K, Skudal H, Melsom EJ, Boyar R, Cooper TJ, Ranheim TE, Riise EM, Adami HO, Kalager M, Loberg M, Garborg KK. Fecal Microbiota Transplantation Versus Vancomycin for Primary Clostridioides difficile Infection : A Randomized Controlled Trial. Ann Intern Med. 2025 Jul;178(7):940-947. doi: 10.7326/ANNALS-24-03285. Epub 2025 Jun 17.'}], 'seeAlsoLinks': [{'url': 'https://www.med.uio.no/helsam/english/research/groups/clinical-effectiveness/index.html', 'label': "Investigating research group' home page"}]}, 'descriptionModule': {'briefSummary': 'In this randomized controlled trial the investigators want to compare the effect of one-time rectal instillation of fecal microbiota transplantation, compared to a ten-day antibiotic course for the treatment of primary Clostridium difficile infection (CDI). The investigators hypothetsize that the instillation of feces from a healthy donor will be non-inferior to vancomycin in inducing a durable cure.', 'detailedDescription': 'Up to one third of patients with clostridium difficile infection treated with antibiotics experience recurrent or relapsing symptoms within a few weeks. Even with subsequent antibiotic treatment, multiple recurrences/relapses are frequent. Fecal microbiota transplantation (FMT) has been shown to be significantly more effective in curing recurrent CDI than repeated antibiotic treatment. In current guidelines, FMT is proposed as a treatment option after multiple recurrences/relapses of CDI. The rationale to reserve transplantation of donor feces for recurrent and difficult cases of CDI is a possible risk of pathogen transmittance and the process of finding a donor and screen for communicable disease.\n\nThe effect of FMT for recurrent CDI, however, suggests that this therapy may be more effective than antibiotics in inducing a durable cure also for primary CDI. If the therapeutic effect of FMT proves to be equal (non-inferior) or more effective than antibiotics, FMT may be the preferable treatment option due to favourable ecological impact compared to antibiotics. In an era with increasing concerns about overuse of antibiotics and emergence of antibiotic resistant bacteria, it is important to investigate therapeutic alternatives that may reduce the need for antibiotics.\n\nThis trial is a phase III multicentre, randomized controlled, open-label non-inferiority parallel group trial with two arms (FMT and antibiotics), and is a continuation of the phase II trial IMT for Primary Clostridium Difficile Infection (NCT02301000). In the current trial, patients with Clostridium difficile infection and no previous CDI within 12 months prior to inclusion will be randomized 1:1 to FMT or 10 days of guideline-recommended antibiotic therapy (vancomycin 125 mg four times a day).\n\nPatients are recruited in Norwegian hospitals.\n\nThe investigators plan to use frozen microbiota, because supply is easier to organize, compared to fresh fecal samples. Patients in the FMT treatment group will receive one rectal dose of FMT, originating from screened, healthy donors. Patients who are not cured by the first dose is offered a protocol defined additional FMT treatment. In the case of clinical deterioration, appropriate measures will be undertaken according to current guidelines.\n\nPatient treatment outcomes are evaluated after 14, 60 and 365 days from inclusion and treatment initiation.\n\nAn interim analysis is planned after inclusion of the first 94 patients (corresponding to 50% of the planned number of patients).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients, ≥18 years with primary C. difficile infection, defined by the following three criteria:\n\n 1. Diarrhea as defined by the WHO (≥3 loose stools per day), and\n 2. Positive stool test for toxin producing C. difficile, and\n 3. No evidence of previous C. difficile infection during 365 days before enrolment.\n* Written informed consent\n\nExclusion Criteria:\n\n* Known presence of other stool pathogens known to cause diarrhea.\n* Ongoing antibiotic treatment for other infections that cannot be stopped before study treatment administration.\n* Inflammatory bowel disease or microscopic colitis.\n* \\< 3 months life expectancy.\n* Serious immunodeficiency, defined as one of the following:\n\n * Ongoing or recent chemotherapy and current or expected neutropenia with neutrophil count of \\< 500/μL.\n * Active severe immunocompromising disease.\n* Inability to comply with protocol requirements.\n* Need of intensive care.\n* Known irritable bowel syndrome, diarrheal type.\n* Pregnancy or nursing.\n* Known or suspected toxic megacolon or ileus.\n* Total or subtotal colectomy, ileostomy or colonostomy.\n* Contraindications for rectal catheter insertion\n* Known hypersensitivity or other contraindications to vancomycin'}, 'identificationModule': {'nctId': 'NCT03796650', 'acronym': 'COLONIZE', 'briefTitle': 'Fecal Transplantation for Primary Clostridium Difficile Infection', 'organization': {'class': 'OTHER', 'fullName': 'Oslo University Hospital'}, 'officialTitle': 'COmparative Effectiveness of IntestinaL MicrobiOta Versus VaNcomycin for Primary C. Difficile Infection - RandomiZEd Trials', 'orgStudyIdInfo': {'id': 'COLONIZE'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Fecal microbiota transplantation', 'description': 'Fecal microbiota from healthy, screened stool donors at the University Hospital of North Norway. Patients will receive one FMT enema immediately after enrolment.', 'interventionNames': ['Other: Fecal microbiota transplantation']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Antibiotic treatment', 'description': 'Patients randomized to the control group will receive a ten-day course of oral vancomycin four times a day. This is according to international guidelines for primary C. difficile treatment.', 'interventionNames': ['Drug: Vancomycin']}], 'interventions': [{'name': 'Fecal microbiota transplantation', 'type': 'OTHER', 'otherNames': ['FMT', 'IMT', 'Bacteriotherapy'], 'description': '50 g donor feces suspended in saline with added glycerol, administered by a enema kit.', 'armGroupLabels': ['Fecal microbiota transplantation']}, {'name': 'Vancomycin', 'type': 'DRUG', 'description': 'Peroral vancomycin 125 mg q.i.d. for ten days.', 'armGroupLabels': ['Antibiotic treatment']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1346', 'city': 'Sandvika', 'state': 'Gjettum', 'country': 'Norway', 'facility': 'Vestre Viken HF, Bærum Hospital', 'geoPoint': {'lat': 64.46377, 'lon': 13.59125}}, {'zip': '0319', 'city': 'Oslo', 'state': 'Oslo County', 'country': 'Norway', 'facility': 'Diakonhjemmet Hospital', 'geoPoint': {'lat': 59.91273, 'lon': 10.74609}}, {'city': 'Ålesund', 'country': 'Norway', 'facility': 'Ålesund Sjukehus', 'geoPoint': {'lat': 62.47225, 'lon': 6.15492}}, {'city': 'Bergen', 'country': 'Norway', 'facility': 'Haukeland universitetssykehus', 'geoPoint': {'lat': 60.39299, 'lon': 5.32415}}, {'zip': '8092', 'city': 'Bodø', 'country': 'Norway', 'facility': 'Nordlandssykehuset', 'geoPoint': {'lat': 67.28267, 'lon': 14.37513}}, {'city': 'Grålum', 'country': 'Norway', 'facility': 'Sykehuset Østfold Kalnes', 'geoPoint': {'lat': 59.29048, 'lon': 11.06668}}, {'city': 'Harstad', 'country': 'Norway', 'facility': 'UNN Harstad', 'geoPoint': {'lat': 68.79833, 'lon': 16.54165}}, {'city': 'Kristiansand', 'country': 'Norway', 'facility': 'Sørlandet Hospital HF', 'geoPoint': {'lat': 58.14671, 'lon': 7.9956}}, {'city': 'Levanger', 'country': 'Norway', 'facility': 'Sykehuset Levanger', 'geoPoint': {'lat': 63.74644, 'lon': 11.29963}}, {'city': 'Lillehammer', 'country': 'Norway', 'facility': 'Sykehuset Innlandet HF', 'geoPoint': {'lat': 61.11514, 'lon': 10.46628}}, {'zip': '1478', 'city': 'Lørenskog', 'country': 'Norway', 'facility': 'Akershus University Hospital'}, {'city': 'Oslo', 'country': 'Norway', 'facility': 'Lovisenberg sykehus', 'geoPoint': {'lat': 59.91273, 'lon': 10.74609}}, {'city': 'Oslo', 'country': 'Norway', 'facility': 'Oslo University Hospital Rikshospitalet', 'geoPoint': {'lat': 59.91273, 'lon': 10.74609}}, {'city': 'Oslo', 'country': 'Norway', 'facility': 'Oslo University Hospital Ullevål', 'geoPoint': {'lat': 59.91273, 'lon': 10.74609}}, {'city': 'Skien', 'country': 'Norway', 'facility': 'Telemark Hospital HF', 'geoPoint': {'lat': 59.20962, 'lon': 9.60897}}, {'city': 'Stavanger', 'country': 'Norway', 'facility': 'Stavanger University Hospital', 'geoPoint': {'lat': 58.97005, 'lon': 5.73332}}, {'city': 'Tromsø', 'country': 'Norway', 'facility': 'UNN Tromsø', 'geoPoint': {'lat': 69.6489, 'lon': 18.95508}}, {'city': 'Tønsberg', 'country': 'Norway', 'facility': 'Sykehuset i Vestfold', 'geoPoint': {'lat': 59.26754, 'lon': 10.40762}}], 'overallOfficials': [{'name': 'Michael Bretthauer, MD, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Oslo Universitetssykehus HF, Rikshospitalet'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED', 'description': 'The trial adheres to data sharing policies of the ICMJE. Data sharing is considered for each request by the principal investigators. Data sharing is not granted if they overlap with planned analyses. Data sharing requires all approvals by relevant authorities. Costs for data sharing will not be covered by the study group.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Oslo University Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'South-Eastern Norway Regional Health Authority', 'class': 'OTHER'}, {'name': 'University Hospital of North Norway', 'class': 'OTHER'}, {'name': 'Haukeland University Hospital', 'class': 'OTHER'}, {'name': 'Helse Nord-Trøndelag HF', 'class': 'OTHER'}, {'name': 'Vestre Viken Hospital Trust', 'class': 'OTHER'}, {'name': 'The Hospital of Vestfold', 'class': 'OTHER'}, {'name': 'Sykehuset Telemark', 'class': 'OTHER_GOV'}, {'name': 'Alesund Hospital', 'class': 'OTHER'}, {'name': 'University Hospital, Akershus', 'class': 'OTHER'}, {'name': 'Lovisenberg Diakonale Hospital', 'class': 'OTHER'}, {'name': 'Sorlandet Hospital HF', 'class': 'OTHER_GOV'}, {'name': 'Ostfold Hospital Trust', 'class': 'OTHER'}, {'name': 'Diakonhjemmet Hospital', 'class': 'OTHER'}, {'name': 'Nordlandssykehuset HF', 'class': 'OTHER'}, {'name': 'Sykehuset Innlandet HF', 'class': 'OTHER'}, {'name': 'Helse Stavanger HF', 'class': 'OTHER_GOV'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Joint Principal Investigator', 'investigatorFullName': 'Kjetil Garborg', 'investigatorAffiliation': 'Oslo University Hospital'}}}}