Ignite Creation Date:
2025-12-25 @ 2:18 AM
Ignite Modification Date:
2026-02-03 @ 1:40 AM
Study NCT ID:
NCT03090334
Status:
TERMINATED
Last Update Posted:
2024-08-28
First Post:
2017-03-18
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A B-D-Glucan Driven Antifungal Stewardship Approach for Invasive Candidiasis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D058365', 'term': 'Candidiasis, Invasive'}, {'id': 'D059413', 'term': 'Intraabdominal Infections'}], 'ancestors': [{'id': 'D002177', 'term': 'Candidiasis'}, {'id': 'D009181', 'term': 'Mycoses'}, {'id': 'D001423', 'term': 'Bacterial Infections and Mycoses'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D000072742', 'term': 'Invasive Fungal Infections'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['CARE_PROVIDER'], 'maskingDescription': 'Care provider will be blinded to result of BG in patients enrolled in the standard of care arm'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 34}}, 'statusModule': {'whyStopped': 'Insufficient rate of accrual due to the start of a concomitant similar study', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2017-03-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-08', 'completionDateStruct': {'date': '2019-06-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-08-26', 'studyFirstSubmitDate': '2017-03-18', 'studyFirstSubmitQcDate': '2017-03-18', 'lastUpdatePostDateStruct': {'date': '2024-08-28', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-03-24', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-06-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Antifungal consumption', 'timeFrame': '28 days', 'description': 'Days of antifungal consumption will be compared between the two groups'}, {'measure': 'Mortality', 'timeFrame': '28 days', 'description': '28-day mortality will be compared between the two groups'}, {'measure': 'Length of stay', 'timeFrame': '28 days', 'description': 'Length of stay in ICU will be compared between the two groups'}], 'secondaryOutcomes': [{'measure': 'Accuracy of BG', 'timeFrame': '28 days', 'description': 'sensitivity, specificity, positive predictive value, negative predictive value of BG in the diagnosis of invasive candidiasis'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['beta-d-glucan', 'abdominal candidiasis'], 'conditions': ['Invasive Candidiases', 'Abdominal Infection']}, 'referencesModule': {'references': [{'pmid': '24105327', 'type': 'BACKGROUND', 'citation': 'Bassetti M, Marchetti M, Chakrabarti A, Colizza S, Garnacho-Montero J, Kett DH, Munoz P, Cristini F, Andoniadou A, Viale P, Rocca GD, Roilides E, Sganga G, Walsh TJ, Tascini C, Tumbarello M, Menichetti F, Righi E, Eckmann C, Viscoli C, Shorr AF, Leroy O, Petrikos G, De Rosa FG. A research agenda on the management of intra-abdominal candidiasis: results from a consensus of multinational experts. Intensive Care Med. 2013 Dec;39(12):2092-106. doi: 10.1007/s00134-013-3109-3. Epub 2013 Oct 9.'}, {'pmid': '22423135', 'type': 'BACKGROUND', 'citation': 'Kollef M, Micek S, Hampton N, Doherty JA, Kumar A. Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis. 2012 Jun;54(12):1739-46. doi: 10.1093/cid/cis305. Epub 2012 Mar 15.'}, {'pmid': '25091787', 'type': 'BACKGROUND', 'citation': 'Maubon D, Garnaud C, Calandra T, Sanglard D, Cornet M. Resistance of Candida spp. to antifungal drugs in the ICU: where are we now? Intensive Care Med. 2014 Sep;40(9):1241-55. doi: 10.1007/s00134-014-3404-7. Epub 2014 Aug 5.'}, {'pmid': '23315320', 'type': 'BACKGROUND', 'citation': 'Clancy CJ, Nguyen MH. Finding the "missing 50%" of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013 May;56(9):1284-92. doi: 10.1093/cid/cit006. Epub 2013 Jan 11.'}]}, 'descriptionModule': {'briefSummary': "This is a multicenter, prospective, open-label, randomized trial. Patients with severe abdominal condition developing severe sepsis or septic shock and receiving broad spectrum antibiotic and antifungal treatment will be randomized (1:1) to:\n\n1. discontinue antifungal treatment based on negative (\\<80 pg/ml) result of 1,3 beta-d-glucan performed on day 0,3,6 and 10\n2. continue antifungal treatment according with attending physician's decision.", 'detailedDescription': "Primary objective:\n\nOur objective is to establish whether a strategy based on beta-d-glucan (BG) assessment could achieve reduced antifungal consumption in patients with severe abdominal condition developing severe sepsis and septic shock without any impact on the outcome Secondary objectives i) Assess the accuracy of BG in the diagnosis of invasive candidiasis (IC) in in critically ill patients with a severe abdominal condition who develop severe sepsis or septic shock.\n\nii) Describe the changes over the time of BG value according with colonization status, infection or none the aforementioned events.\n\nMaterial and Methods Study design: a multicenter, open label, randomized trial Population: all the patients with a severe abdominal condition who develop a severe sepsis or septic shock.\n\n1. Inclusion Criteria:\n\n 1. adult (≥ 18 year) patients;\n 2. signed informed consent before surgical procedure;\n 3. severe sepsis or septic shock;\n 4. at least one of the following conditions: i) post-operative peritonitis, ii) recurrent gastrointestinal perforation, iii) post-operative hepatobiliary and/or pancreatic disorders including necrotizing pancreatitis, iv) post-operative intra-abdominal abscess, and v) anastomotic leak.\n2. Exclusion criteria a. diagnosis of candidiasis before the enrollment b. exposure in the past 30 days to any antifungal treatment or diagnosis of invasive fungal infection; c. pregnancy or lactation; d. history of allergy to any of the antifungal drugs; e. major immunosuppression conditions including: i. neutropenia (\\<0.5 × 109 neutrophils/L \\[\\<500 neutrophils/mm3\\] for \\>10 days), ii. receipt of an allogeneic stem cell transplant or solid organ transplantation, iii. inherited severe immunodeficiency (such as chronic granulomatous disease or severe combined immunodeficiency), iv. HIV infection with lymphocyte T CD4+ cell count \\< 200/mmc. f. patients with poor prognosis or unable to sign informed consent.\n\nProcedures Pre-randomization procedures\n\nAt the time of patient enrollment (within 24 h from onset of severe sepsis/septic shock), a standardized diagnostic work-up must be performed including at least:\n\ni) two sets of blood cultures; ii) 5 surveillance cultures (rectal swab, urine culture, pharyngeal swab, axillary swab, groin swab).\n\niii) in case of re-intervention or percutaneous drainage: Gram stain and culture of intra-abdominal samples; iv) serum BG determination. Antibiotic and antifungal empirical therapy should be started immediately after collection of microbiological samples according with a predefined standard of care (see appendix 1). Once completed this procedures patients will proceed to randomization.\n\nRandomization Patient eligible for the study after the beginning of antifungal therapy will be randomized 1:1 to receive (Group A) a BG driven de-escalation strategy or (Group B) a course of antifungal treatment based on the care provider's decision.\n\nIn both groups, if cultures yield invasive candidiasis (see below) the patient will be managed in according with guidelines and excluded from the per-protocol analysis.\n\nIn both groups, BG determination will be repeated at day +3, +6 and +10 after starting antifungal therapy.\n\nRandomization will be carried out providing closed envelopes to the participating centers immediately before the study onset."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* a. adult (≥ 18 year) patients; b. signed informed consent before surgical procedure; c. severe sepsis or septic shock; d. at least one of the following conditions: i) post-operative peritonitis, ii) recurrent gastrointestinal perforation, iii) post-operative hepatobiliary and/or pancreatic disorders including necrotizing pancreatitis, iv) post-operative intra-abdominal abscess, and v) anastomotic leak.\n\nExclusion Criteria:\n\n* a. diagnosis of candidiasis before the enrollment b. exposure in the past 30 days to any antifungal treatment or diagnosis of invasive fungal infection; c. pregnancy or lactation; d. history of allergy to any of the antifungal drugs; e. major immunosuppression conditions including: i. neutropenia (\\<0.5 × 109 neutrophils/L \\[\\<500 neutrophils/mm3\\] for \\>10 days), ii. receipt of an allogeneic stem cell transplant or solid organ transplantation, iii. inherited severe immunodeficiency (such as chronic granulomatous disease or severe combined immunodeficiency), iv. HIV infection with lymphocyte T CD4+ cell count \\< 200/mmc. f. patients with poor prognosis or unable to sign informed consent.'}, 'identificationModule': {'nctId': 'NCT03090334', 'briefTitle': 'A B-D-Glucan Driven Antifungal Stewardship Approach for Invasive Candidiasis', 'organization': {'class': 'OTHER', 'fullName': 'University of Bologna'}, 'officialTitle': 'A B-D-Glucan Driven Antifungal Stewardship Approach to Manage Empirical Therapy in Patients at Very High Risk for Invasive Candidiasis: a Randomized Controlled Trial', 'orgStudyIdInfo': {'id': 'BDG-ETHIC'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'De-escalation', 'description': 'In this group, investigators will manage the antifungal therapy according to the BG levels as follows:\n\n1. antifungal therapy will be stopped immediately after the BG response in case of serum BG \\<80 pg/ml in presence of clinical stability (CS);\n2. antifungal therapy will be continued until further BG determination, both for BG levels between 80-200 pg/ml and for BG \\<80 pg/ml in patients without CS. In these cases, if the following BG value is \\<80 pg/ml antifungal therapy will be stopped independently from the CS achievement.\n3. antifungal therapy will be continued until day 10 for BG levels \\>200 pg/ml', 'interventionNames': ['Diagnostic Test: De-escalation']}, {'type': 'NO_INTERVENTION', 'label': 'Standard of care', 'description': "In this group antifungal treatment will be continued until clinician's decision.\n\nInvestigators will be blinded to the BG levels of patients enrolled in this arm, The BG results will be faxed directly to the coordinating center."}], 'interventions': [{'name': 'De-escalation', 'type': 'DIAGNOSTIC_TEST', 'description': 'Antifungal therapy will be stopped according with BG results', 'armGroupLabels': ['De-escalation']}]}, 'contactsLocationsModule': {'locations': [{'zip': '40138', 'city': 'Bologna', 'country': 'Italy', 'facility': 'Azienda Ospealiero Universitaria di Bologna Policlinico S.Orsola-Malpighi', 'geoPoint': {'lat': 44.49381, 'lon': 11.33875}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Bologna', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD', 'investigatorFullName': 'Maddalena Giannella', 'investigatorAffiliation': 'University of Bologna'}}}}