Ignite Creation Date:
2025-12-24 @ 6:44 PM
Ignite Modification Date:
2026-02-28 @ 7:11 PM
Study NCT ID:
NCT05618457
Status:
RECRUITING
Last Update Posted:
2024-03-01
First Post:
2022-10-30
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Adjustment of Aminoglycoside Dosing Based on Peak Serum Concentration and Bacterial Minimal Inhibitory Concentration
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 151}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2021-12-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-02', 'completionDateStruct': {'date': '2025-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-02-28', 'studyFirstSubmitDate': '2022-10-30', 'studyFirstSubmitQcDate': '2022-11-08', 'lastUpdatePostDateStruct': {'date': '2024-03-01', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-11-16', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Efficacy outcome', 'timeFrame': 'up to 1 week after end of therapy', 'description': 'proportion of patients where treatment failure was suspected and attributed to AG dose reduction'}, {'measure': 'Renal outcome', 'timeFrame': 'up to 1 week after end of therapy', 'description': 'Proportion of patients fulfilling RIFLE criteria (any category) baseline'}, {'measure': 'Renal outcome', 'timeFrame': 'up to 1 week after end of therapy', 'description': 'Mean serum creatinine change at end of therapy vs. baseline'}, {'measure': 'Aminoglycoside dosing outcomes:', 'timeFrame': 'up to 1 week after end of therapy', 'description': 'Proportion of patients where AG dose was adjusted based on PK-PD parameters'}, {'measure': 'Aminoglycoside dosing outcomes:', 'timeFrame': 'up to 1 week after end of therapy', 'description': 'Mean change in AG dose following adjustment'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Aminoglycosides', 'Minimal Inhibitory Concentration (MIC)', 'Gram negative', 'PK/PD', 'Peak concentration (Cmax)'], 'conditions': ['Aminoglycoside Dosing Based on PK/PD Characteristics']}, 'descriptionModule': {'briefSummary': "Aminoglycoside (AG) antibiotics have been in clinical use since the 1960s for treating various infections. The main safety concern related to AG use is nephrotoxicity. Based on validated pharmacokinetic-pharmacodynamic (PK-PD) principles shown to predict efficacy, AG dosing has shifted over the past 2 decades from multiple daily dosing to extended-interval dosing, with concomitant reduction in nephrotoxicity. Currently, AG daily dose is calculated according to the patients' adjusted body weight, assuming a common minimal inhibitory concentration (MIC) value.\n\nWe hypothesize that once pathogen identity and actual MIC become available, AG daily doses may be further adjusted, using the same PK-PD indices.\n\nIn order to investigate this hypothesis, we are conducting a prospective clinical study in which AG doses will be adjusted based on patient- and pathogen-specific factors, while assessing efficacy and safety.", 'detailedDescription': 'Intervention for all eligible patients:\n\ncalculation of Cmax/MIC based on MIC determination and timely peak level determination performed 30 minutes after the first or second AG dose following pathogen identity and MIC availability (as Individual timely monitoring is essential for individual dose adjustment, this will require one additional blood sample to routine clinical practice). If a peak-level monitoring is not available, Cmax will be assessed using commonly used pharmacokinetic prediction tools (equations/calculators.\n\n1. If Cmax/MIC=8-12 - no intervention (aminoglycoside dose unchanged).\n2. If Cmax/MIC\\>12 - decreasing AG dose accordingly, based on clinical calculators, to achieve target Cmax/MIC\\~10;\n3. If Cmax/MIC\\<8 - increasing AG dose accordingly, based on clinical calculators, to achieve target Cmax/MIC\\~10; If the calculated dose is larger than acceptable AG dosing, an infectious diseases physician will be consulted for need for alternative therapy.\n4. If AG dose has been adjusted, ascertaining PK/PD target attainment (repeat timely peak level determination following dose adjustment).\n5. Monitoring clinical and microbiological course and outcomes:\n\n5.1 Clinical efficacy microbiological and clinical cure, in-hospital mortality 5.2 Safety - renal function during therapy, at end of therapy and at discharge or at day 7 after end of therapy, whichever is earlier. Any deterioration in renal function compared with baseline will be categorized according to the RIFLE criteria.\n\n5.3 Aminoglycoside dosing data (proportion end extent of dose adjustments performed)'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': '1. Adult patients (≥18yr)\n2. Any infection treated with IV gentamycin or amikacin and approved by the consultant infectious diseases specialist, excluding neurosurgical infections, pneumonia, endocarditis or endovascular infections\n3. Normal renal function or mild renal impairment (eGFR≥40ml/min)\n4. On extended-interval AG and an expected remaining AG course of at least 4 days\n5. At least one microbiological specimen with identification of an AG-susceptible pathogen and MIC determination and\n6. Signed informed consent form\n\nExclusion Criteria:\n\n1. Age\\<18yr\n2. Neurosurgical infections, pneumonia, endocarditis or endovascular infections\n3. eGFR\\<40ml/min\n4. Empirical aminoglycoside treatment\n5. Non Gram-negative pathogen\n6. No MIC available for the pathogen\n7. Expected remaining treatment duration of less than 4 days'}, 'identificationModule': {'nctId': 'NCT05618457', 'briefTitle': 'Adjustment of Aminoglycoside Dosing Based on Peak Serum Concentration and Bacterial Minimal Inhibitory Concentration', 'organization': {'class': 'OTHER', 'fullName': 'Hadassah Medical Organization'}, 'officialTitle': 'Adjustment of Aminoglycoside Dosing Based on Peak Serum Concentration and Bacterial Minimal Inhibitory Concentration', 'orgStudyIdInfo': {'id': '0557-21-HMO'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'OTHER', 'label': 'Aminoglycoside dose adjustment', 'description': 'Eligible patients will be assessed for attainment of PK/PD target under standard dosing, dose adjustment to attain target will be proposed where appropriate', 'interventionNames': ['Drug: Aminoglycoside dose adjustment']}], 'interventions': [{'name': 'Aminoglycoside dose adjustment', 'type': 'DRUG', 'description': 'Eligible patients may have the aminoglycoside dose adjusted based on pathogen MIC, to attain the PK/PD target of Cam/MIC\\~10 (8-12)', 'armGroupLabels': ['Aminoglycoside dose adjustment']}]}, 'contactsLocationsModule': {'locations': [{'zip': '12000', 'city': 'Jerusalem', 'status': 'RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Maya Korem, MD', 'role': 'CONTACT', 'email': 'MayaK@hadassah.org.il', 'phone': '+972508573173'}, {'name': 'EHud Horwitz, PhD', 'role': 'CONTACT', 'email': 'ehud.horwitz@mail.huji.ac.il', 'phone': '+972502799755'}, {'name': 'Jacob Strahilevitz, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Jonathan Oster, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Sara Israel, MD', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Hadassah Hebrew University Medical Center', 'geoPoint': {'lat': 31.76904, 'lon': 35.21633}}], 'centralContacts': [{'name': 'Ehud Horwitz, PhD', 'role': 'CONTACT', 'email': 'ehud.horwitz@mail.huji.ac.il', 'phone': '+972502799755'}, {'name': 'Maya Korem, MD', 'role': 'CONTACT', 'email': 'MayaK@hadassah.org.il', 'phone': '+972508573173'}], 'overallOfficials': [{'name': 'Maya Korem, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Director, Antimicrobial Stewardship Program'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED', 'description': 'YES'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Hadassah Medical Organization', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}