Ignite Creation Date:
2025-12-24 @ 11:40 PM
Ignite Modification Date:
2026-01-05 @ 5:32 PM
Study NCT ID:
NCT04493151
Status:
COMPLETED
Last Update Posted:
2024-08-07
First Post:
2020-07-27
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Imipenem/Cilastatin/Relebactam PK in ECMO
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018805', 'term': 'Sepsis'}], 'ancestors': [{'id': 'D007239', 'term': 'Infections'}, {'id': 'D018746', 'term': 'Systemic Inflammatory Response Syndrome'}, {'id': 'D007249', 'term': 'Inflammation'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000633884', 'term': 'imipenem, cilastatin and relebactam'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'Joseph.Kuti@hhchealth.org', 'phone': '(860) 972-3612', 'title': 'Dr. Joseph L. Kuti, PharmD, FIDP, FCCP', 'organization': 'Center for Anti-Infective Research and Development, Hartford Hospital'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'A study limitation is the protocol defined exclusion of patients on concomitant continuous renal replacement therapy (CRRT), which is common in patients receiving ECMO (extracorporeal membrane oxygenation). Dosing modifications may be necessary in patients receiving both CRRT and ECMO.'}}, 'adverseEventsModule': {'timeFrame': 'Adverse events were collected over a 48 hour window, from the first imipenem-relebactam dose (0 hour) to the end of blood sampling (6 hours), plus an 24 hour observation window after the last sample was collected, culminating with physical exam. Note: 8 subjects were enrolled and received imipenem-relebactam. Although only 7 subjects were included in results analysis due to inability to obtain blood samples in 1 subject, all 8 subjects are included in the adverse event reporting.', 'description': 'Adverse event - any pathologic or unintended change in the structure (signs), function (symptoms), or chemistry (laboratory values) of the body associated with the use of the study drug, whether or not considered drug related: MILD - present, but easily tolerated MODERATE - discomfort that interferes with usual activities SEVERE - incapacitating, inability to work or do usual activities', 'eventGroups': [{'id': 'EG000', 'title': 'Imipenem-Cilastatin-Relebactam', 'description': 'Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.\n\nImipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.', 'otherNumAtRisk': 8, 'deathsNumAtRisk': 8, 'otherNumAffected': 3, 'seriousNumAtRisk': 8, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Alkaline Phosphate Increase', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'C. difficile Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Increasing Leukocytosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Aspartate Aminotransferase Increase', 'stats': [{'groupId': 'EG000', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Imipenem Clearance', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Imipenem-Cilastatin-Relebactam', 'description': 'Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.\n\nImipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.'}], 'classes': [{'categories': [{'measurements': [{'value': '15.21', 'spread': '6.52', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).', 'description': 'The clearance in liters/hour of imipenem from the plasma of critically ill patients receiving ECMO.', 'unitOfMeasure': 'Liters per hour', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Relebactam Clearance', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Imipenem-Cilastatin-Relebactam', 'description': 'Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.\n\nImipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.'}], 'classes': [{'categories': [{'measurements': [{'value': '6.95', 'spread': '1.34', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).', 'description': 'The clearance in liters/hour of relebactam from the plasma of critically ill patients receiving ECMO.', 'unitOfMeasure': 'Liters per hour', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Imipenem Area Under the Curve (AUC)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Imipenem-Cilastatin-Relebactam', 'description': 'Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.\n\nImipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.'}], 'classes': [{'categories': [{'measurements': [{'value': '36.9', 'spread': '13.3', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).', 'description': 'The AUC in milligram\\*hour/liter of imipenem calculated from concentrations collected between zero and 6 hours at steady-state', 'unitOfMeasure': 'mg*h/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Relebactam Area Under the Curve (AUC)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Imipenem-Cilastatin-Relebactam', 'description': 'Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.\n\nImipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.'}], 'classes': [{'categories': [{'measurements': [{'value': '45.3', 'spread': '33.2', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).', 'description': 'The AUC in milligram\\*hour/liter of relebactam calculated from concentrations collected between zero and 6 hours at steady-state', 'unitOfMeasure': 'mg*h/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Imipenem-Cilastatin-Relebactam', 'description': 'Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.\n\nImipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Imipenem-Cilastatin-Relebactam', 'description': 'Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.\n\nImipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '7', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '50', 'spread': '16', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '5', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '4', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '7', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2021-07-07', 'size': 407539, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2024-02-20T12:32', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 8}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-01-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-08', 'completionDateStruct': {'date': '2023-06-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-08-01', 'studyFirstSubmitDate': '2020-07-27', 'resultsFirstSubmitDate': '2024-02-20', 'studyFirstSubmitQcDate': '2020-07-27', 'lastUpdatePostDateStruct': {'date': '2024-08-07', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2024-08-01', 'studyFirstPostDateStruct': {'date': '2020-07-30', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2024-08-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-05-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Imipenem Clearance', 'timeFrame': '6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).', 'description': 'The clearance in liters/hour of imipenem from the plasma of critically ill patients receiving ECMO.'}, {'measure': 'Relebactam Clearance', 'timeFrame': '6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).', 'description': 'The clearance in liters/hour of relebactam from the plasma of critically ill patients receiving ECMO.'}], 'secondaryOutcomes': [{'measure': 'Imipenem Area Under the Curve (AUC)', 'timeFrame': '6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).', 'description': 'The AUC in milligram\\*hour/liter of imipenem calculated from concentrations collected between zero and 6 hours at steady-state'}, {'measure': 'Relebactam Area Under the Curve (AUC)', 'timeFrame': '6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).', 'description': 'The AUC in milligram\\*hour/liter of relebactam calculated from concentrations collected between zero and 6 hours at steady-state'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['beta-lactam', 'pharmacokinetics'], 'conditions': ['Sepsis']}, 'descriptionModule': {'briefSummary': "Extracorporeal membrane oxygenation (ECMO) is a from of cardiopulmonary life-support for critically ill patients where blood is extracted from the vascular system and circulated by a mechanical pump while it is oxygenated and re-infused into the patient's circulation. It is well known that critically ill patients may experience alterations in antibiotic pharmacokinetics, and as a result, dosing modifications are generally required. There is a need to understand how ECMO circuits affect the pharmacokinetics and disposition of drugs. This study is designed to assess the pharmacokinetics of the new broad-spectrum antibiotic, imipenem-cilastatin-relebactam, in critically ill patients receiving ECMO.", 'detailedDescription': 'This is a single center, open-label study to determine imipenem-cilastatin-relebactam pharmacokinetics in critically ill patients receiving ECMO. Eight patients with suspected suspected sepsis and who are receiving ECMO will be enrolled. Each participant will receive four to six doses of imipenem-cilastatin-relebactam according to current approved prescribing information, followed by ten blood samples to determine concentrations. Non-compartmental and population pharmacokinetic analyses will be determined to assess the effects of ECMO on imipenem and relebactam pharmacokinetic parameters.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age 18 years or older;\n* On support with Veno-venous- or Veno-arterial-ECMO;\n* Documented infection or presumed infection as confirmed by the presence of at least one of the following criteria within the past 72 hours:\n\n * Documented fever (oral, rectal, tympanic, or core temperature \\> 38.5° C)\n * Hypothermia (oral, rectal, tympanic, or core temperature \\< 35.0° C)\n * An elevated white blood cell (WBC) count ≥ 12,000 cells/mm3\n\nExclusion Criteria:\n\n* If female, currently pregnant or breast feeding;\n* History of any moderate or severe hypersensitivity or allergic reaction to any β-lactam agent (a history of mild rash to a β-lactam followed by uneventful re-exposure is not a contraindication);\n* Severe renal dysfunction defined as a creatinine clearance \\< 15 mL/min (calculated by the Cockcroft-Gault equation using actual body weight) or requirement for continuous renal replacement therapy or hemodialysis;\n* Hemoglobin less than 8 mg/dL at baseline;\n* Use of probenecid, valproic acid, or imipenem within 3 days before study drug infusion;\n* Acute liver injury, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \\> 5 times the upper limit of normal, or AST or ALT \\> 3 times the upper limit of normal with an associated total bilirubin \\> 2 times upper limit of normal;\n* Any rapidly-progressing disease or immediately life-threatening illness (defined as imminent death within 48 hours in the opinion of the investigator);\n* Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of study data;\n* Planned or prior participation in any other interventional drug study within 30 days.'}, 'identificationModule': {'nctId': 'NCT04493151', 'briefTitle': 'Imipenem/Cilastatin/Relebactam PK in ECMO', 'organization': {'class': 'OTHER', 'fullName': 'Hartford Hospital'}, 'officialTitle': 'Pharmacokinetics of Imipenem/Cilastatin/Relebactam in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (ECMO)', 'orgStudyIdInfo': {'id': '59752'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Imipenem-Cilastatin-Relebactam', 'description': 'Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.', 'interventionNames': ['Drug: Imipenem, Cilastatin and Relebactam']}], 'interventions': [{'name': 'Imipenem, Cilastatin and Relebactam', 'type': 'DRUG', 'otherNames': ['Recarbrio'], 'description': 'After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.', 'armGroupLabels': ['Imipenem-Cilastatin-Relebactam']}]}, 'contactsLocationsModule': {'locations': [{'zip': '06102', 'city': 'Hartford', 'state': 'Connecticut', 'country': 'United States', 'facility': 'Hartford Hospital', 'geoPoint': {'lat': 41.76371, 'lon': -72.68509}}], 'overallOfficials': [{'name': 'Joseph L Kuti, PharmD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Hartford Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Joseph L. Kuti, PharmD', 'class': 'OTHER'}, 'collaborators': [{'name': 'Merck Sharp & Dohme LLC', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Associate Director, Center for Anti-Infective Research and Development', 'investigatorFullName': 'Joseph L. Kuti, PharmD', 'investigatorAffiliation': 'Hartford Hospital'}}}}