Ignite Creation Date:
2025-12-24 @ 3:54 PM
Ignite Modification Date:
2025-12-27 @ 4:17 PM
Study NCT ID:
NCT01570192
Status:
TERMINATED
Last Update Posted:
2017-09-29
First Post:
2012-03-22
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Clinical Trials to Reduce the Risk of Antimicrobial Resistance
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018410', 'term': 'Pneumonia, Bacterial'}, {'id': 'D011552', 'term': 'Pseudomonas Infections'}], 'ancestors': [{'id': 'D001424', 'term': 'Bacterial Infections'}, {'id': 'D001423', 'term': 'Bacterial Infections and Mycoses'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D011014', 'term': 'Pneumonia'}, {'id': 'D012141', 'term': 'Respiratory Tract Infections'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D016905', 'term': 'Gram-Negative Bacterial Infections'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077731', 'term': 'Meropenem'}, {'id': 'D014031', 'term': 'Tobramycin'}, {'id': 'D000069349', 'term': 'Linezolid'}, {'id': 'D014640', 'term': 'Vancomycin'}], 'ancestors': [{'id': 'D013845', 'term': 'Thienamycins'}, {'id': 'D015780', 'term': 'Carbapenems'}, {'id': 'D047090', 'term': 'beta-Lactams'}, {'id': 'D007769', 'term': 'Lactams'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D009328', 'term': 'Nebramycin'}, {'id': 'D007612', 'term': 'Kanamycin'}, {'id': 'D000617', 'term': 'Aminoglycosides'}, {'id': 'D006027', 'term': 'Glycosides'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D000081', 'term': 'Acetamides'}, {'id': 'D000085', 'term': 'Acetates'}, {'id': 'D000144', 'term': 'Acids, Acyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D023303', 'term': 'Oxazolidinones'}, {'id': 'D010080', 'term': 'Oxazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006020', 'term': 'Glycopeptides'}, {'id': 'D006001', 'term': 'Glycoconjugates'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'gdrusano@ufl.edu', 'phone': '407-313-7060', 'title': 'Dr. George L. Drusano', 'organization': 'University of Florida, Department of Medicine'}, 'certainAgreement': {'restrictionType': 'GT60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'IV Meropenem; Parenteral Aminoglycoside', 'description': 'Subjects assigned to this group will receive:\n\n* IV meropenem (2 g infused over 3 hrs q 8 hr);\n* a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)\n* tobramycin nebulization\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat potential Gram-positive pathogens.\n\nIV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nParenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24h: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)\n\nLinezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.\n\ntobramycin nebulization: tobramycin nebulization 600mg/day', 'otherNumAtRisk': 13, 'otherNumAffected': 0, 'seriousNumAtRisk': 13, 'seriousNumAffected': 6}, {'id': 'EG001', 'title': 'I.V. Meropenem', 'description': "Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat Gram-positive pathogens.\n\n\\*\\*NOTE: Empiric MRSA coverage is allowed in both arms. This therapy is advised for any subjects with known or suspected MRSA entering the study. Once microbiologic results are available, this coverage may be discontinued at the investigator's discretion.\n\nI.V. Meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage\n\nLinezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.", 'otherNumAtRisk': 30, 'otherNumAffected': 0, 'seriousNumAtRisk': 30, 'seriousNumAffected': 11}], 'seriousEvents': [{'term': 'cutaneous eruption', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'reinforced duodenal ulcer', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'pneomonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'cardiogenic shock', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'cardiac arrest', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'COPD with acute exacerbation', 'notes': 'Note: this patient in group 2 (IV mero only) experienced 2 SAES that occurred in separate organ systems: AICD fired/NSTEMI and COPD with acute exacerbation. Therefore, this patient was counted twice.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders'}, {'term': 'pneumothorax', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders'}, {'term': 'AICD fired/NSTEMI', 'notes': 'Note: this patient in group 2 (IV mero only) experienced 2 SAES that occurred in separate organ systems: AICD fired/NSTEMI and COPD with acute exacerbation. Therefore, this patient was counted twice.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders'}, {'term': 'PEA arrest', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders'}, {'term': 'multi-organ failure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'General disorders'}, {'term': 'multi-organ failure due to distributive and cardiogenic shock', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders'}, {'term': 'stroke', 'notes': 'Note: this patient in group 2 (IV mero only) experienced 2 SAES that occurred in separate organ systems: Pulmonary embolism and stroke.. Therefore, this patient was counted twice.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'pulmonary embolism', 'notes': 'Note: this patient in group 2 (IV mero only) experienced 2 SAES that occurred in separate organ systems: Pulmonary embolism and stroke. Therefore, this patient was counted twice.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'refractory shock', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'septic shock', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'cardiorespiratory arrest', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Participants With Suppression and Emergence of Resistance', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'IV Meropenem; Parenteral Aminoglycoside', 'description': 'Subjects assigned to this group will receive:\n\n* IV meropenem (2 g infused over 3 hrs q 8 hr);\n* a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)\n* tobramycin nebulization\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat potential Gram-positive pathogens.\n\nIV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nParenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24h: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)\n\nLinezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.\n\ntobramycin nebulization: tobramycin nebulization 600mg/day'}, {'id': 'OG001', 'title': 'I.V. Meropenem', 'description': "Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat Gram-positive pathogens.\n\n\\*\\*NOTE: Empiric MRSA coverage is allowed in both arms. This therapy is advised for any subjects with known or suspected MRSA entering the study. Once microbiologic results are available, this coverage may be discontinued at the investigator's discretion.\n\nI.V. Meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage\n\nLinezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage."}], 'classes': [{'title': 'suppression of emergence of resistance', 'categories': [{'measurements': [{'value': '5', 'groupId': 'OG001'}]}]}, {'title': 'emergence of resistance', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'up to 28 days after enrollment', 'description': 'The emergence of resistance is defined as a change of meropenem MIC or aminoglycoside MIC by two tube dilutions (fourfold) from baseline when assessed at the second BAL procedure on day 5/early extubation. Patients are evaluable for this endpoint IF they had baseline BAL and Day 5/early extubation and if they had positive cultures on baseline and Day/EE.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients in the ME population with BAL at baseline and at Day 5/EE and pathogens collected at baseline BAL and at Day 5/EE BAL.'}, {'type': 'SECONDARY', 'title': 'Clinical Response', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}, {'value': '6', 'groupId': 'OG002'}, {'value': '18', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'ME Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population'}, {'id': 'OG001', 'title': 'MEGroup - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population.'}, {'id': 'OG002', 'title': 'm-MITT Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}, {'id': 'OG003', 'title': 'm-MITT Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}], 'classes': [{'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}, {'value': '2', 'groupId': 'OG002'}, {'value': '8', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'End of treatment - up to 28 days after enrollment', 'description': 'Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.'}, {'type': 'SECONDARY', 'title': 'Clinical Response in Subjects Who Received Prior Antibiotics', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}, {'value': '4', 'groupId': 'OG002'}, {'value': '6', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'ME Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population'}, {'id': 'OG001', 'title': 'ME Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population.'}, {'id': 'OG002', 'title': 'm-MITT Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}, {'id': 'OG003', 'title': 'm-MITT Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}, {'value': '1', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'End of treatment - up to 28 days after enrollment', 'description': 'Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.'}, {'type': 'SECONDARY', 'title': 'Overall Microbiologic Response', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}, {'value': '6', 'groupId': 'OG002'}, {'value': '18', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'ME Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population'}, {'id': 'OG001', 'title': 'ME Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population.'}, {'id': 'OG002', 'title': 'm-MITT Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}, {'id': 'OG003', 'title': 'm-MITT Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}], 'classes': [{'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '2', 'groupId': 'OG002'}, {'value': '7', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'End of treatment - up to 28 days after enrollment', 'description': 'Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.'}, {'type': 'SECONDARY', 'title': 'Pretreatment Pathogen Response', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}, {'value': '6', 'groupId': 'OG002'}, {'value': '18', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'ME Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population'}, {'id': 'OG001', 'title': 'ME Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population.'}, {'id': 'OG002', 'title': 'm-MITT Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}, {'id': 'OG003', 'title': 'm-MITT Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}], 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '9', 'groupId': 'OG001'}, {'value': '3', 'groupId': 'OG002'}, {'value': '11', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'End of treatment - up to 28 days after enrollment', 'description': 'Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.'}, {'type': 'SECONDARY', 'title': 'Suppression of the Emergence of Resistance in Other Gram-negative Pathogens', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '1', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'ME Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population'}, {'id': 'OG001', 'title': 'ME Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population.'}, {'id': 'OG002', 'title': 'm-MITT Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}, {'id': 'OG003', 'title': 'm-MITT Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '1', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Day 5/Early Extubation', 'description': 'Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.'}, {'type': 'SECONDARY', 'title': 'Occurrence of Repeat Negative Cultures', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}, {'value': '4', 'groupId': 'OG002'}, {'value': '17', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'ME Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population'}, {'id': 'OG001', 'title': 'ME Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population.'}, {'id': 'OG002', 'title': 'm-MITT Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}, {'id': 'OG003', 'title': 'm-MITT Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}], 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '3', 'groupId': 'OG002'}, {'value': '7', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Day 5/Early Extubation', 'description': 'Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.'}, {'type': 'SECONDARY', 'title': 'Mortality', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}, {'value': '6', 'groupId': 'OG002'}, {'value': '18', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'ME Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population'}, {'id': 'OG001', 'title': 'ME Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population.'}, {'id': 'OG002', 'title': 'm-MITT Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}, {'id': 'OG003', 'title': 'm-MITT Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '2', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '14 days', 'description': 'Percentage of patients who died by efficacy endpoint, treatment group and population (n/N)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.'}, {'type': 'SECONDARY', 'title': 'Mortality', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}, {'value': '6', 'groupId': 'OG002'}, {'value': '18', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'ME Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population'}, {'id': 'OG001', 'title': 'ME Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologic Evaluable (ME) group and population.'}, {'id': 'OG002', 'title': 'm-MITT Group - Meropenem Plus Aminoglycoside', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}, {'id': 'OG003', 'title': 'm-MITT Group - Meropenem Only', 'description': 'Percentage of patients with successful responses by efficacy endpoint, Microbiologically modified ITT (m-MITT) group and population.'}], 'classes': [{'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '3', 'groupId': 'OG002'}, {'value': '3', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '28 days', 'description': 'Percentage of patients who died by efficacy endpoint, treatment group and population (n/N)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'The ME population, 19 subjects were analyzed and the m-MITT population, 24 were analyzed. Not all subjects were evaluable for each endpoint.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'IV Meropenem; Parenteral Aminoglycoside', 'description': 'Subjects assigned to this group will receive:\n\n* IV meropenem (2 g infused over 3 hrs q 8 hr);\n* a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)\n* tobramycin nebulization\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat potential Gram-positive pathogens.\n\nIV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nParenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24h: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)\n\nLinezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.\n\ntobramycin nebulization: tobramycin nebulization 600mg/day'}, {'id': 'FG001', 'title': 'I.V. Meropenem', 'description': "Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat Gram-positive pathogens.\n\n\\*\\*NOTE: Empiric MRSA coverage is allowed in both arms. This therapy is advised for any subjects with known or suspected MRSA entering the study. Once microbiologic results are available, this coverage may be discontinued at the investigator's discretion.\n\nI.V. Meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage\n\nLinezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage."}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}, {'groupId': 'FG001', 'numSubjects': '30'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '17'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}, {'groupId': 'FG001', 'numSubjects': '13'}]}], 'dropWithdraws': [{'type': 'no qualifying organism', 'reasons': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'changed to palliative care', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Physician Decision', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'We had 8 clinical sites: recruitment into the study began September 2010 and ended April 10, 2015.', 'preAssignmentDetails': 'Enrolled participants were excluded from the trial before assignment to groups because participants had no qualifying organisms; this includes participants with no growth on screening BAL, those with \\< 104 CFU/mL on BAL, and those with only Gram-positive bacteria cultured from the BAL.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'BG000'}, {'value': '30', 'groupId': 'BG001'}, {'value': '43', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'IV Meropenem; Parenteral Aminoglycoside', 'description': 'Subjects assigned to this group will receive:\n\n* IV meropenem (2 g infused over 3 hrs q 8 hr);\n* a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)\n* tobramycin nebulization\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat potential Gram-positive pathogens.\n\nIV meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nParenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24h: a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)\n\nLinezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.\n\ntobramycin nebulization: tobramycin nebulization 600mg/day'}, {'id': 'BG001', 'title': 'I.V. Meropenem', 'description': "Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat Gram-positive pathogens.\n\n\\*\\*NOTE: Empiric MRSA coverage is allowed in both arms. This therapy is advised for any subjects with known or suspected MRSA entering the study. Once microbiologic results are available, this coverage may be discontinued at the investigator's discretion.\n\nI.V. Meropenem: Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage\n\nLinezolid or Vancomcin (per institutional guidelines) will be available for MRSA coverage.: Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage."}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '20', 'groupId': 'BG001'}, {'value': '26', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '17', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '61.2', 'spread': '18.3', 'groupId': 'BG000'}, {'value': '58.4', 'spread': '12.6', 'groupId': 'BG001'}, {'value': '59.2', 'spread': '14.4', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '13', 'groupId': 'BG001'}, {'value': '20', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '17', 'groupId': 'BG001'}, {'value': '23', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '18', 'groupId': 'BG001'}, {'value': '29', 'groupId': 'BG002'}]}]}, {'title': 'France', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '13', 'groupId': 'BG002'}]}]}, {'title': 'Spain', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Baseline acute physiology and chronic health evaluation II (APACHE II) score', 'classes': [{'categories': [{'measurements': [{'value': '22.6', 'spread': '4.6', 'groupId': 'BG000'}, {'value': '21.0', 'spread': '6.2', 'groupId': 'BG001'}, {'value': '21.5', 'spread': '5.8', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': "A severity of disease classification system applied within 24 hours of patient admission to an ICU. The point score is calculated from a patient's age and physiological measurements. The range of score is between 0-71. Physiological measurements and all ages fit into that range. Note: the higher the score, the higher the probability of death.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}], 'populationDescription': 'Number of patients enrolled in the study and who had a baseline BAL.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR'], 'maskingDescription': 'This is an open-label study with 1:1 randomization between two active treatment groups.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 43}}, 'statusModule': {'whyStopped': 'NIAID terminated the study due to low subject enrollment', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2010-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-09', 'dispFirstSubmitDate': '2016-03-15', 'completionDateStruct': {'date': '2015-04', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-09-01', 'studyFirstSubmitDate': '2012-03-22', 'dispFirstSubmitQcDate': '2016-03-15', 'resultsFirstSubmitDate': '2016-12-22', 'studyFirstSubmitQcDate': '2012-03-30', 'dispFirstPostDateStruct': {'date': '2016-04-15', 'type': 'ESTIMATED'}, 'lastUpdatePostDateStruct': {'date': '2017-09-29', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-03-08', 'studyFirstPostDateStruct': {'date': '2012-04-04', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2017-04-20', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2015-04', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Participants With Suppression and Emergence of Resistance', 'timeFrame': 'up to 28 days after enrollment', 'description': 'The emergence of resistance is defined as a change of meropenem MIC or aminoglycoside MIC by two tube dilutions (fourfold) from baseline when assessed at the second BAL procedure on day 5/early extubation. Patients are evaluable for this endpoint IF they had baseline BAL and Day 5/early extubation and if they had positive cultures on baseline and Day/EE.'}], 'secondaryOutcomes': [{'measure': 'Clinical Response', 'timeFrame': 'End of treatment - up to 28 days after enrollment', 'description': 'Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)'}, {'measure': 'Clinical Response in Subjects Who Received Prior Antibiotics', 'timeFrame': 'End of treatment - up to 28 days after enrollment', 'description': 'Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)'}, {'measure': 'Overall Microbiologic Response', 'timeFrame': 'End of treatment - up to 28 days after enrollment', 'description': 'Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)'}, {'measure': 'Pretreatment Pathogen Response', 'timeFrame': 'End of treatment - up to 28 days after enrollment', 'description': 'Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)'}, {'measure': 'Suppression of the Emergence of Resistance in Other Gram-negative Pathogens', 'timeFrame': 'Day 5/Early Extubation', 'description': 'Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)'}, {'measure': 'Occurrence of Repeat Negative Cultures', 'timeFrame': 'Day 5/Early Extubation', 'description': 'Percentage of patients with successful responses by efficacy endpoint, treatment group and population (n/N)'}, {'measure': 'Mortality', 'timeFrame': '14 days', 'description': 'Percentage of patients who died by efficacy endpoint, treatment group and population (n/N)'}, {'measure': 'Mortality', 'timeFrame': '28 days', 'description': 'Percentage of patients who died by efficacy endpoint, treatment group and population (n/N)'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['gram negative pathogens', 'Pseudomonas aeruginosa', 'Acinetobacter', 'HCAP', 'VABP', 'HABP'], 'conditions': ['Bacterial Pneumonia']}, 'referencesModule': {'references': [{'pmid': '8630626', 'type': 'BACKGROUND', 'citation': 'Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies. A consensus statement, American Thoracic Society, November 1995. Am J Respir Crit Care Med. 1996 May;153(5):1711-25. doi: 10.1164/ajrccm.153.5.8630626. No abstract available.'}, {'type': 'BACKGROUND', 'citation': 'Bauernfeind A, Jungwirth R. In Vitro Activity of SM 7338 and Imipenem. 28th ICAAC, Los Angeles, October 1988. Abstract 599'}, {'pmid': '3886144', 'type': 'BACKGROUND', 'citation': 'Calandra GB, Hesney M, Brown KR. Imipenem/cilastatin therapy of serious infections: a U.S. multicenter noncomparative trial. Clin Ther. 1985;7(2):225-38.'}, {'type': 'BACKGROUND', 'citation': 'Clarke AM, Zemcov SJV. SM 7338 (ICI 194,660), A New DHP-1 Stable Carbapenem; In Vitro Activity Against a Wide Range of Canadian Clinical Isolates. 28th ICAAC, Los Angeles, October 1988. Abstract 598.'}, {'pmid': '9455502', 'type': 'BACKGROUND', 'citation': 'Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. 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SM 7338, A New Carbapenem Antibacterial: In Vitro Activity Against Bacterial Strains of Clinical Origins. 27th ICAAC, New York, October 1987, Abstract 755.'}, {'pmid': '2655530', 'type': 'BACKGROUND', 'citation': 'Edwards JR, Turner PJ, Wannop C, Withnell ES, Grindey AJ, Nairn K. In vitro antibacterial activity of SM-7338, a carbapenem antibiotic with stability to dehydropeptidase I. Antimicrob Agents Chemother. 1989 Feb;33(2):215-22. doi: 10.1128/AAC.33.2.215.'}, {'pmid': '8315120', 'type': 'BACKGROUND', 'citation': 'Fagon JY, Chastre J, Novara A, Medioni P, Gibert C. Characterization of intensive care unit patients using a model based on the presence or absence of organ dysfunctions and/or infection: the ODIN model. Intensive Care Med. 1993;19(3):137-44. doi: 10.1007/BF01720528.'}, {'pmid': '8203853', 'type': 'BACKGROUND', 'citation': 'Fink MP, Snydman DR, Niederman MS, Leeper KV Jr, Johnson RH, Heard SO, Wunderink RG, Caldwell JW, Schentag JJ, Siami GA, et al. 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Abstract 597.'}, {'type': 'BACKGROUND', 'citation': 'Kayser FH, Morenzoni G. Activity of SM 7338, A New Carbapenem Antibacterial Against Gram-Positive Bacteria. 28th ICAAC, Los Angeles, October 1988. Abstract 603.'}, {'pmid': '10027448', 'type': 'BACKGROUND', 'citation': 'Kollef MH, Sherman G, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999 Feb;115(2):462-74. doi: 10.1378/chest.115.2.462.'}, {'pmid': '7497777', 'type': 'BACKGROUND', 'citation': 'Kollef MH, Silver P, Murphy DM, Trovillion E. The effect of late-onset ventilator-associated pneumonia in determining patient mortality. Chest. 1995 Dec;108(6):1655-62. doi: 10.1378/chest.108.6.1655.'}, {'type': 'BACKGROUND', 'citation': 'Lancero MG, Young LS. In Vitro Studies with SM 7338; A Novel Carbapenem with Broad Bactericidal Activity. 28th ICAAC, Los Angeles, October 1988. 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Nosocomial repiratory infections. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious disease. Philadelphia: Churchill Livingstone, 2000: 3021-3026.'}, {'type': 'BACKGROUND', 'citation': "Sumita Y, Fukasawa M, Okunda T. SM 7338, A New Carbapenem Antibacterial: Affinities for PBP's and Morphological Changes. 27th ICAAC, New York, October 1987. Abstract 756."}, {'type': 'BACKGROUND', 'citation': 'Sumita Y, Inoue M, Mitsuhashi S. In Vitro Antibacterial Activity of SM 7338. 28th ICAAC, Los Angeles, October 1988. Abstract 600.'}, {'type': 'BACKGROUND', 'citation': 'Sunagawa M, Matsumura H, Inoue T, et al. SM 7338, A New Carbapenem Antibacterial: Structure-Activity Relations and Physiochemical Properties. 27th ICAAC, New York, October 1987. Abstract 752.'}, {'pmid': '14258517', 'type': 'BACKGROUND', 'citation': 'TALKE H, SCHUBERT GE. [ENZYMATIC UREA DETERMINATION IN THE BLOOD AND SERUM IN THE WARBURG OPTICAL TEST]. Klin Wochenschr. 1965 Feb 1;43:174-5. doi: 10.1007/BF01484513. No abstract available. German.'}, {'pmid': '2202245', 'type': 'BACKGROUND', 'citation': 'Torres A, Aznar R, Gatell JM, Jimenez P, Gonzalez J, Ferrer A, Celis R, Rodriguez-Roisin R. Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis. 1990 Sep;142(3):523-8. doi: 10.1164/ajrccm/142.3.523.'}, {'pmid': '11083889', 'type': 'BACKGROUND', 'citation': 'Torres A, Bauer TT, Leon-Gil C, Castillo F, Alvarez-Lerma F, Martinez-Pellus A, Leal-Noval SR, Nadal P, Palomar M, Blanquer J, Ros F. Treatment of severe nosocomial pneumonia: a prospective randomised comparison of intravenous ciprofloxacin with imipenem/cilastatin. Thorax. 2000 Dec;55(12):1033-9. doi: 10.1136/thorax.55.12.1033.'}, {'pmid': '9476869', 'type': 'BACKGROUND', 'citation': 'Trouillet JL, Chastre J, Vuagnat A, Joly-Guillou ML, Combaux D, Dombret MC, Gibert C. Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. Am J Respir Crit Care Med. 1998 Feb;157(2):531-9. doi: 10.1164/ajrccm.157.2.9705064.'}, {'type': 'BACKGROUND', 'citation': "Vetter N. The Use of Meropenem ('Merrem'/'Meronen') in the Therapy of Hospital-acquired Lower Respiratory Infections: a Review of Clinical Experience. 18th International Congress of Chemotherapy, Stockholm, Sweden, 27 June-2 July, 1993. Abstract 70."}, {'type': 'BACKGROUND', 'citation': 'Wise R, Andrews JM, Ashby JP. The Bactericidal Activity of the Carbapenem, SM 7338, Alone and in Combination. 28th ICAAC, Los Angeles, October 1988. Abstract 605.'}, {'type': 'BACKGROUND', 'citation': 'World Health Organization. Draft Global Strategy for the Containment of Antimicrobial Resistance. Available on the Internet at http://www.who.int/emc/amr.htm'}, {'pmid': '29038277', 'type': 'DERIVED', 'citation': 'Drusano GL, Corrado ML, Girardi G, Ellis-Grosse EJ, Wunderink RG, Donnelly H, Leeper KV, Brown M, Malek T, Hite RD, Ferrari M, Djureinovic D, Kollef MH, Mayfield L, Doyle A, Chastre J, Combes A, Walsh TJ, Dorizas K, Alnuaimat H, Morgan BE, Rello J, Mazo CA, Jones RN, Flamm RK, Woosley L, Ambrose PG, Bhavnani S, Rubino CM, Bulik CC, Louie A, Vicchiarelli M, Berman C. Dilution Factor of Quantitative Bacterial Cultures Obtained by Bronchoalveolar Lavage in Patients with Ventilator-Associated Bacterial Pneumonia. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01323-17. doi: 10.1128/AAC.01323-17. Print 2018 Jan.'}]}, 'descriptionModule': {'briefSummary': 'The primary objective of this study is to demonstrate a low rate of emergence of antibiotic resistance in P. aeruginosa and Acinetobacter spp during the treatment of hospitalized patients with pneumonia requiring mechanical ventilation treated with PD optimized meropenem administered as a prolonged infusion in combination with a parenteral aminoglycoside plus tobramycin by inhalation (Group 1) compared to therapy with meropenem alone (Group 2 - control arm).', 'detailedDescription': 'The goal of this clinical study is to demonstrate that the application of pharmacodynamic dosing principles to the antibiotic treatment of hospitalized subjects with culture-documented pneumonia (including HABP, VABP and HCAP) requiring mechanical ventilation can inhibit the emergence of antibiotic-resistant organisms during treatment and therefore may improve the rate of a satisfactory clinical response. Antibiotic resistance is defined as an increase in meropenem or aminoglycoside MIC by two tube dilutions (fourfold) from baseline. In animal models of infection, the pharmacodynamic driver for bactericidal effect by β lactam antibiotics such as meropenem is the proportion of the dosing interval during which plasma drug levels are maintained above the MIC of the causative pathogen. The hypothesis of this study is that prolongation of time above MIC by increasing total meropenem dose and the duration of infusion will counter-select for the emergence of antimicrobial resistance during the treatment of hospitalized subjects with pneumonia (i.e. HABP, VABP and HCAP) caused by P.aeruginosa, Acinetobacter species (spp), or other pathogens with intermediate susceptibility to meropenem, and that the addition of parenteral aminoglycosides (amikacin, tobramycin or gentamicin) and nebulized aminoglycoside (tobramycin) given along optimal pharmacodynamic principles will further reduce the likelihood of resistance emergence, particularly among the non-fermenting Gram-negative bacilli, such as Pseudomonas aeruginosa and Acinetobacter spp. The observed incidence of resistance emergence to meropenem will be compared across therapeutic regimens.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion criteria:\n\nWritten informed consent by the subject/subject's LAR.\n\nHospitalized males or females ≥ 18 yrs with respiratory failure requiring mechanical ventilation and clinical suspicion of HABP, HCAP or VABP.\n\nOnset or exacerbation of pneumonia at least 48 hours after admission to any patient health care facility or onset of pneumonia in a nursing home or rehabilitation facility with subsequent transfer to an acute care facility\n\nWomen of childbearing potential if their pregnancy test is negative\n\nSubjects who have received previous antibacterial therapy within 14 days of pre-treatment bronchoscopy entry may be entered only if the subject has not responded clinically.). While less than 24 hours of pre-treatment antibiotics is preferential, recovery of \\>104 CFU/ml in the quantitative Bronchoscopic BAL will be seen as primary evidence that the prior therapy was not efficacious and enrollment will be allowed.)\n\nPatients should have clinical findings that support a diagnosis of HABP/VABP/HCAP:\n\nWithin 48 hours before starting empiric therapy a subject's chest radiograph should show the presence of a NEW or progressive infiltrate, cavitation, or effusion suggestive of pneumonia\n\nWithin 36 hours before the start of empiric study therapy, a quantitative culture of Bronchoscopic BAL fluid must be obtained.\n\nPatients with VABP should have a Clinical Pulmonary Infection Score of \\>/= 5.\n\nExclusion Criteria:\n\nSubjects with pneumonia caused by pathogens resistant to meropenem (MIC greater than or equal to 16µg/ml) or a prior meropenem therapy failure.\n\nSubjects with contra-indications to ANY study medication, in particular with known or suspected allergy or hypersensitivity.\n\nWomen who are pregnant or lactating.\n\nSubjects taking anticonvulsant medications for a known seizure disorder.Patients with a history of seizures, AND who are stabilized on anti-seizure medication, may be enrolled into the study at the discretion of the site investigator.\n\nSubjects with known or suspected community acquired bacterial pneumonia (CABP) or viral pneumonia; or Subjects with acute exacerbation of chronic bronchitis without evidence of pneumonia.\n\nSubjects with primary lung cancer or another malignancy metastatic to the lungs.\n\nSubjects who were previously enrolled in this study.\n\nSubjects who have had an investigational drug or have used an investigational device within 30 days prior to entering the study.\n\nSubjects with another focus of infection requiring concurrent antibiotics that would interfere with evaluation of the response to study drug.\n\nSubjects with cystic fibrosis, AIDS with a CD4 lymphocyte count \\<200 cells/µl, neutropenia (absolute neutrophil count \\<500 cells/ml), known or suspected active tuberculosis.\n\nSubjects with little chance of survival for the duration of study therapy.\n\nSubjects with an APACHE II score \\>35.\n\nSubjects with underlying condition(s) which would make it difficult to interpret response to the study drugs.\n\nSubjects with hypotension or acidosis despite attempts at fluid resuscitation. Subjects requiring ongoing treatment with vasopressors will be eligible for the study if their hypotension is controlled and acidosis has resolved. Subjects with intractable septic shock are not eligible for enrollment.\n\nSubjects who have undergone bone marrow transplantation.\n\nSubjects with profound hypoxia as defined by a PaO2/FiO2 ratio \\<100."}, 'identificationModule': {'nctId': 'NCT01570192', 'briefTitle': 'Clinical Trials to Reduce the Risk of Antimicrobial Resistance', 'organization': {'class': 'OTHER', 'fullName': 'University of Florida'}, 'officialTitle': 'Impact of Aggressive Empiric Antibiotic Therapy and Duration of Therapy on the Emergence of Antimicrobial Resistance During the Treatment of Hospitalized Subjects With Pneumonia Requiring Mechanical Ventilation', 'orgStudyIdInfo': {'id': '10-0060'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'IV meropenem; parenteral aminoglycoside', 'description': 'Subjects assigned to this group will receive:\n\n* IV meropenem (2 g infused over 3 hrs q 8 hr);\n* a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)\n* tobramycin nebulization\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat potential Gram-positive pathogens.', 'interventionNames': ['Drug: IV meropenem', 'Drug: Parenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24h', 'Drug: Linezolid or Vancomycin (per institutional guidelines) will be available for MRSA coverage.', 'Device: tobramycin nebulization']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'I.V. Meropenem', 'description': "Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat Gram-positive pathogens.\n\n\\*\\*NOTE: Empiric MRSA coverage is allowed in both arms. This therapy is advised for any subjects with known or suspected MRSA entering the study. Once microbiologic results are available, this coverage may be discontinued at the investigator's discretion.", 'interventionNames': ['Drug: I.V. Meropenem', 'Drug: Linezolid or Vancomycin (per institutional guidelines) will be available for MRSA coverage.']}], 'interventions': [{'name': 'IV meropenem', 'type': 'DRUG', 'otherNames': ['Merrem I.V.'], 'description': 'Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).', 'armGroupLabels': ['IV meropenem; parenteral aminoglycoside']}, {'name': 'I.V. Meropenem', 'type': 'DRUG', 'otherNames': ['Merrem I.V.'], 'description': 'Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).\n\nLinezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage', 'armGroupLabels': ['I.V. Meropenem']}, {'name': 'Parenteral aminoglycoside; tobramycin for injection USP OR gentamicin sulfate injection solution concentrate 5mg.kg IV q24h; amikacin sulfate injection USP 20 mg/kg IV q24h', 'type': 'DRUG', 'description': 'a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)', 'armGroupLabels': ['IV meropenem; parenteral aminoglycoside']}, {'name': 'Linezolid or Vancomycin (per institutional guidelines) will be available for MRSA coverage.', 'type': 'DRUG', 'description': 'Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.', 'armGroupLabels': ['I.V. Meropenem', 'IV meropenem; parenteral aminoglycoside']}, {'name': 'tobramycin nebulization', 'type': 'DEVICE', 'description': 'tobramycin nebulization 600mg/day', 'armGroupLabels': ['IV meropenem; parenteral aminoglycoside']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94403', 'city': 'San Mateo', 'state': 'California', 'country': 'United States', 'facility': 'InClin, Inc.', 'geoPoint': {'lat': 37.56299, 'lon': -122.32553}}, {'zip': '32610', 'city': 'Gainesville', 'state': 'Florida', 'country': 'United States', 'facility': 'UFL Department of Medicine: Pulmonary, Critical Care and Sleep Medicine', 'geoPoint': {'lat': 29.65163, 'lon': -82.32483}}, {'zip': '30322-4250', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'facility': 'Emory University', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '60611', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'Northwestern University', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '52317', 'city': 'North Liberty', 'state': 'Iowa', 'country': 'United States', 'facility': 'JMI Laboratories', 'geoPoint': {'lat': 41.74918, 'lon': -91.59795}}, {'zip': '63130', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'Washington University in St. Louis School of Medicine', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '10065', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Weill Cornell Medical Center of Cornell University', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '44195', 'city': 'Cleveland', 'state': 'Ohio', 'country': 'United States', 'facility': 'Cleveland Clinic Lerner College of Medicine', 'geoPoint': {'lat': 41.4995, 'lon': -81.69541}}, {'zip': 'Cedex 13', 'city': 'Paris', 'country': 'France', 'facility': 'Institut de Cardiologie, Groupe Hospitalier Pitie-Salpetriere', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'zip': '30625', 'city': 'Hanover', 'country': 'Germany', 'facility': 'Hannover Clinical Trial Center GmbH', 'geoPoint': {'lat': 52.37052, 'lon': 9.73322}}, {'zip': '08035', 'city': 'Barcelona', 'country': 'Spain', 'facility': "Hospital Vall d'Hebron", 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}], 'overallOfficials': [{'name': 'George L Drusano, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Florida'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Florida', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}