Clinical Trials to Reduce the Risk of Antimicrobial Resistance
NCT ID: NCT01570192
Last Updated: 2017-09-29
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
43 participants
INTERVENTIONAL
2010-09-30
2015-04-30
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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IV meropenem; parenteral aminoglycoside
Subjects assigned to this group will receive:
* IV meropenem (2 g infused over 3 hrs q 8 hr);
* a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
* tobramycin nebulization
Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat potential Gram-positive pathogens.
IV meropenem
Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
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
a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomycin (per institutional guidelines) will be available for MRSA coverage.
Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization
tobramycin nebulization 600mg/day
I.V. Meropenem
Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage to treat Gram-positive pathogens.
\*\*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.
I.V. Meropenem
Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage
Linezolid or Vancomycin (per institutional guidelines) will be available for MRSA coverage.
Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
Interventions
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IV meropenem
Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
I.V. Meropenem
Subjects assigned to this group will receive IV meropenem (2 g infused over 3 hrs q 8 hr).
Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage
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
a parenteral aminoglycoside (tobramycin or gentamicin-5mg/kg IV Q24h or amikacin 20 mg/kg IV Q24h)
Linezolid or Vancomycin (per institutional guidelines) will be available for MRSA coverage.
Linezolid or vancomycin (per institutional guidelines) will be available for MRSA coverage.
tobramycin nebulization
tobramycin nebulization 600mg/day
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
Hospitalized males or females ≥ 18 yrs with respiratory failure requiring mechanical ventilation and clinical suspicion of HABP, HCAP or VABP.
Onset 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
Women of childbearing potential if their pregnancy test is negative
Subjects 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.)
Patients should have clinical findings that support a diagnosis of HABP/VABP/HCAP:
Within 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
Within 36 hours before the start of empiric study therapy, a quantitative culture of Bronchoscopic BAL fluid must be obtained.
Patients with VABP should have a Clinical Pulmonary Infection Score of \>/= 5.
Exclusion Criteria
Subjects with contra-indications to ANY study medication, in particular with known or suspected allergy or hypersensitivity.
Women who are pregnant or lactating.
Subjects 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.
Subjects with known or suspected community acquired bacterial pneumonia (CABP) or viral pneumonia; or Subjects with acute exacerbation of chronic bronchitis without evidence of pneumonia.
Subjects with primary lung cancer or another malignancy metastatic to the lungs.
Subjects who were previously enrolled in this study.
Subjects who have had an investigational drug or have used an investigational device within 30 days prior to entering the study.
Subjects with another focus of infection requiring concurrent antibiotics that would interfere with evaluation of the response to study drug.
Subjects with cystic fibrosis, AIDS with a CD4 lymphocyte count \<200 cells/µl, neutropenia (absolute neutrophil count \<500 cells/ml), known or suspected active tuberculosis.
Subjects with little chance of survival for the duration of study therapy.
Subjects with an APACHE II score \>35.
Subjects with underlying condition(s) which would make it difficult to interpret response to the study drugs.
Subjects 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.
Subjects who have undergone bone marrow transplantation.
Subjects with profound hypoxia as defined by a PaO2/FiO2 ratio \<100.
18 Years
ALL
No
Sponsors
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University of Florida
OTHER
Responsible Party
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Principal Investigators
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George L Drusano, MD
Role: PRINCIPAL_INVESTIGATOR
University of Florida
Locations
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InClin, Inc.
San Mateo, California, United States
UFL Department of Medicine: Pulmonary, Critical Care and Sleep Medicine
Gainesville, Florida, United States
Emory University
Atlanta, Georgia, United States
Northwestern University
Chicago, Illinois, United States
JMI Laboratories
North Liberty, Iowa, United States
Washington University in St. Louis School of Medicine
St Louis, Missouri, United States
Weill Cornell Medical Center of Cornell University
New York, New York, United States
Cleveland Clinic Lerner College of Medicine
Cleveland, Ohio, United States
Institut de Cardiologie, Groupe Hospitalier Pitie-Salpetriere
Paris, , France
Hannover Clinical Trial Center GmbH
Hanover, , Germany
Hospital Vall d'Hebron
Barcelona, , Spain
Countries
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References
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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.
Other Identifiers
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10-0060
Identifier Type: -
Identifier Source: org_study_id