A Study of Plazomicin Compared with Colistin when combined with a second antibiotic (either meropenem or tigcycline) in the treatment of Patients with blood stream Infection (BSI) or nosocomial pneumonia due to Carbapenem-Resistant Enterobacteriaceae (CRE). Therapeutic Drug Managment (TDM) will be used to ensure that Plazomicin exposures lie within an acceptable range of the target mean steady-state area the curve (AUC).

Phase 1

• Conditions: Bloodstream infections (BSI) and nosocomial pneumonia due to carbapenem-resistant Enterobacteriaceae (CRE); MedDRA version: 18.0Level: LLTClassification code 10018657Term: Gram-negative bacterial infection NOSSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2013-001997-18-FR
• Lead Sponsor: Achaogen, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-09-29
• Study Completion: 2016-09-15
• Last Update Posted: 13 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 69

Inclusion Criteria

•Male and female patients age 18 to 85 years, inclusive
•APACHE II score between 15 and 30, inclusive
•Presumptive identification of a carbapenem resistant-member of the Enterobacteriaceae as defined by rapid testing methods from an appropriate culture specimen = 72 hours prior to study OR definitive identification of a carbapenem resistant-member of the Enterobacteriaceae as defined by local lab identification and susceptibility testing from an appropriate culture specimen = 72 hours prior to study entry
•Diagnosis of BSI as defined by at least one positive blood culture meeting the above microbiological criteria associated with at least one of the following signs of infection: Fever or hypothermia; New onset arterial hypotension; Elevated total peripheral white blood cell (WBC) count > 10,000 cells/mm3, > 15% immature neutrophils (band forms) regardless of total peripheral WBC count, or leukopenia with total WBC count < 4500 cells/mm3
•Or, diagnosis of nosocomial pneumonia in a patient on mechanical ventilation, as defined by lower respiratory tract or pleural fluid culture meeting the above defined microbiological criteria, and associated with the following clinical signs of pneumonia: A chest X-ray or computed tomography (CT) scan with findings consistent with a diagnosis of pneumonia; Worsening gas exchange; Purulent deep respiratory specimen; AND one of the following: Elevated total peripheral WBC count > 10,000 cells/mm3, > 15% immature neutrophils (band forms) regardless of total peripheral WBC count, or leukopenia with total WBC count < 4500 cells/mm3; Fever or hypothermia

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 179
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 179

Exclusion Criteria

•Patient has received more than 72 hours of empirical therapy
•Infection with CRE isolate with reduced susceptibilty to colistin
•Presence of refractory septic shock
•Objective clinical evidence for any of the following clinical syndromes that necessitates antimicrobial therapy for greater than 14 days: endovascular infection including endocarditis, osteomyelitis, prosthetic joint infection, meningitis and/or other central nervous system infections
•Objective clinical evidence of infectious involvement of intravascular material not intended to be removed within 4 calendar days of initial positive culture
•Pulmonary disease that precludes evaluation of therapeutic response including known bronchial obstruction or a history of post-obstructive pneumonia, tracheobronchitis, primary lung cancer or malignancies metastatic to the lung, bronchiectasis, known or suspected active tuberculosis
•Patients with severe liver disease (Child-Pugh score of Class C)
•Patients in acute renal failure or on intermittent hemodialysis (IHD) at the time of screening
•Patients with a history of seizure disorder and who are receiving anti-convulsive therapy
•Diagnosis of myasthenia gravis or any other neuromuscular disorder

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified