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).
- Conditions
- Bloodstream infections (BSI) and nosocomial pneumonia due to carbapenem-resistant Enterobacteriaceae (CRE)MedDRA version: 14.1Level: LLTClassification code 10018657Term: Gram-negative bacterial infection NOSSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2013-001997-18-IT
- Lead Sponsor
- Achaogen, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 358
•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
•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
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to demonstrate the superiority, in terms of all-cause mortality at 28 days, of a plazomicin-based regimen compared with a colistin-based regimen in the treatment of BSI or nosocomial pneumonia due to CRE.;Secondary Objective: The secondary objectives of this study are:<br>- to compare additional efficacy outcomes and safety of a plazomicin-based regimen with a colistin-based regimen in the treatment of BSI or nosocomial pneumonia due to CRE <br>- to evaluate the PK of intravenous (IV) plazomicin in patients with CRE infection.<br>- to evaluate the clinical utility of TDM for plazomicin dose adjustment;Primary end point(s): The primary efficacy endpoint is all-cause mortality;Timepoint(s) of evaluation of this end point: 28 days
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Secondary efficacy parameters include time to death through Day 28; all-cause mortality at 14 days after randomization; assessment of clinical response (as determined by the adjudication committee) at end of treatment, test of cure, and end of study; overall incidence of adverse events; plazomicin PK parameters; and frequency with which the use of TDM leads to a dose adjustment of plazomicin.;Timepoint(s) of evaluation of this end point: 14 and 28 days