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: 16.1Level: LLTClassification code 10018657Term: Gram-negative bacterial infection NOSSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2013-001997-18-ES
- 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