A Study of Plazomicin Compared With Colistin in Patients With Infection Due to Carbapenem-Resistant Enterobacteriaceae (CRE)

This study is currently recruiting participants.
Verified March 2014 by Achaogen, Inc.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Achaogen, Inc.
ClinicalTrials.gov Identifier:
NCT01970371
First received: October 23, 2013
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

This is a Phase 3, randomized, open-label superiority study comparing the efficacy and safety of plazomicin with colistin when combined with a second antibiotic (either meropenem or tigecycline) in the treatment of patients with bloodstream infection (BSI) or nosocomial pneumonia due to CRE. Therapeutic drug management (TDM) will be used to help ensure that plazomicin exposures lie within an acceptable range of the target mean steady-state area under the curve (AUC).


Condition Intervention Phase
BSI Due to CRE
Nosocomial Pneumonia Due to CRE
Drug: plazomicin
Drug: colistin
Drug: meropenem
Drug: tigecycline
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Plazomicin Compared With Colistin in Patients With Infection Due to Carbapenem-Resistant Enterobacteriaceae (CRE)

Resource links provided by NLM:


Further study details as provided by Achaogen, Inc.:

Primary Outcome Measures:
  • All-cause mortality at 28 days [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to death through 28 days [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • All-cause mortality at 14 days [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Clinical response (as determined by the adjudication committee) at end of treatment [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Clinical response (as determined by the adjudication committee) at test of cure [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Clinical response (as determined by the adjudication committee) at end of study [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Overall incidence of adverse events [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • Plazomicin PK parameters including AUC0-24,Cmax, and Cmin [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Frequency with which the use of TDM leads to a dose adjustment of plazomicin [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Microbiological response at end of treatment [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Microbiological response at test of cure [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Microbiological response at end of study [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 360
Study Start Date: February 2014
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Plazomicin in Combination with Meropenem or Tigecycline
Intravenous repeating doses
Drug: plazomicin
Other Name: plazomicin sulfate
Drug: meropenem
Second adjunctive antibiotic therapy (Investigator's choice of either meropenem or tigecycline)
Drug: tigecycline
Second adjunctive antibiotic therapy (Investigator's choice of either meropenem or tigecycline)
Active Comparator: Colistin in Combination with Meropenem or Tigecycline
Intravenous repeating doses
Drug: colistin
Other Name: colistimethate sodium
Drug: meropenem
Second adjunctive antibiotic therapy (Investigator's choice of either meropenem or tigecycline)
Drug: tigecycline
Second adjunctive antibiotic therapy (Investigator's choice of either meropenem or tigecycline)

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Principal Inclusion Criteria:

  • 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

Principal Exclusion Criteria:

  • Patient has received more than 72 hours of empirical therapy
  • Infection with CRE isolate with reduced susceptibility 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01970371

Contacts
Contact: Clinical Trials Support clinical-trials@achaogen.com

Locations
United States, New Jersey
Investigational Site Recruiting
Englewood, New Jersey, United States
United States, Ohio
Investigational Site Recruiting
Cincinnati, Ohio, United States
United States, Pennsylvania
Investigational Site Recruiting
Pittsburgh, Pennsylvania, United States
United States, Texas
Investigational Site Recruiting
Houston, Texas, United States
Sponsors and Collaborators
Achaogen, Inc.
Investigators
Study Director: Lynn E Connolly, MD, PhD Achaogen, Inc.
  More Information

No publications provided

Responsible Party: Achaogen, Inc.
ClinicalTrials.gov Identifier: NCT01970371     History of Changes
Other Study ID Numbers: ACHN-490-007, 2013-001997-18, U1111-1151-2686
Study First Received: October 23, 2013
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Achaogen, Inc.:
Gram-negative
Bacterial infection

Additional relevant MeSH terms:
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Colistin
Meropenem
Tigecycline
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 21, 2014