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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Achaogen, Inc.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Achaogen, Inc.
ClinicalTrials.gov Identifier:
NCT01970371
First received: October 23, 2013
Last updated: August 6, 2015
Last verified: August 2015
  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), hospital acquired bacterial pneumonia (HABP), or ventilator-associated bacterial pneumonia (VABP) 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
Bloodstream Infections (BSI) Due to CRE
Hospital-Acquired Bacterial Pneumonia (HABP) Due to CRE
Ventilator-Associated Bacterial Pneumonia (VABP) 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 Day 28 or significant disease-related complications [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical failure (as determined by the adjudication committee) at test of cure (TOC) [ Time Frame: 14-21 days ] [ Designated as safety issue: No ]
  • All-cause mortality at Day 28 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Time to death through Day 28 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • All-cause mortality at Day 14 [ Time Frame: 14 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 ]

Estimated Enrollment: 360
Study Start Date: September 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
  • Positive blood (for BSI) or lower respiratory tract (for HABP/VABP) culture that was collected ≤ 96 hours prior to randomization indicating a CRE infection
  • Diagnosis of BSI as defined by at least one of the following: fever, hypothermia, new onset arterial hypotension, elevated total peripheral white blood cell (WBC) count, > 10% immature neutrophils (band forms), or leukopenia
  • Or, diagnosis of HABP defined as clinical signs and symptoms consistent with pneumonia acquired after at least 48 hours of continuous stay in an inpatient acute or chronic-care facility, or acquired within 7 days after being discharged from a hospitalization of ≥3 days duration
  • Or, diagnosis of VABP defined by clinical signs and symptoms consistent with pneumonia acquired after at least 48 hours of continuous mechanical ventilation.

Principal Exclusion Criteria:

  • Receipt of more than 72 hours of potentially effective antibacterial therapy
  • Knowledge that index CRE infection is resistant to colistin prior to randomization
  • Objective clinical evidence for any of the following clinical syndromes that necessitates study 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 potentially due to the study qualifying pathogen and not intended to be removed within 4 calendar days of the 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 in acute renal failure at the time of randomization
  • Patients receiving intermittent hemodialysis (IHD) at the time of screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01970371

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

  Show 35 Study Locations
Sponsors and Collaborators
Achaogen, Inc.
Investigators
Study Director: Adrian Jubb, MBChB 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: August 6, 2015
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Turkey: Drug and Medical Device Institution
Mexico: Federal Commission for Sanitary Risks Protection
Brazil: Brazilian Health Surveillance Agency (ANVISA)
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos

Keywords provided by Achaogen, Inc.:
Gram-negative
bacterial infection
antibacterial
antimicrobial

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

ClinicalTrials.gov processed this record on September 01, 2015