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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Department of Health and Human Services
Information provided by (Responsible Party):
Achaogen, Inc.
ClinicalTrials.gov Identifier:
NCT01970371
First received: October 23, 2013
Last updated: September 1, 2016
Last verified: September 2016
  Purpose
This is a Phase 3 study containing a randomized open-label superiority cohort (Cohort 1) 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. An additional cohort of patients with BSI, HABP, VABP, cUTI, or AP due to CRE, not eligible for inclusion in the other cohort, will be enrolled into a single arm (Cohort 2) and treated with plazomicin-based therapy. 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
Complicated Urinary Tract Infection (cUTI) Due to CRE
Acute Pyelonephritis (AP) Due to CRE
Drug: plazomicin
Drug: colistin
Drug: meropenem
Drug: tigecycline
Drug: antibiotic of Investigator's choice
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 in Cohort 1 [ 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) in Cohort 1 [ Time Frame: 14-21 days ] [ Designated as safety issue: No ]
  • All-cause mortality at Day 28 in Cohort 1 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Time to death through Day 28 in Cohort 1 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • All-cause mortality at Day 14 in Cohort 1 [ 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 ]

Enrollment: 69
Study Start Date: September 2014
Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Plazomicin in Combination with Meropenem or Tigecycline
Cohort 1
Drug: plazomicin
intravenous repeating doses
Drug: meropenem
intravenous repeating doses
Drug: tigecycline
intravenous repeating doses
Active Comparator: Colistin in Combination with Meropenem or Tigecycline
Cohort 1
Drug: colistin
intravenous repeating doses
Other Name: colistimethate sodium
Drug: meropenem
intravenous repeating doses
Drug: tigecycline
intravenous repeating doses
Experimental: Plazomicin in Combination with Adjunctive Antibiotic
Cohort 2
Drug: plazomicin
intravenous repeating doses
Drug: antibiotic of Investigator's choice
repeating doses

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Principal Inclusion Criteria:

  • Cohort 1: APACHE II score between 15 and 30, inclusive; Cohort 2: BSI, HABP, VABP patients with an APACHE II score ≤30 (cUTI and AP patients do not need to have their APACHE II score calculated)
  • Positive culture that was collected ≤96 hours prior to randomization indicating a CRE infection, or a high likelihood of 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, increased 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
  • Or, diagnosis of cUTI or AP defined by clinical signs and symptoms consistent with cUTI or AP assessed within 24 hours prior to enrollment

Principal Exclusion Criteria:

  • Cohorts 1 and 2 BSI, HABP, and VABP patients: receipt of more than 72 hours of potentially effective antibacterial therapy; Cohort 2: cUTI and AP patients: receipt of any potentially effective antibacterial therapy in the 48 hours prior to enrollment
  • Cohort 1 only: 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
  • HABP or VABP patients only: 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
  • cUTI or AP patients only: renal abscess, chronic bacterial prostatitis, orchitis or epididymitis, polycystic kidney disease, one functional kidney, vesicoureteral reflux, renal transplant, cystectomy or ileal loop surgery, fungal UTI or complete, permanent obstruction of the urinary tract
  • Patients in acute renal failure at the time of randomization
  • Patients receiving intermittent hemodialysis (IHD) at the time of screening
  • Pregnant or breastfeeding female patient
  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

  Show 31 Study Locations
Sponsors and Collaborators
Achaogen, Inc.
Department of Health and Human Services
Investigators
Study Director: Lynn E Connolly, MD, PhD Achaogen, Inc.
  More Information

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: September 1, 2016
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
Argentina: Ministry of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Achaogen, Inc.:
Gram-negative
bacterial infection
antibacterial
antimicrobial
CRE
CPE
BSI
pneumonia
HABP
VABP
AP
cUTI
UTI

Additional relevant MeSH terms:
Infection
Communicable Diseases
Pneumonia
Urinary Tract Infections
Pyelonephritis
Pneumonia, Bacterial
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Urologic Diseases
Nephritis, Interstitial
Nephritis
Kidney Diseases
Pyelitis
Bacterial Infections
Anti-Bacterial Agents
Meropenem
Colistin
Tigecycline
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents

ClinicalTrials.gov processed this record on September 23, 2016