Aerosolized Amikacin and Fosfomycin in Mechanically Ventilated Patients With Gram-negative Pneumonia (IASIS)

This study is currently recruiting participants.
Verified February 2014 by Cardeas Pharma
Sponsor:
Information provided by (Responsible Party):
Cardeas Pharma
ClinicalTrials.gov Identifier:
NCT01969799
First received: October 22, 2013
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

To demonstrate the safety and efficacy of adjunctive therapy with the Amikacin fosfomycin inhalation system (AFIS) versus aerosolized placebo to treat Gram-negative pneumonia in mechanically ventilated patients receiving IV antibiotics.


Condition Intervention Phase
Pneumonia, Bacterial
Drug: Amikacin fosfomycin inhalation solution
Drug: Aerosolized placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Blinded, Placebo-Controlled, Phase 2 Study of Aerosolized Amikacin and Fosfomycin Delivered Via the Investigational eFlow® Inline System in Mechanically Ventilated Patients With Gram-negative Bacterial Pneumonia (IASIS)

Resource links provided by NLM:


Further study details as provided by Cardeas Pharma:

Primary Outcome Measures:
  • Change from baseline in Clinical Pulmonary Infection Score (CPIS) during the planned 10-day treatment period. [ Time Frame: 10 day treatment period. ] [ Designated as safety issue: No ]
    Daily CPIS will be determined by one blinded, central reviewer in order to minimize inter-observer variability.


Secondary Outcome Measures:
  • Composite endpoint of mortality and ventilator-free days [ Time Frame: Day 1- Day 28 ] [ Designated as safety issue: No ]
    The hierarchical composite endpoint of mortality and ventilator-free days.

  • Number of days free of mechanical ventilation from Day 1 through Day 28 [ Time Frame: Day 1 - Day 28 ] [ Designated as safety issue: No ]
  • Number of ICU days from Day 1 through Day 28 [ Time Frame: Day 1 - Day 28 ] [ Designated as safety issue: No ]
  • Microbiological response rates in patients positive for multi-drug resistant Gram-negative bacteria [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    Microbiological response rates at Day 14 in patients whose pre-study treatment bronchoalveolar lavage (BAL) was positive for multi-drug resistant Gram-negative bacteria

  • Mortality from Day 1 through Day 28 [ Time Frame: Day 1 - Day 28 ] [ Designated as safety issue: No ]
  • Clinical relapse rate [ Time Frame: Day 11 - Day 28 ] [ Designated as safety issue: No ]
    Clinical relapse rates (defined as a new episode of pneumonia requiring reinstitution of IV antibiotics) from Day 11 through Day 28


Estimated Enrollment: 150
Study Start Date: December 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amikacin fosfomycin inhalation solution
300 mg of amikacin and 120 mg of fosfomycin twice daily for 10 days to be administered by aerosol via the eFlow Inline System.
Drug: Amikacin fosfomycin inhalation solution
300 mg of amikacin and 120 mg of fosfomycin twice daily for 10 days to be administered by aerosol via the eFlow Inline System
Other Names:
  • Amikacin fosfomycin inhalation system (AFIS)
  • eFlow Inline System
Placebo Comparator: Aerosolized placebo
Aerosolized placebo twice daily for 10 days administered using the eFlow Inline System
Drug: Aerosolized placebo
Placebo twice daily for 10 days to be administered by aerosol the eFlow Inline System
Other Names:
  • Aerosolized placebo
  • eFlow Inline System

Detailed Description:

The primary purpose of this study is to demonstrate the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS). AFIS consists of amikacin solution and fosfomycin solution, delivered by aerosol to the lungs via the PARI Investigational eFlow Inline System (eFlow Inline System). All patients will receive a standardized course of intravenous (IV) antibiotics for a minimum of 7 days. Patients will be randomized to receive 10 days of treatment with either AFIS or placebo, in addition to the IV therapy. The primary efficacy endpoint is defined as the change from baseline in the Clinical Pulmonary Infection Score (CPIS) during the randomized course of study drug.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and non-pregnant, non-lactating females, ≥ 18 years and ≤ 80 years of age
  • Intubated and mechanically ventilated
  • Diagnosis of pneumonia, defined as presence of a new or progressive infiltrate(s) on chest radiograph (within 24 hours prior to screening), as determined by the treating physician
  • Signs of infection (within 24 hours prior to screening):

    1. Fever (> 38ºC or > 100.4ºF); or
    2. Leukopenia (< 4,000 WBC/mm3) or leukocytosis (≥ 12,000 WBC/mm3)
  • Impaired oxygenation (within 24 hours prior to screening):

    a. PaO2/FiO2 ≤ 300 mmHg

  • Acute Physiology and Chronic Health Evaluation (APACHE) II score > 10 on the day of ICU admission
  • Presence, or high suspicion, of Gram-negative organism(s) by either Gram stain or culture of respiratory secretions from a sample obtained within the previous 7 days (enrollment can occur before culture results are available)

Exclusion Criteria:

  • History of hypersensitivity to amikacin, other aminoglycosides, fosfomycin, imipenem, meropenem, or colistin
  • Received systemic antibiotic therapy for this episode of Gram-negative pneumonia for greater than 48 hours at the time of randomization
  • PaO2/FiO2 ≤ 100 mmHg plus diffuse infiltrates on Chest X-ray
  • Septic shock (defined as severe sepsis plus refractory [> 6 hours duration] hypotension)
  • Any of the following conditions that interfere with the assessment or interpretation of the diagnosis or response to therapy:

    1. chest trauma with ongoing loss of stability of the thoracic cage following a fracture of the sternum, ribs, or both;
    2. increased amounts of fluid in the lung cavities requiring chest tube drainage;
    3. lung cancer within the last 2 years;
    4. lung abscess(s);
    5. anatomical bronchial obstruction;
    6. suspected atypical pneumonia;
    7. chemical pneumonitis (e.g., inhalation injury);
    8. cystic fibrosis
  • Immunocompromised patients, including those with neutropenia NOT due to the current infection (absolute neutrophil count < 500/mm3), leukemia, lymphoma, human immunodeficiency virus (HIV) infection with CD4 count < 200 cells/mm3, or splenectomy; those who are early post-transplantation (< 3 months post-transplant, or > 3 months post-transplant with evidence of organ rejection by clinical criteria, pathologic confirmation, or modification of immunosuppression within the past 4 weeks), are on cytotoxic chemotherapy, or are on high-dose steroids (e.g., > 40 mg of prednisone or its equivalent [> 160 mg hydrocortisone, > 32 mg methylprednisolone, > 6 mg dexamethasone, > 200 mg cortisone] daily for > 2 weeks)
  • Evidence of significant renal impairment (serum creatinine > 2.0 mg/dL within 24 hours prior to screening)
  • Evidence of ototoxicity (history of hearing aid use prior to current hospitalization)
  • Evidence of hepatotoxicity (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >3X the upper limit of normal value within 24 hours prior to screening)
  • Positive urine and/or serum beta-hCG pregnancy test (only in women of reproductive age)
  • On mechanical ventilation for > 28 days
  • Head injury or stroke that will likely require continued mechanical ventilation after resolution of pneumonia, or Glasgow Coma Scale score ≤ 3 at Screening
  • Participating in or has participated in other investigational interventional studies (drug or device) within the last 30 days (or 5 times the half-life of the previously administered investigational compound, whichever is longer) prior to study treatment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01969799

Contacts
Contact: Cardeas Clinical Trials 206 973 1026 info@cardeaspharma.com

  Show 54 Study Locations
Sponsors and Collaborators
Cardeas Pharma
Investigators
Principal Investigator: Marin Kollef, M.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Cardeas Pharma
ClinicalTrials.gov Identifier: NCT01969799     History of Changes
Other Study ID Numbers: CAP-01-102, 2013-002855-13
Study First Received: October 22, 2013
Last Updated: February 27, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Cardeas Pharma:
Pneumonia, Bacterial
Gram-negative pneumonia
Aerosol antibiotics
Mechanical ventilation
Amikacin
Fosfomycin
Pneumonia
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

Additional relevant MeSH terms:
Pneumonia, Bacterial
Pneumonia
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Amikacin
Fosfomycin
Anti-Infective Agents
Anti-Bacterial Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 14, 2014