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Aerosolized Amikacin and Fosfomycin in Mechanically Ventilated Patients With Gram-negative and / or Gram-positive Bacterial Colonization

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02218359
Recruitment Status : Withdrawn (No Participants Enrolled)
First Posted : August 18, 2014
Last Update Posted : November 18, 2015
Sponsor:
Information provided by (Responsible Party):
Cardeas Pharma

Brief Summary:
To demonstrate the safety and efficacy of adjunctive therapy with the Amikacin Fosfomycin Inhalation System (AFIS) versus aerosolized placebo in mechanically ventilated patients with Gram-negative and / or Gram-positive bacterial colonization.

Condition or disease Intervention/treatment Phase
Pneumonia, Bacterial Drug: Amikacin Fosfomycin Inhalation Solution Drug: Aerosolized placebo Phase 2

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 (AMS) and fosfomycin solution (FFS), delivered by aerosol to the lungs via the Investigational eFlow AFIS Inline System (AFIS Inline System) with tamper evident reservoir. Patients will be randomized to receive 5 days of treatment with either AFIS or placebo, followed by all patients receiving open label AFIS for five days. The primary efficacy endpoint is the change from baseline in tracheal aspirate Gram-negative and/or Gram-positive bacterial density at the end of the 5-day randomized course of study drug.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blind, Placebo-Controlled, Crossover to Open Label, Phase 2 Study of Aerosolized Amikacin and Fosfomycin Delivered Via the Investigational eFlow® AFIS Inline System in Mechanically Ventilated Patients With Gram-negative and/or Gram-positive Bacterial Colonization
Study Start Date : October 2014
Estimated Primary Completion Date : December 2015
Estimated Study Completion Date : January 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Amikacin Fosfomycin Inhalation Solution
300 mg of amikacin and 120 mg of fosfomycin to be administered by aerosol via the AFIS 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 AFIS Inline System
Other Names:
  • Amikacin Fosfomycin Inhalation System (AFIS)
  • eFlow Inline System

Drug: Amikacin Fosfomycin Inhalation Solution
Open-label crossover for all patients Days 6-10
Other Names:
  • Amikacin Fosfomycin Inhalation System (AFIS)
  • eFlow Inline System

Placebo Comparator: Aerosolized Placebo
Aerosolized placebo to be administered by aerosol using the AFIS Inline System.
Drug: Aerosolized placebo
Placebo twice daily for Days 1 -5 to be administered by aerosol using the eFlow Inline System.
Other Name: eFlow Inline System

Drug: Amikacin Fosfomycin Inhalation Solution
Open-label crossover for all patients Days 6-10
Other Names:
  • Amikacin Fosfomycin Inhalation System (AFIS)
  • eFlow Inline System




Primary Outcome Measures :
  1. Change from baseline in tracheal aspirate Gram-negative and Gram-positive bacterial density [ Time Frame: 5 day randomized course of study drug ]
    Change from baseline in tracheal aspirate Gram-negative and Gram-positive bacterial density at the end of the 5-day randomized course of study drug


Secondary Outcome Measures :
  1. Microbiological response rate in patients with multidrug resistant Gram-negative bacteria [ Time Frame: Day 5 ]
    Microbiological response rates at Day 5 in patients whose pre-study treatment tracheal aspirate culture was positive for multidrug resistant (MDR) Gram-negative bacteria

  2. Eradication of bacteria [ Time Frame: Days 10, 21, and 28 ]
    Eradication of bacteria at Days 10, 21, and 28

  3. Clinical worsening [ Time Frame: Day 1 - Day 28 ]
    Clinical worsening (defined as requiring institution of IV antibiotics) from Day 1 through Day 28

  4. Microbiological response rates [ Time Frame: Day 10 ]
    Microbiological response rates at Day 10 in all patients

  5. Microbiological response rates in patients with MRSA [ Time Frame: Day 5 ]
    Microbiological response rates at Day 5 in patients whose pre-study treatment tracheal aspirate culture was positive for methicillin resistant Staphylococcus aureus (MRSA)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
  • Presence of Gram-negative and/or Gram-positive organism(s) by culture of respiratory secretions from a sample obtained within the previous 7 days

Exclusion Criteria:

  • History of hypersensitivity to amikacin or fosfomycin.
  • Diagnosis of pneumonia, defined as presence of a new or progressive infiltrate(s) on chest radiograph (within 7 days prior to screening), as determined by the treating physician
  • Use of systemic antibiotics with efficacy against likely respiratory tract pathogens at the time of randomization
  • Severe acute respiratory distress syndrome (defined as PaO2/FiO2 ≤ 100 mmHg and diffuse infiltrates on Chest X-ray)
  • Refractory septic shock (severe sepsis plus unstable hypotension, in spite of adequate fluid resuscitation and vasopressors)
  • Evidence of significant renal impairment (serum creatinine > 4.0 mg/dL within 24 hours prior to screening) . If serum creatinine is > 2.0 mg/dL, site must be capable of performing continuous renal replacement therapy, if clinically indicated. Patients with serum creatinine > 4.0 mg/dL and being treated with continuous renal replacement therapy (continuous venous-venous hemofiltration or continuous venous-venous hemodialysis) or chronic hemodialysis are eligible
  • 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)
  • Any of the following conditions that interfere with the assessment or interpretation of the diagnosis or response to therapy: chest trauma with loss of stability of the thoracic cage following a fracture of the sternum, ribs, or both; increased amounts of fluid in the lung cavities requiring chest tube drainage; lung cancer within the last 2 years; lung abscess(s); anatomical bronchial obstruction; suspected atypical pneumonia; chemical pneumonitis (e.g., inhalation injury); cystic fibrosis; congestive heart failure (leading to a PaO2/FiO2 ratio ≤ 100 mmHg and diffuse infiltrates on Chest X-ray)
  • 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, 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)
  • Positive urine and/or serum beta-hCG pregnancy test (only in women of reproductive age)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02218359


Sponsors and Collaborators
Cardeas Pharma
Investigators
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Study Director: Bruce Montgomery, M.D. Cardeas Pharma
Additional Information:
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Responsible Party: Cardeas Pharma
ClinicalTrials.gov Identifier: NCT02218359    
Other Study ID Numbers: CAP-01-103
First Posted: August 18, 2014    Key Record Dates
Last Update Posted: November 18, 2015
Last Verified: November 2015
Keywords provided by Cardeas Pharma:
Gram-negative pneumonia
Aerosol antibiotics
Mechanical ventilation
Amikacin
Fosfomycin
Pneumonia, Bacterial
Pneumonia
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
MRSA
Additional relevant MeSH terms:
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Pneumonia, Bacterial
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Bacterial Infections
Amikacin
Fosfomycin
Pharmaceutical Solutions
Anti-Bacterial Agents
Anti-Infective Agents