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

NCT02218359 | Withdrawn Phase 2

• 1 other identifier: CAP-01-103
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Pneumonia, Bacterial

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change from baseline in tracheal aspirate Gram-negative and Gram-positive bacterial density

  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

  5 day randomized course of study drug

Secondary Outcomes (5)

• Microbiological response rate in patients with multidrug resistant Gram-negative bacteria

  Day 5

• Eradication of bacteria

  Days 10, 21, and 28

• Clinical worsening

  Day 1 - Day 28

• Microbiological response rates

  Day 10

• Microbiological response rates in patients with MRSA

  Day 5

Study Arms (2)

Amikacin Fosfomycin Inhalation Solution

EXPERIMENTAL

300 mg of amikacin and 120 mg of fosfomycin to be administered by aerosol via the AFIS Inline System.

Drug: Amikacin Fosfomycin Inhalation Solution

Aerosolized Placebo

PLACEBO COMPARATOR

Aerosolized placebo to be administered by aerosol using the AFIS Inline System.

Drug: Aerosolized placebo; Drug: Amikacin Fosfomycin Inhalation Solution

Interventions

Amikacin Fosfomycin Inhalation Solution DRUG

300 mg of amikacin and 120 mg of fosfomycin twice daily for 10 days to be administered by aerosol via the AFIS Inline System

Also known as: Amikacin Fosfomycin Inhalation System (AFIS), eFlow Inline System

Amikacin Fosfomycin Inhalation Solution

Aerosolized placebo DRUG

Placebo twice daily for Days 1 -5 to be administered by aerosol using the eFlow Inline System.

Also known as: eFlow Inline System

Aerosolized Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cardeas Pharma: lead

Related Links

• MedlinePlus related topics: Antibiotics
• MedlinePlus related topics: Pneumonia
• Drug Information available for amikacin
• Drug information available for fosfomycin
• U.S. FDA Resources

MeSH Terms

Conditions

Pneumonia, Bacterial; Pneumonia; Bacterial Infections; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Study Officials

• Bruce Montgomery, M.D.

  Cardeas Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2014
• First Posted: August 18, 2014
• Study Start: October 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2016
• Last Updated: November 18, 2015

Record last verified: 2015-11