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

• Status: Completed
• Trial end date: 2016-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cardeas Pharma
• Treatments: Amikacin; Fosfomycin

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 the most recent chest radiograph 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 ≤ 350 mmHg

• Acute Physiology and Chronic Health Evaluation (APACHE) II score > 10 (within 24 hours prior to screening)

• 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 72 hours at the time of randomization

• 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)

• 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 > 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)

• Positive urine and/or serum beta-hCG pregnancy test (only in women of reproductive age)

• On mechanical ventilation for > 28 days

• 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