Aerosolized Amikacin and Fosfomycin in Mechanically Ventilated Patients With Gram-negative Pneumonia
Information source: Cardeas Pharma
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pneumonia, Bacterial
Intervention: Amikacin fosfomycin inhalation solution (Drug); Aerosolized placebo (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Cardeas Pharma Official(s) and/or principal investigator(s): Marin Kollef, M.D., Principal Investigator, Affiliation: Washington University School of Medicine
Overall contact: Cardeas Clinical Trials, Phone: 206 973 1026, Email: info@cardeaspharma.com
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.
Clinical Details
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)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Change from baseline in Clinical Pulmonary Infection Score (CPIS) during the planned 10-day treatment period.
Secondary outcome: Composite endpoint of mortality and clinical cureComposite endpoint of mortality and ventilator-free days Number of days free of mechanical ventilation from Day 1 through Day 28 Number of ICU days from Day 1 through Day 28 Microbiological response rates in patients positive for multi-drug resistant Gram-negative bacteria Mortality from Day 1 through Day 28 Clinical relapse rate
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
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
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
Locations and Contacts
Cardeas Clinical Trials, Phone: 206 973 1026, Email: info@cardeaspharma.com
Tours 37044, France; Recruiting
Vesoul 70000, France; Withdrawn
Athens 15227, Greece; Recruiting
Athens 11527, Greece; Recruiting
Athens 12462, Greece; Recruiting
Athens 10676, Greece; Recruiting
Ioannina 45500, Greece; Recruiting
Larisa 41334, Greece; Recruiting
Budapest 1081, Hungary; Recruiting
Budapest 1106, Hungary; Recruiting
Budapest 1115, Hungary; Recruiting
Budapest 1125, Hungary; Recruiting
Kistarcsa 2143, Hungary; Recruiting
Pécs 7623, Hungary; Recruiting
Törökbálint 2045, Hungary; Recruiting
San Juan 00921, Puerto Rico; Recruiting
Barcelona 08003, Spain; Recruiting
Barcelona 08036, Spain; Recruiting
Ankara 06110, Turkey; Recruiting
Istanbul 34098, Turkey; Recruiting
Istanbul 34760, Turkey; Recruiting
Trabzon 61080, Turkey; Recruiting
Anakara, Ankara 06100, Turkey; Recruiting
Palma de Mallorca, Baleares 07010, Spain; Recruiting
Gyula, Békés 5700, Hungary; Recruiting
Los Angeles, California 90033, United States; Not yet recruiting
Getafe, Comunidad de Madrid 28905, Spain; Recruiting
Alexandroupolis, Evros 68100, Greece; Recruiting
Gainesville, Florida 32610, United States; Recruiting
Jacksonville, Florida 32209, United States; Recruiting
Debrecen, Hajdú-Bihar 4043, Hungary; Recruiting
Debrecen, Hajdú-Bihar 4012, Hungary; Recruiting
Chicago, Illinois 60612, United States; Recruiting
Hazard, Kentucky 41701, United States; Recruiting
Lexington, Kentucky 21686, United States; Recruiting
Limoges, Limousin 87042, France; Recruiting
Orléans, Loiret 45000, France; Recruiting
Boston, Massachusetts 02115, United States; Recruiting
Boston, Massachusetts 02119, United States; Recruiting
Burlington, Massachusetts 01805, United States; Recruiting
Springfield, Massachusetts 01199, United States; Recruiting
Vandoeuvre les Nancy, Meurthe-et-Moselle 54500, France; Recruiting
Detroit, Michigan 48202, United States; Recruiting
Kalamazoo, Michigan 49048, United States; Recruiting
St. Louis, Missouri 63110, United States; Recruiting
Omaha, Nebraska 60198, United States; Recruiting
Newark, New Jersey 07102, United States; Recruiting
Valhalla, New York 10595, United States; Recruiting
Oklahoma City, Oklahoma 73104, United States; Recruiting
Pittsburgh, Pennsylvania 15213, United States; Recruiting
Knoxville, Tennessee 37920, United States; Recruiting
El Paso, Texas 79905, United States; Recruiting
Houston, Texas 77030, United States; Recruiting
Colombes, ÃŽle-de-France 92701, France; Recruiting
Additional Information
MedlinePlus related topics: Antibiotics MedlinePlus related topics: Pneumonia Drug Information available for amikacin Drug information available for fosfomycin U.S. FDA Resources
Starting date: December 2013
Last updated: July 27, 2015
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