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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 cure

Composite 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, Île-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

Page last updated: August 23, 2015

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