Aerosolized Amikacin and Fosfomycin in Mechanically Ventilated Patients With Gram-negative Pneumonia
IASIS
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)
2 other identifiers
interventional
143
7 countries
41
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Dec 2013
41 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 22, 2013
CompletedFirst Posted
Study publicly available on registry
October 25, 2013
CompletedStudy Start
First participant enrolled
December 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2016
CompletedResults Posted
Study results publicly available
July 2, 2017
CompletedJuly 2, 2017
March 1, 2016
2.2 years
October 22, 2013
July 8, 2016
June 4, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline in Clinical Pulmonary Infection Score (CPIS) For Each Patient, Value Obtained From a Daily Assessment Over the 10 Day Study Period Was Compared to Baseline, and the LSM Data Represent the Change From Baseline Data Over All Days .
Change from baseline in Clinical Pulmonary Infection Score (CPIS) For each patient, value obtained from a daily assessment over the 10 day study period was compared to baseline, and the LSM data represent the change from baseline data over all days. Daily CPIS will be determined by one blinded, central reviewer in order to minimize inter-observer variability. The scale ranges from 0 to 13, with 13 being the worst. The value of zero would be a healthy patient with no evidence of pneumonia. For each patient, there was a daily assessment for the 10 day study period.
10 day treatment period.
Secondary Outcomes (7)
Composite Endpoint of Mortality and Clinical Cure
Day 1 - Day 28
Composite Endpoint of Mortality and Ventilator-free Days
Day 1- Day 28
Number of Days Free of Mechanical Ventilation From Day 1 Through Day 28
Day 1 - Day 28
Number of ICU Days From Day 1 Through Day 28
Day 1 - Day 28
Microbiological Response Rates in Patients Positive for Multi-drug Resistant Gram-negative Bacteria
Day 14
- +2 more secondary outcomes
Study Arms (2)
Amikacin fosfomycin inhalation solution
EXPERIMENTAL300 mg of amikacin and 120 mg of fosfomycin twice daily for 10 days to be administered by aerosol via the eFlow Inline System.
Aerosolized placebo
PLACEBO COMPARATORAerosolized placebo twice daily for 10 days administered using the eFlow Inline System
Interventions
300 mg of amikacin and 120 mg of fosfomycin twice daily for 10 days to be administered by aerosol via the eFlow Inline System
Placebo twice daily for 10 days to be administered by aerosol the eFlow Inline System
Eligibility Criteria
You may qualify if:
- 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):
- Fever (\> 38ºC or \> 100.4ºF); or
- 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)
You may not qualify if:
- 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:
- chest trauma with ongoing 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
- 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
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Cardeas Pharmalead
Study Sites (41)
Unknown Facility
Los Angeles, California, 90033, United States
Unknown Facility
Gainesville, Florida, 32610, United States
Unknown Facility
Jacksonville, Florida, 32209, United States
Unknown Facility
Chicago, Illinois, 60612, United States
Unknown Facility
Hazard, Kentucky, 41701, United States
Unknown Facility
Lexington, Kentucky, 21686, United States
Unknown Facility
Boston, Massachusetts, 02119, United States
Unknown Facility
Burlington, Massachusetts, 01805, United States
Unknown Facility
Springfield, Massachusetts, 01199, United States
Unknown Facility
Detroit, Michigan, 48202, United States
Unknown Facility
St Louis, Missouri, 63110, United States
Unknown Facility
Omaha, Nebraska, 60198, United States
Unknown Facility
Oklahoma City, Oklahoma, 73104, United States
Unknown Facility
Knoxville, Tennessee, 37920, United States
Unknown Facility
El Paso, Texas, 79905, United States
Unknown Facility
Houston, Texas, 77030, United States
Unknown Facility
Limoges, Limousin, 87042, France
Unknown Facility
Orléans, Loiret, 45000, France
Unknown Facility
Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54500, France
Unknown Facility
Tours, 37044, France
Unknown Facility
Colombes, Île-de-France Region, 92701, France
Unknown Facility
Alexandroupoli, Evros, 68100, Greece
Unknown Facility
Athens, 10676, Greece
Unknown Facility
Athens, 11527, Greece
Unknown Facility
Athens, 12462, Greece
Unknown Facility
Athens, 15227, Greece
Unknown Facility
Ioannina, 45500, Greece
Unknown Facility
Larissa, 41334, Greece
Unknown Facility
Debrecen, Hajdú-Bihar, 4012, Hungary
Unknown Facility
Debrecen, Hajdú-Bihar, 4043, Hungary
Unknown Facility
Budapest, 1081, Hungary
Unknown Facility
Budapest, 1125, Hungary
Unknown Facility
San Juan, 00921, Puerto Rico
Unknown Facility
Palma de Majorca, Balearic Islands, 07010, Spain
Unknown Facility
Getafe, Madrid, 28905, Spain
Unknown Facility
Barcelona, 08036, Spain
Unknown Facility
Ankara, Ankara, 06100, Turkey (Türkiye)
Unknown Facility
Ankara, 06110, Turkey (Türkiye)
Unknown Facility
Istanbul, 34098, Turkey (Türkiye)
Unknown Facility
Istanbul, 34760, Turkey (Türkiye)
Unknown Facility
Trabzon, 61080, Turkey (Türkiye)
Related Publications (1)
Kollef MH, Ricard JD, Roux D, Francois B, Ischaki E, Rozgonyi Z, Boulain T, Ivanyi Z, Janos G, Garot D, Koura F, Zakynthinos E, Dimopoulos G, Torres A, Danker W, Montgomery AB. A Randomized Trial of the Amikacin Fosfomycin Inhalation System for the Adjunctive Therapy of Gram-Negative Ventilator-Associated Pneumonia: IASIS Trial. Chest. 2017 Jun;151(6):1239-1246. doi: 10.1016/j.chest.2016.11.026. Epub 2016 Nov 24.
PMID: 27890714DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bruce Montgomery, MD
- Organization
- Cardeas Pharma
Study Officials
- PRINCIPAL INVESTIGATOR
Marin Kollef, M.D.
Washington University School of Medicine
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 22, 2013
First Posted
October 25, 2013
Study Start
December 1, 2013
Primary Completion
March 1, 2016
Study Completion
April 1, 2016
Last Updated
July 2, 2017
Results First Posted
July 2, 2017
Record last verified: 2016-03