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

June 4, 2017 updated by: Cardeas Pharma

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)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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. The study was designed to enroll up to 150 patients with the desire to enroll at least 140 patients with gram negative pneumonia. The study was terminated at 143 when that goal was achieved

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
143

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Tours, France, 37044
    • Limousin
      • Limoges, Limousin, France, 87042
    • Loiret
      • Orléans, Loiret, France, 45000
    • Meurthe-et-Moselle
      • Vandoeuvre les Nancy, Meurthe-et-Moselle, France, 54500
    • Île-de-France
      • Colombes, Île-de-France, France, 92701
  • Greece
      • Athens, Greece, 11527
      • Athens, Greece, 12462
      • Athens, Greece, 10676
      • Athens, Greece, 15227
      • Ioannina, Greece, 45500
      • Larisa, Greece, 41334
    • Evros
      • Alexandroupoli, Evros, Greece, 68100
  • Hungary
      • Budapest, Hungary, 1125
      • Budapest, Hungary, 1081
    • Hajdú-Bihar
      • Debrecen, Hajdú-Bihar, Hungary, 4012
      • Debrecen, Hajdú-Bihar, Hungary, 4043
  • Puerto Rico
      • San Juan, Puerto Rico, 00921
  • Spain
      • Barcelona, Spain, 08036
    • Baleares
      • Palma de Majorca, Baleares, Spain, 07010
    • Comunidad de Madrid
      • Getafe, Comunidad de Madrid, Spain, 28905
  • Turkey
      • Ankara, Turkey, 06110
      • Istanbul, Turkey, 34760
      • Istanbul, Turkey, 34098
      • Trabzon, Turkey, 61080
    • Ankara
      • Anakara, Ankara, Turkey, 06100
  • United States
    • California
      • Los Angeles, California, United States, 90033
    • Florida
      • Gainesville, Florida, United States, 32610
      • Jacksonville, Florida, United States, 32209
    • Illinois
      • Chicago, Illinois, United States, 60612
    • Kentucky
      • Hazard, Kentucky, United States, 41701
      • Lexington, Kentucky, United States, 21686
    • Massachusetts
      • Boston, Massachusetts, United States, 02119
      • Burlington, Massachusetts, United States, 01805
      • Springfield, Massachusetts, United States, 01199
    • Michigan
      • Detroit, Michigan, United States, 48202
    • Missouri
      • Saint Louis, Missouri, United States, 63110
    • Nebraska
      • Omaha, Nebraska, United States, 60198
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
    • Texas
      • El Paso, Texas, United States, 79905
      • Houston, Texas, United States, 77030

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Amikacin fosfomycin inhalation solution
300 mg of amikacin and 120 mg of fosfomycin twice daily for 10 days to be administered by aerosol via the eFlow Inline System.
Drug: Amikacin fosfomycin inhalation solution
300 mg of amikacin and 120 mg of fosfomycin twice daily for 10 days to be administered by aerosol via the eFlow Inline System
Other Names:
  • eFlow Inline System
  • Amikacin fosfomycin inhalation system (AFIS)
PLACEBO_COMPARATOR: Aerosolized placebo
Aerosolized placebo twice daily for 10 days administered using the eFlow Inline System
Drug: Aerosolized placebo
Placebo twice daily for 10 days to be administered by aerosol the eFlow Inline System
Other Names:
  • eFlow Inline System

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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 .
Time Frame: 10 day treatment period.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Composite Endpoint of Mortality and Clinical Cure
Time Frame: Day 1 - Day 28
The hierarchical composite endpoint of mortality, then clinical cure (defined as both absence of Gram-negative bacteria and CPIS at Day 14 < 6). The tables reflect a winner of matched pairs, ties are not noted.
Day 1 - Day 28
Composite Endpoint of Mortality and Ventilator-free Days
Time Frame: Day 1- Day 28
The hierarchical composite endpoint of mortality, then ventilator-free days. The table reflects winners of matched pairs, ties are not noted.
Day 1- Day 28
Number of Days Free of Mechanical Ventilation From Day 1 Through Day 28
Time Frame: Day 1 - Day 28
Number of days free of mechanical ventilation from Day 1 through Day 28 mean days.
Day 1 - Day 28
Number of ICU Days From Day 1 Through Day 28
Time Frame: Day 1 - Day 28
Day 1 - Day 28
Microbiological Response Rates in Patients Positive for Multi-drug Resistant Gram-negative Bacteria
Time Frame: Day 14
Microbiological response rates at Day 14 in patients whose pre-study treatment bronchoalveolar lavage (BAL) was positive for multi-drug resistant Gram-negative bacteria. Response is defined as not have a positive tracheal aspirate culture on Day 14
Day 14
Mortality From Day 1 Through Day 28
Time Frame: Day 1 - Day 28
Mortality from Day 1 through Day 28, all causes, does not reflect just infection only
Day 1 - Day 28
Clinical Relapse Rate
Time Frame: Day 11 - Day 28
Clinical relapse rates (defined as a new episode of pneumonia requiring reinstitution of IV antibiotics) from Day 11 through Day 28
Day 11 - Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cardeas Pharma

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marin Kollef, M.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2013

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2016

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 22, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 22, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 25, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 2, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 4, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CAP-01-102
  • 2013-002855-13 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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