Inhaled Amikacin Solution BAY41-6551 as Adjunctive Therapy in the Treatment of Gram-Negative Pneumonia (INHALE 1)

July 19, 2018 updated by: Bayer

A Prospective, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of BAY 41-6551 as Adjunctive Therapy in Intubated and Mechanically-Ventilated Patients With Gram-Negative Pneumonia

To demonstrate that as adjunctive therapy to intravenous (IV) antibiotics, BAY 41-6551 400 mg (amikacin as free base) administered as an aerosol by the Pulmonary Drug Delivery System (PDDS) Clinical every 12 hours is safe and more effective than placebo (aerosolized normal saline) administered as an aerosol by the PDDS Clinical every 12 hours, in intubated and mechanically-ventilated patients with Gram-negative Pneumonia. The secondary endpoint objectives are to evaluate the superiority of aerosolized BAY 41-6551 versus aerosolized placebo in pneumonia-related mortality, the Early Clinical Response at Day 10, the days on ventilation, and the days in the intensive care unit (ICU).

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.

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.
725

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 3

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

  • Australia
      • Wollongong, Australia, 2500
    • New South Wales
      • Blacktown, New South Wales, Australia, 2148
    • Victoria
      • Clayton, Victoria, Australia, 3168
  • Brazil
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil, 30150 221
    • Sao Paulo
      • Campinas, Sao Paulo, Brazil, 13060904
      • São José do Rio Preto, Sao Paulo, Brazil
  • Canada
      • Quebec, Canada, G1V 4G5
    • Ontario
      • Kingston, Ontario, Canada
      • Ottawa, Ontario, Canada, K1H 8L6
      • Toronto, Ontario, Canada, M5T 2S8
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
  • Colombia
    • Atlántico
      • Barranquilla, Atlántico, Colombia
    • Valle Del Cauca
      • Cali, Valle Del Cauca, Colombia
  • Czechia
      • Praha 10, Czechia, 100 34
      • Zlin, Czechia, 762 75
  • Korea, Republic of
      • Seoul, Korea, Republic of, 137-701
      • Seoul, Korea, Republic of, 138-736
      • Seoul, Korea, Republic of, 136-705
  • Mexico
      • Aguascalientes, Mexico, 20000
      • San Luis Potosí, Mexico, 78240
    • Distrito Federal
      • México, D.F., Distrito Federal, Mexico, 07760
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44340
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexico, 64460
  • Philippines
      • Quezon City, Philippines, 1105
      • Quezon City, Philippines, NCR 1100
  • Taiwan
      • Kaohsiung, Taiwan, 82445
      • Tainan, Taiwan, 710
      • Taipei, Taiwan
      • Taipei, Taiwan, 11217
  • Thailand
      • Chiang Mai, Thailand, 50200
      • Khon Kaen, Thailand, 40002
  • Turkey
      • Ankara, Turkey, 06100
      • Trabzon, Turkey, 61080
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
      • Mobile, Alabama, United States, 36617
    • Arizona
      • Phoenix, Arizona, United States, 85008-4956
    • Connecticut
      • Danbury, Connecticut, United States, 06810
      • Hartford, Connecticut, United States, 06102
    • Delaware
      • Newark, Delaware, United States, 19713
    • Florida
      • Hollywood, Florida, United States, 33021-5421
      • Miami, Florida, United States, 33125
      • Tampa, Florida, United States, 33606-3508
    • Georgia
      • Atlanta, Georgia, United States, 30342
    • Illinois
      • Springfield, Illinois, United States, 62702
    • Indiana
      • Muncie, Indiana, United States, 47303
    • Iowa
      • Iowa City, Iowa, United States, 52242
    • Kentucky
      • Hazard, Kentucky, United States, 41701
    • Michigan
      • Kalamazoo, Michigan, United States, 49007
    • Missouri
      • Saint Louis, Missouri, United States, 63110-1093
      • Springfield, Missouri, United States, 65803
    • Montana
      • Butte, Montana, United States, 59701
    • Nevada
      • Las Vegas, Nevada, United States, 89109
    • New York
      • Brooklyn, New York, United States, 11215
      • Mineola, New York, United States, 10065
      • New York, New York, United States, 10065
      • New York, New York, United States, 10019
    • North Carolina
      • Asheville, North Carolina, United States, 28801
      • Greensboro, North Carolina, United States, 27401
    • Ohio
      • Cincinnati, Ohio, United States, 45267-0769
      • Cleveland, Ohio, United States, 44195
      • Cleveland, Ohio, United States, 44109-1998
      • Columbus, Ohio, United States, 43215
      • Youngstown, Ohio, United States, 44501
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73117
    • South Carolina
      • Charleston, South Carolina, United States, 29425

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males and non-pregnant, non-lactating females, 18 years of age or older
  • Intubated and mechanically-ventilated
  • Diagnosis of pneumonia defined as presence of a new or progressive infiltrate(s) on chest radiograph
  • Presence of Gram-negative organism(s) by either Gram stain or culture of respiratory secretions, or suspected Gram-negative pathogen
  • Impaired oxygenation
  • Clinical Pulmonary Infection Score (CPIS) of at least 6
  • Presence of a multi-drug resistant (MDR) organism in a pre-therapy respiratory specimen OR at least two risk factors for MDR organisms

Exclusion Criteria:

  • History of hypersensitivity to amikacin or other aminoglycosides
  • Has received antibiotic therapy for Gram-negative pneumonia for greater than 48 hours at the time of randomization
  • Known or suspected bacteremia secondary to Staphylococcus aureus
  • A positive urine and/or serum beta-human Chorionic Gonadotropin pregnancy test
  • Patients with a serum creatinine > 2 mg/dL (177 µmol/L) [Exception: Patients with a serum creatinine > 2 mg/dL (177 µmol/L) and being treated with continuous renal replacement therapy (Continuous Veno-Venous Hemodialysis and CVVHemoDiafiltration) or daily hemodialysis will receive the aerosol study drug treatment]
  • Has been on mechanical ventilation for > 28 days
  • Is participating in or has participated in other investigational interventional studies within the last 28 days prior to study treatment
  • The risk of rapidly fatal illness and death within 72 hrs, or any concomitant condition not related to ventilator-associated pneumonia that, in the opinion of the investigator, precludes completion of study evaluations and the course of therapy
  • Has an Acute Physiology and Chronic Health Evaluation (APACHE) II score < 10
  • Patients receiving veno-venous extracorporeal circulation membrane oxygenation (V-V ECMO)

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 Assignment
  • 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 inhale (BAY41-6551)
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
Drug: Amikacin Inhalation Solution (BAY41-6551)
400 mg of aerosolized amikacin every 12 hours for 10 days to be administered using the Pulmonary Drug Delivery System (PDDS Clinical)
Placebo Comparator: Placebo
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
Drug: Aerosolized Placebo
Aerosolized placebo every 12 hours for 10 days to be administered using the Pulmonary Drug Delivery System (PDDS Clinical)

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
Number of Participants Surviving Through LFU Visit
Time Frame: Up to 28-32 days after start of study treatment
The primary efficacy variable is Survival through the late follow-up (LFU) visit. Survival is achieved when the participant is alive through the LFU visit. No other factors are considered in the evaluation of survival.
Up to 28-32 days after start of study treatment

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
Number of Participants With Adjudicated Pneumonia-Related Death Through LFU Visit
Time Frame: Up to 28-32 days after start of study treatment
Death through LFU visit was adjudicated as pneumonia-related or pneumonia-unrelated for participants in the amikacin inhale group and participants in the placebo group.
Up to 28-32 days after start of study treatment
Number of Participants With Early Clinical Response
Time Frame: Up to 10 days after start of study treatment
Early Clinical Response was determined by the following: 1. CPIS scoring at Days 3, 5, and 10 compared to baseline (a. On Day 3, CPIS increase from baseline by at least 2 points was considered a failure. b. On Day 5, CPIS decrease from baseline of at least 1 point was not a failure. CPIS of no change from baseline was considered a failure. Any CPIS increase from baseline was a failure. c. On Day 10, CPIS decrease from baseline of at least 2 points was not a failure. CPIS decrease of only 1 point is a failure. Clinical Pulmonary Infection Score of no change was considered a failure. Any CPIS increase from baseline was a failure). 2. All-cause mortality through EOT visit was a failure. 3. The development of empyema or lung abscess through the EOT visit was a failure.
Up to 10 days after start of study treatment
Number of Days on Mechanical Ventilation Through LFU Visit
Time Frame: Up to 28-32 days after start of study treatment
Number of days on mechanical ventilator was summarized by descriptive statistics. Duration was defined as the number of days from the date of first study drug through the LFU visit. For participants who lived through the LFU visit, the ventilation days were actual days on ventilation with a maximum value of 28 days. For participants who died after Day 28 but on or before their LFU visit, the days on ventilator was censored at 28 days. For participants who died or discontinued off ventilation, the number of days on ventilation was actual days on ventilation with a maximum value of 28 days. For participants who died or discontinued on ventilation, the number of days on ventilation was 28 days. Further analysis of the number of days on mechanical ventilator was to be performed with censoring at Day 28 for subset of participants on ventilation without censoring.
Up to 28-32 days after start of study treatment
Number of Days in the ICU Through LFU Visit
Time Frame: Up to 28-32 days after start of study treatment
Number of days in ICU was summarized by descriptive statistics. Duration was defined as the number of days from the date of first study drug through the LFU visit. For participants who lived in ICU through the LFU visit, the ICU days were actual days in ICU with a maximum value of 28 days. For participants who died after Day 28 but on or before their LFU visit, the days in ICU was censored at 28 days. For participants who died or discontinued in ICU, the number of days in ICU was 28 days. Further analysis of the number of days in ICU was to be performed with censoring at Day 28 for subset of participants on ventilation and without censoring.
Up to 28-32 days after start of study treatment

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Time Frame: Up to 17-19 days after start of study treatment
The number of participants with microbiological response for each pathogen among the total number of participants with baseline pathogen isolates for each pathogen was determined. If a participant had 3 pathogens, all 3 were tabulated. Eradication ( defined as the absence of the original pathogen(s) at the post-treatment test-of-cure [TOC] visit culture of specimens from the original site of infection) and presumed eradication (defined as absence of appropriate culture material in a participant judged to be a clinical cure; he or she was unable to produce sputum and invasive procedures were not warranted) rates were reported to reveal the microbiological responses. The data were displayed for each bacterial genus/species. Baseline pathogen was defined as pathogens tested at Screening and Day 1 visit by central laboratory.
Up to 17-19 days after start of study treatment
Number of Participants With Microbiological Response at TOC Visit
Time Frame: Up to 17-19 days after start of study treatment
The responses of eradication (defined as the absence of the original pathogen(s) at the post-treatment TOC culture of specimens from the original site of infection) and presumed eradication (defined as absence of appropriate culture material in a participant judged to be a clinical cure; he or she was unable to produce sputum and invasive procedures were not warranted) were tabulated for each participant to reveal the microbiological responses. All pathogen isolates from a participant must be eradicated (or presumed eradicated) to tabulate an eradicated (or presumed eradicated) response. Baseline pathogen was defined as pathogens tested at Screening and Day 1 visit by central laboratory.
Up to 17-19 days after start of study treatment
Number of Participants With Microbiological Recurrence at LFU Visit
Time Frame: Up to 28-32 days after start of study treatment
The responses of recurrence were tabulated for each participant. Recurrence was defined as the reappearance of the original pathogen(s) from a specimen taken after the TOC visit. If one or more pathogen reappeared, all isolates from a participant were tabulated as "recurrence". Baseline pathogen was defined as pathogens tested at Screening and Day 1 visit by central laboratory.
Up to 28-32 days after start of study treatment
Number of Participants With Emergence of New Respiratory Pathogens During the Aerosol Treatment Period
Time Frame: Up to 10 days after start of study treatment
New pathogens also denoted as superinfection was defined as the isolation of a new pathogen (not the original baseline pathogen) from a specimen taken while the participant was on antibiotic therapy (Day 1 to EOT) and having a need for alternative antimicrobial therapy. Rates of emergence of any new pathogen by participant after start of study drug were summarized for each treatment group.
Up to 10 days after start of study treatment
Number of Participants With Emergence of Resistance Among Pathogens
Time Frame: Up to 28-32 days after start of study treatment
Resistance to amikacin was determined for the bacterial isolates by using a standardized microbiology laboratory test that generates a minimum inhibitory concentration (MIC) for amikacin and bacterial isolate. The same microbiology resistance standard was used for all bacteria tested against amikacin. Resistant bacteria have a MIC value of 64 μg/mL or greater. Percentages of resistance were calculated based on the percentage of participants infected with any treatment-emergent pathogens resistant to amikacin. If a participant had a more than one occurrence of a specific pathogen during pre-treatment period, the worst case of testing was used.
Up to 28-32 days after start of study treatment
Number of Participants Who Received at Least One Dose of Study Drug and Reported an Adverse Event
Time Frame: Up to 7 days after the end of study treatment
AE was untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. AEs, occurred any time after the first dose of therapy and through 7 days after the EOT were recorded as treat-emergent AEs (TEAEs).
Up to 7 days after the end of study treatment
Number of Participants Who Received at Least One Dose of Study Drug and Reported a Serious Adverse Event
Time Frame: Up to 7 days after the end of study treatment
AE was untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE: AE resulting in following outcomes or deemed significant for any reason: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent; significant disability/incapacity; congenital anomaly/birth defect; medical important serious event judged by investigator. SAEs, occurred any time after the first dose of therapy and through 7 days after the EOT were recorded as treat-emergent SAEs (TESAEs).
Up to 7 days after the end of study treatment
Number of Participants With Organ Failure
Time Frame: Up to 7 days after the end of study treatment
The overall number of participants with any organ failure was summarized for each treatment group. Organ failure was defined by a specific organ type and by a collection of MedDRA version 20.0 preferred terms that were determined by the sponsor's clinical team. A participant with multiple AEs within a system organ class or preferred term is counted a single time for that system organ class (SOC) or preferred term.
Up to 7 days after the end of study treatment
Number of Death Due to Any Reason Through Day 10 and Day 15
Time Frame: Up to 10 days and 15 days after start of study treatment, respectively
Number of deaths due to any reason through Day 10 and Day 15 were summarized for each treatment group.
Up to 10 days and 15 days after start of study treatment, respectively

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.
Bayer

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Nektar Therapeutics

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 (Actual)

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.
April 13, 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.
April 7, 2017

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 7, 2017

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).
February 25, 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.
February 25, 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.
February 27, 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 23, 2018

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.
July 19, 2018

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.
July 1, 2018

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.
  • 13084
  • 2013-001048-73 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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