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

NCT ID: NCT01799993

Last Updated: 2018-07-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

725 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-13

Study Completion Date

2017-04-07

Brief Summary

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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).

Detailed Description

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Conditions

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Pneumonia, Bacterial

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Amikacin Inhalation Solution (BAY41-6551)

Intervention Type DRUG

400 mg of aerosolized amikacin every 12 hours for 10 days to be administered using the Pulmonary Drug Delivery System (PDDS Clinical)

Placebo

Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.

Group Type PLACEBO_COMPARATOR

Aerosolized Placebo

Intervention Type DRUG

Aerosolized placebo every 12 hours for 10 days to be administered using the Pulmonary Drug Delivery System (PDDS Clinical)

Interventions

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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)

Intervention Type DRUG

Aerosolized Placebo

Aerosolized placebo every 12 hours for 10 days to be administered using the Pulmonary Drug Delivery System (PDDS Clinical)

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nektar Therapeutics

INDUSTRY

Sponsor Role collaborator

Bayer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

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Birmingham, Alabama, United States

Site Status

Mobile, Alabama, United States

Site Status

Phoenix, Arizona, United States

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Danbury, Connecticut, United States

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Hartford, Connecticut, United States

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Newark, Delaware, United States

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Hollywood, Florida, United States

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Miami, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Springfield, Illinois, United States

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Muncie, Indiana, United States

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Iowa City, Iowa, United States

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Hazard, Kentucky, United States

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Kalamazoo, Michigan, United States

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Springfield, Missouri, United States

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St Louis, Missouri, United States

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Butte, Montana, United States

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Las Vegas, Nevada, United States

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Brooklyn, New York, United States

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Mineola, New York, United States

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New York, New York, United States

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New York, New York, United States

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Asheville, North Carolina, United States

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Greensboro, North Carolina, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Youngstown, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Charleston, South Carolina, United States

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Blacktown, New South Wales, Australia

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Clayton, Victoria, Australia

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Wollongong, , Australia

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Belo Horizonte, Minas Gerais, Brazil

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Campinas, São Paulo, Brazil

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São José do Rio Preto, São Paulo, Brazil

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Kingston, Ontario, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, , Canada

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Barranquilla, Atlántico, Colombia

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Cali, Valle del Cauca Department, Colombia

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Prague, , Czechia

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Zlín, , Czechia

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Guadalajara, Jalisco, Mexico

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México, D.F., Mexico City, Mexico

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Monterrey, Nuevo León, Mexico

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Aguascalientes, , Mexico

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San Luis Potosí City, , Mexico

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Quezon City, , Philippines

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Quezon City, , Philippines

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Kaohsiung City, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Chiang Mai, , Thailand

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Khon Kaen, , Thailand

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Ankara, , Turkey (Türkiye)

Site Status

Trabzon, , Turkey (Türkiye)

Site Status

Countries

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United States Australia Brazil Canada Colombia Czechia Mexico Philippines South Korea Taiwan Thailand Turkey (Türkiye)

References

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Niederman MS, Alder J, Bassetti M, Boateng F, Cao B, Corkery K, Dhand R, Kaye KS, Lawatscheck R, McLeroth P, Nicolau DP, Wang C, Wood GC, Wunderink RG, Chastre J. Inhaled amikacin adjunctive to intravenous standard-of-care antibiotics in mechanically ventilated patients with Gram-negative pneumonia (INHALE): a double-blind, randomised, placebo-controlled, phase 3, superiority trial. Lancet Infect Dis. 2020 Mar;20(3):330-340. doi: 10.1016/S1473-3099(19)30574-2. Epub 2019 Dec 19.

Reference Type DERIVED
PMID: 31866328 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.clinicaltrialsregister.eu/

Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

Other Identifiers

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2013-001048-73

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

13084

Identifier Type: -

Identifier Source: org_study_id

NCT00805168

Identifier Type: -

Identifier Source: nct_alias

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