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

NCT01799993 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 130842013-001048-73
• Study Type: interventional
• Target: 725
• Locations: 12 countries
• Sites: 65

Brief Summary

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).

Conditions

Pneumonia, Bacterial

Keywords

Gram-negative pneumonia; Intubation; Mechanical ventilation; Amikacin

Outcome Measures

Primary Outcomes (1)

• Number of Participants Surviving Through LFU Visit

  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 Outcomes (4)

• Number of Participants With Adjudicated Pneumonia-Related Death Through LFU Visit

  Up to 28-32 days after start of study treatment

• Number of Participants With Early Clinical Response

  Up to 10 days after start of study treatment

• Number of Days on Mechanical Ventilation Through LFU Visit

  Up to 28-32 days after start of study treatment

• Number of Days in the ICU Through LFU Visit

  Up to 28-32 days after start of study treatment

Other Outcomes (9)

• Number of Participants With Microbiological Response Per Pathogen at TOC Visit

  Up to 17-19 days after start of study treatment

• Number of Participants With Microbiological Response at TOC Visit

  Up to 17-19 days after start of study treatment

• Number of Participants With Microbiological Recurrence at LFU Visit

  Up to 28-32 days after start of study treatment

Study Arms (2)

Amikacin inhale (BAY41-6551)

EXPERIMENTAL

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)

Placebo

PLACEBO COMPARATOR

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

Drug: Aerosolized Placebo

Interventions

Amikacin Inhalation Solution (BAY41-6551) DRUG

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

Amikacin inhale (BAY41-6551)

Aerosolized Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Bayer: lead
• Nektar Therapeutics: collaborator

Study Sites (65)

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Birmingham, Alabama, 35233, United States

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Mobile, Alabama, 36617, United States

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Phoenix, Arizona, 85008-4956, United States

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Danbury, Connecticut, 06810, United States

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Hartford, Connecticut, 06102, United States

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Newark, Delaware, 19713, United States

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Hollywood, Florida, 33021-5421, United States

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Miami, Florida, 33125, United States

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Tampa, Florida, 33606-3508, United States

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Atlanta, Georgia, 30342, United States

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Springfield, Illinois, 62702, United States

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Muncie, Indiana, 47303, United States

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Iowa City, Iowa, 52242, United States

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Hazard, Kentucky, 41701, United States

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Kalamazoo, Michigan, 49007, United States

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Springfield, Missouri, 65803, United States

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St Louis, Missouri, 63110-1093, United States

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Butte, Montana, 59701, United States

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Las Vegas, Nevada, 89109, United States

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Brooklyn, New York, 11215, United States

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Mineola, New York, 10065, United States

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New York, New York, 10019, United States

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New York, New York, 10065, United States

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Asheville, North Carolina, 28801, United States

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Greensboro, North Carolina, 27401, United States

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Cincinnati, Ohio, 45267-0769, United States

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Cleveland, Ohio, 44109-1998, United States

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Cleveland, Ohio, 44195, United States

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Columbus, Ohio, 43215, United States

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Youngstown, Ohio, 44501, United States

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Oklahoma City, Oklahoma, 73117, United States

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Charleston, South Carolina, 29425, United States

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Blacktown, New South Wales, 2148, Australia

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Clayton, Victoria, 3168, Australia

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Wollongong, 2500, Australia

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Belo Horizonte, Minas Gerais, 30150 221, Brazil

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Campinas, São Paulo, 13060904, 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, K1H 8L6, Canada

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Toronto, Ontario, M5T 2S8, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Québec, G1V 4G5, Canada

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Barranquilla, Atlántico, Colombia

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Cali, Valle del Cauca Department, Colombia

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Prague, 100 34, Czechia

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Zlín, 762 75, Czechia

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Guadalajara, Jalisco, 44340, Mexico

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México, D.F., Mexico City, 07760, Mexico

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Monterrey, Nuevo León, 64460, Mexico

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Aguascalientes, 20000, Mexico

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San Luis Potosí City, 78240, Mexico

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Quezon City, 1105, Philippines

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Quezon City, NCR 1100, Philippines

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Seoul, 136-705, South Korea

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Seoul, 137-701, South Korea

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Seoul, 138-736, South Korea

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Kaohsiung City, 82445, Taiwan

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Tainan, 710, Taiwan

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Taipei, 11217, Taiwan

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Taipei, Taiwan

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Chiang Mai, 50200, Thailand

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Khon Kaen, 40002, Thailand

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Ankara, 06100, Turkey (Türkiye)

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Trabzon, 61080, Turkey (Türkiye)

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Related Publications (1)

• 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.

  PMID: 31866328 DERIVED

Related Links

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

MeSH Terms

Conditions

Pneumonia, Bacterial

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

To shorten the time required to obtain data from the 2 clinical studies of Amikacin Inhale Phase 3 program, Bayer and the FDA decided that the results of studies NCT01799993 and NCT00805168 should be consolidated into a single report.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: February 25, 2013
• First Posted: February 27, 2013
• Study Start: April 13, 2013
• Primary Completion: April 7, 2017
• Study Completion: April 7, 2017
• Last Updated: July 23, 2018
• Results First Posted: June 26, 2018

Record last verified: 2018-07

Locations

US (32); TH (2); AU (3); CZ (2); TU (2); BR (3); ME (5); CA (5); PH (2); KR (3); TW (4); CO (2)