Clinical trial NCT01799993: Inhaled Amikacin Solution BAY41-6551 as Adjunctive Therapy in the Treatment of Gram-Negative Pneumonia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia, Bacterial
Keywords: Gram-negative pneumonia
Intubation
Mechanical ventilation
Amikacin
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Nektar Therapeutics
First posted: 2013-02-27
Enrollment: 725
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants Surviving Through LFU Visit
timeFrame: Up to 28-32 days after start of study treatment
Secondary outcomes:
measure: Number of Participants With Adjudicated Pneumonia-Related Death Through LFU Visit
timeFrame: Up to 28-32 days after start of study treatment
measure: Number of Participants With Early Clinical Response
timeFrame: Up to 10 days after start of study treatment
measure: Number of Days on Mechanical Ventilation Through LFU Visit
timeFrame: Up to 28-32 days after start of study treatment
measure: Number of Days in the ICU Through LFU Visit
timeFrame: Up to 28-32 days after start of study treatment
Other outcomes:
measure: Number of Participants With Microbiological Response Per Pathogen at TOC Visit
timeFrame: Up to 17-19 days after start of study treatment
measure: Number of Participants With Microbiological Response at TOC Visit
timeFrame: Up to 17-19 days after start of study treatment
measure: Number of Participants With Microbiological Recurrence at LFU Visit
timeFrame: Up to 28-32 days after start of study treatment
measure: Number of Participants With Emergence of New Respiratory Pathogens During the Aerosol Treatment Period
timeFrame: Up to 10 days after start of study treatment
measure: Number of Participants With Emergence of Resistance Among Pathogens
timeFrame: Up to 28-32 days after start of study treatment
measure: Number of Participants Who Received at Least One Dose of Study Drug and Reported an Adverse Event
timeFrame: Up to 7 days after the end of study treatment
measure: Number of Participants Who Received at Least One Dose of Study Drug and Reported a Serious Adverse Event
timeFrame: Up to 7 days after the end of study treatment
measure: Number of Participants With Organ Failure
timeFrame: Up to 7 days after the end of study treatment
measure: Number of Death Due to Any Reason Through Day 10 and Day 15
timeFrame: Up to 10 days and 15 days after start of study treatment, respectively
Locations:
city: Birmingham
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Danbury
country: United States
state: Connecticut
city: Hartford
country: United States
state: Connecticut
city: Newark
country: United States
state: Delaware
city: Hollywood
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Springfield
country: United States
state: Illinois
city: Muncie
country: United States
state: Indiana
city: Iowa City
country: United States
state: Iowa
city: Hazard
country: United States
state: Kentucky
city: Kalamazoo
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Springfield
country: United States
state: Missouri
city: Butte
country: United States
state: Montana
city: Las Vegas
country: United States
state: Nevada
city: Brooklyn
country: United States
state: New York
city: Mineola
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Youngstown
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Charleston
country: United States
state: South Carolina
city: Blacktown
country: Australia
state: New South Wales
city: Clayton
country: Australia
state: Victoria
city: Wollongong
country: Australia
city: Belo Horizonte
country: Brazil
state: Minas Gerais
city: Campinas
country: Brazil
state: Sao Paulo
city: São José do Rio Preto
country: Brazil
state: Sao Paulo
city: Kingston
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Barranquilla
country: Colombia
state: Atlántico
city: Cali
country: Colombia
state: Valle Del Cauca
city: Praha 10
country: Czechia
city: Zlin
country: Czechia
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: México, D.F.
country: Mexico
state: Distrito Federal
city: Guadalajara
country: Mexico
state: Jalisco
city: Monterrey
country: Mexico
state: Nuevo Leon
city: Aguascalientes
country: Mexico
city: San Luis Potosí
country: Mexico
city: Quezon City
country: Philippines
city: Quezon City
country: Philippines
city: Kaohsiung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Chiang Mai
country: Thailand
city: Khon Kaen
country: Thailand
city: Ankara
country: Turkey
city: Trabzon
country: Turkey
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.