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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01799993




Registration number
NCT01799993
Ethics application status
Date submitted
25/02/2013
Date registered
27/02/2013
Date last updated
23/07/2018

Titles & IDs
Public title
Inhaled Amikacin Solution BAY41-6551 as Adjunctive Therapy in the Treatment of Gram-Negative Pneumonia
Scientific 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
Secondary ID [1] 0 0
2013-001048-73
Secondary ID [2] 0 0
13084
Universal Trial Number (UTN)
Trial acronym
INHALE 1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pneumonia, Bacterial 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Amikacin Inhalation Solution (BAY41-6551)
Treatment: Drugs - Aerosolized Placebo

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.

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


Treatment: Drugs: 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)

Treatment: Drugs: Aerosolized Placebo
Aerosolized placebo every 12 hours for 10 days to be administered using the Pulmonary Drug Delivery System (PDDS Clinical)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Surviving Through LFU Visit
Timepoint [1] 0 0
Up to 28-32 days after start of study treatment
Secondary outcome [1] 0 0
Number of Participants With Adjudicated Pneumonia-Related Death Through LFU Visit
Timepoint [1] 0 0
Up to 28-32 days after start of study treatment
Secondary outcome [2] 0 0
Number of Participants With Early Clinical Response
Timepoint [2] 0 0
Up to 10 days after start of study treatment
Secondary outcome [3] 0 0
Number of Days on Mechanical Ventilation Through LFU Visit
Timepoint [3] 0 0
Up to 28-32 days after start of study treatment
Secondary outcome [4] 0 0
Number of Days in the ICU Through LFU Visit
Timepoint [4] 0 0
Up to 28-32 days after start of study treatment

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/04/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/04/2017
Sample size
Target
Accrual to date
Final
725
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
- Blacktown
Recruitment hospital [2] 0 0
- Clayton
Recruitment hospital [3] 0 0
- Wollongong
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Delaware
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
Montana
Country [14] 0 0
United States of America
State/province [14] 0 0
Nevada
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oklahoma
Country [19] 0 0
United States of America
State/province [19] 0 0
South Carolina
Country [20] 0 0
Brazil
State/province [20] 0 0
Minas Gerais
Country [21] 0 0
Brazil
State/province [21] 0 0
Sao Paulo
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
Country [23] 0 0
Canada
State/province [23] 0 0
Quebec
Country [24] 0 0
Colombia
State/province [24] 0 0
Atlántico
Country [25] 0 0
Colombia
State/province [25] 0 0
Valle Del Cauca
Country [26] 0 0
Czechia
State/province [26] 0 0
Praha 10
Country [27] 0 0
Czechia
State/province [27] 0 0
Zlin
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Seoul
Country [29] 0 0
Mexico
State/province [29] 0 0
Distrito Federal
Country [30] 0 0
Mexico
State/province [30] 0 0
Jalisco
Country [31] 0 0
Mexico
State/province [31] 0 0
Nuevo Leon
Country [32] 0 0
Mexico
State/province [32] 0 0
Aguascalientes
Country [33] 0 0
Mexico
State/province [33] 0 0
San Luis Potosí
Country [34] 0 0
Philippines
State/province [34] 0 0
Quezon City
Country [35] 0 0
Taiwan
State/province [35] 0 0
Kaohsiung
Country [36] 0 0
Taiwan
State/province [36] 0 0
Tainan
Country [37] 0 0
Taiwan
State/province [37] 0 0
Taipei
Country [38] 0 0
Thailand
State/province [38] 0 0
Chiang Mai
Country [39] 0 0
Thailand
State/province [39] 0 0
Khon Kaen
Country [40] 0 0
Turkey
State/province [40] 0 0
Ankara
Country [41] 0 0
Turkey
State/province [41] 0 0
Trabzon

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Nektar Therapeutics
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT01799993
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01799993