Inhaled Amikacin Solution (BAY 41-6551) as Adjunctive Therapy in the Treatment of Gram-Negative Pneumonia

Pneumonia, Bacterial Clinical Trial

— INHALE 2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00805168
• Other study ID #: 13085
• Secondary ID: 2008-000906-35
• Status: Completed
• Phase: Phase 3
• First received: December 8, 2008
• Last updated: December 12, 2017
• Start date: May 28, 2013
• Est. completion date: April 7, 2017

Study information

• Verified date: December 2017
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 461
• Est. completion date: April 7, 2017
• Est. primary completion date: April 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 or at least two risk factors for multi-drug resistant 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 umol/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)

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Bacterial

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Bayer	Nektar Therapeutics, Novartis Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  China,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Netherlands,  Poland,  Portugal,  Russian Federation,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of patients who received at least one dose of study drug and reported an adverse event		35-39 days after start of study treatment
Other	Number of patients who received at least one dose of study drug and reported a serious adverse event		28-32 days after start of study treatment
Other	Progression and incidence rates of organ failure		28-32 days after start of study treatment
Other	All-cause mortality rate		10 days and 15 days after start of study treatment, respectively
Primary	Survival through the late follow-up (LFU) visit		28-32 days after start of study treatment
Secondary	Pneumonia-related mortality through the LFU visit		28-32 days after start of study treatment
Secondary	Early Clinical Response based on Clinical Pulmonary Infection Score (CPIS) scores, the presence of empyema or lung abscess, and all-cause mortality through end of therapy (EOT) visit		10 days after start of study treatment
Secondary	Number of days on mechanical ventilation through the LFU visit		28-32 days after start of study treatment
Secondary	Number of days in the ICU through the LFU visit		28-32 days after start of study treatment
Secondary	Per pathogen microbiological response rates at the Test-of-Cure (TOC) visit		17-19 days after start of study treatment
Secondary	Per patient microbiological response rates at the TOC visit		17-19 days after start of study treatment
Secondary	Microbiological recurrence rates at the TOC and LFU visits		17-19 days and 28-32 days after start of study treatment, respectively
Secondary	Emergence of new respiratory pathogens during the aerosol treatment period		10 days after start of study treatment
Secondary	Emergence of resistance among baseline pathogens in those patients with persistent infection or colonization		28-32 days after start of study treatment

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