Inhaled Amikacin Solution BAY41-6551 as Adjunctive Therapy in the Treatment of Gram-Negative Pneumonia (INHALE 1)

Bayer

Status and phase: Completed; Phase 3

Conditions: Pneumonia, Bacterial

Treatments: Drug: Amikacin Inhalation Solution (BAY41-6551); Drug: Aerosolized Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01799993

2013-001048-73 (EudraCT Number)

13084

Details and patient eligibility

About

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).

Enrollment: 725 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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725 participants in 2 patient groups, including a placebo group

Amikacin inhale (BAY41-6551)

Experimental group

Description:

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.

Treatment:

Drug: Amikacin Inhalation Solution (BAY41-6551)

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Aerosolized Placebo