Inhaled Amikacin Solution (BAY 41-6551) as Adjunctive Therapy in the Treatment of Gram-Negative Pneumonia (INHALE 2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Bayer
Sponsor:
Collaborator:
Nektar Therapeutics
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00805168
First received: December 8, 2008
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

To evaluate the efficacy and safety of adjunctive aerosolized BAY 41-6551 (amikacin inhalation solution) versus aerosolized placebo in the treatment of intubated and mechanically ventilated adult patients with Gram-negative pneumonia receiving standard of care intravenous antibiotics


Condition Intervention Phase
Pneumonia, Bacterial
Drug: Amikacin Inhalation Solution (BAY41-6551)
Drug: Aerosolized Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Clinical response at the Test-of-Cure (TOC) visit in the modified Intent-to-Treat (ie, ITT population plus a pre-therapy culture positive for a Gram-negative respiratory tract pathogen and an APACHE II score of at least 10) population. [ Time Frame: 17-19 days after start of treatment with study medication ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of days on mechanical ventilation through the Day 28 visit [ Time Frame: 28-32 days after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Total number of days of Gram-negative IV antibiotics per patient [ Time Frame: 17-19 days and then 28-32 days after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Number of intensive care unit (ICU) days at the Day 28 visit [ Time Frame: 28-32 days after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Number of hospital days at the Day 28 visit [ Time Frame: 28-32 days after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Clinical relapse rates at the Day 28 visit [ Time Frame: 28-32 days after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Per pathogen microbiological response rates at the TOC visit [ Time Frame: 17-19 days after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Per patient microbiological response rates at the TOC visit [ Time Frame: 17-19 days after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Microbiological recurrence rates at the TOC and Day 28 Visit [ Time Frame: 17-19 days and then 28-32 days after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Emergence of new potential respiratory pathogens during the treatment period. [ Time Frame: 17-19 days after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Emergence of resistance among baseline pathogens in those patients with persistent infection or colonization [ Time Frame: 17-19 days after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Number of patients who have received at least one dose of study drug and reported an adverse event [ Time Frame: After patient has signed Informed Consent until they have ended participation on the Study ] [ Designated as safety issue: Yes ]
  • Mortality during the treatment period, Day 15, and Day 28 visit [ Time Frame: 17-19 days and then 28-32 days after start of treatment with study medication ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 650
Study Start Date: May 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 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)
Placebo Comparator: Arm 2 Drug: Aerosolized Placebo
Aerosolized placebo every 12 hours for 10 days to be administered using the Pulmonary Drug Delivery System (PDDS Clinical)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and non-pregnant, non-lactating females, 18 years of age or older
  • Intubated and mechanically-ventilated pneumonia- 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
  • Signs of infection
  • Impaired oxygenation
  • CPIS of at least 6
  • 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 24 hours at the time of randomization
  • Primary lung cancer (including patients with small cell lung carcinoma/non-small cell lung carcinoma and patients with unknown histology) or another malignancy metastatic to the lungs or other known endobronchial obstructions Exception: Please note that patients with complete resection of non-small cell lung carcinoma are eligible for the study.
  • Known or suspected active tuberculosis, cystic fibrosis, human immunodeficiency virus (HIV) infection with CD 4 count < 200 cell/mm3, or invasive fungal infection of the lung, lung abscess, or empyema
  • Known or suspected bacteremia secondary to Staphylococcus aureus
  • Has had a stroke within five days
  • A positive urine and/or serum beta-hCG pregnancy test
  • Burns greater than 40% of total body surface area
  • 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 (CVVH and CVVH-D) or daily hemodialysis will receive the aerosol study drug treatment
  • Neutropenia (Screening ANC < 103 neutrophils/mm3), stem cell transplant
  • 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 VAP that, in the opinion of the investigator, precludes completion of study evaluations and the course of therapy
  • Stem cell transplantation
  • Patients with documented Legionella infection (eg, Legionella pneumonia)
  • Has an APACHE II score < 10
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00805168

Contacts
Contact: Bayer Clinical Trials Contact clinical-trials-contact@bayerhealthcare.com
Contact: For trial location information (Phone Menu Options '3' or '4') (+)1-888-84 22937

  Show 196 Study Locations
Sponsors and Collaborators
Bayer
Nektar Therapeutics
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00805168     History of Changes
Other Study ID Numbers: 13085, 2008-000906-35
Study First Received: December 8, 2008
Last Updated: July 7, 2014
Health Authority: United Kingdom: Department of Health
Belgium: Institutional Review Board
Germany: Ethics Commission
France: Ministry of Health
Italy: Ministry of Health
Spain: Ministry of Health
Czech Republic: Ethics Committee
Poland: Ministry of Health
Switzerland: Swiss Agency for Theraputic Products
Hungary: National Institute of Pharmacy
Netherlands: Medical Ethics Review Committee (METC)
Norway: Norwegian Medicines Agency (Statens legemiddelverk, NOMA)Russia: Ethics Committee
Ukraine: Ministry of Health
China: Ministry of Health
Greece: Ethics Committee
Israel: Ministry of Health
Japan: Institutional Review Board
Turkey: Ministry of Health
Portugal: The National Institute of Pharmacy and Medicines (Infarmed)

Keywords provided by Bayer:
Gram-negative Pneumonia
Pneumonia
Intubation
Mechanical ventilation
Amikacin

Additional relevant MeSH terms:
Pneumonia, Bacterial
Pneumonia
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Amikacin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014