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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 November 2016 by Bayer
Sponsor:
Collaborators:
Nektar Therapeutics
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00805168
First received: December 8, 2008
Last updated: November 15, 2016
Last verified: November 2016
  Purpose
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).

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:
  • Proportion of patients deemed to be clinical successes in the BAY41-6551 treatment group divided by the proportion of cured patients in the placebo treatment group [ Time Frame: Late follow-up (LFU) visit (day 28-32) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pneumonia-related mortality through the LFU visit [ Time Frame: 28-32 days after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Early Clinical Response which is based on CPIS scores, the presence of empyema or lung abscess, and all-cause mortality [ Time Frame: Assessed through day 10 ] [ Designated as safety issue: No ]
    Early Clinical Response success occurs if there is no rise of 2 points or more on Day 3, and a drop of 1 or more points on Day 5 and a drop 2 or more points on Day 10, and the absence of lung abscess or empyema by Day 10, and alive on Day 10.

  • Number of days on mechanical ventilation through the LFU visit [ Time Frame: 28-32 days after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Number of days in the ICU through the LFU visit [ Time Frame: 28-32 days after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Number of patients who received at least one dose of study drug and reported an adverse event [ Time Frame: 35-39 days after start of treatment with study medication ] [ Designated as safety issue: Yes ]
  • Number of patients who received at least one dose of study drug and reported a serious adverse event [ Time Frame: 28-32 days after start of treatment with study medication ] [ Designated as safety issue: Yes ]
  • Progression and incidence rates of organ failure [ Time Frame: 28-32 days after start of treatment with study medication ] [ Designated as safety issue: Yes ]
  • All-cause mortality rate [ Time Frame: 28-32 days after start of treatment with study medication ] [ Designated as safety issue: Yes ]
  • Identification of laboratory data outside normal ranges [ Time Frame: 28-32 days after start of treatment with study medication ] [ Designated as safety issue: Yes ]
  • Per pathogen microbiological response rates at the Test-of-Cure (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 LFU visits [ Time Frame: 17-19 days and 28-32 days respectively after start of treatment with study medication ] [ Designated as safety issue: No ]
  • Emergence of new respiratory pathogens during the aerosol treatment period [ Time Frame: Days 1-10 ] [ Designated as safety issue: No ]
  • Emergence of resistance among baseline pathogens in those patients with persistent infection or colonization [ Time Frame: 28-32 days after start of treatment with study medication ] [ Designated as safety issue: No ]

Estimated Enrollment: 724
Study Start Date: May 2013
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (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   (Adult, Senior)
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
  • 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)
  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@bayer.com

  Show 222 Study Locations
Sponsors and Collaborators
Bayer
Nektar Therapeutics
Novartis Pharmaceuticals
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
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: November 15, 2016
Health Authority: Belgium: Institutional Review Board
Germany: Ethics Commission
France: Ministry of Health
Spain: Ministry of Health
Poland: Ministry of Health
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
Portugal: The National Institute of Pharmacy and Medicines (Infarmed)
United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Pneumonia
Pneumonia, Bacterial
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Bacterial Infections
Pharmaceutical Solutions
Amikacin
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on December 09, 2016