Gram-negaive pneumonia MedDRA version: 16.1 Level: LLT Classification code 10035701 Term: Pneumonia gram-negative bacterial NOS System Organ Class: 100000004862
Conditions
Interventions
Product Name: Amikacin Sulfate 1:1.8 Solution for Inhalation
Product Code: BAY41-6551
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: Amikacin
Current Sponsor code: BAY41-6551
Other descr
Sponsors
Bayer Healthcare AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and non-pregnant, non-lactating females, 18 years of age or older. For females of child-bearing potential, one of the following medically acceptable contraceptive methods must be used: or they agree to abstain from heterosexual intercourse while participating in the study. One or more of these methods should be used during the study and continue for 30 days after completion of the antibiotic therapy. a) Double-barrier methods of contraception (eg, condoms plus spermicidal foam) b) Intrauterine contraceptive device c) Approved pharmaceutical contraceptive product (eg, birth control pills or patches, long-term injectable or implantable hormonal contraceptive) 2. Intubated and mechanically-ventilated (patients who have had a tracheotomy may be considered as possible study participants as long as they are being mechanically ventilated) 3. Diagnosis of pneumonia defined as presence of a new or progressive infiltrate(s) on chest radiograph 4. Presence of Gram-negative organism(s) indicated by: a) Gram-stain OR b) Culture of pre-therapy respiratory specimen (eg, acceptable TA, BAL, mini-BAL, PSB) 5. At least two of the following: signs of infection: a) Fever, defined as an oral temperature of > 38.0°C (100.4°F) or a tympanic/ rectal/core temperature > 38.5°C (101.3°F), or hypothermia, defined as a tympanic/rectal/core body temperature of 15% regardless of the peripheral leukocyte count c) New onset of purulent sputum or respiratory secretions, or a change in the character of sputum 6. Impaired oxygenation as demonstrated by the following: a) A decrease in PaO2/FiO2 by at least 50 mm Hg compared to a PaO2/FiO2 value within the last 48 hours from enrollment OR b) PaO2/FiO2 value of 10%) of antibiotic resistance in the community or in the specific hospital unit d) Immunosuppressive disease and/or therapy e) Presence of the risk factors for HCAP • Hospitalization for two days or more in the preceding 90 days • Residence in a nursing home or extended care facility • Home infusion therapy (including antibiotics) • Chronic dialysis within 30 days • Home wound care • Family member with multidrug-resistant pathogen 9. Be willing and able to give written informed consent. If the patient is unable to give written informed consent, the patient's legally authorized representative (LAR) may provide written consent as approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 500 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: 1. A history of hypersensitivity to amikacin or other aminoglyosides, 2. Has received antibiotic therapy for Gram-negative pneumonia for greater than 24 hours at the time of study drug administration. (There should be as minimal a time delay as possible between randomization and first dose of study drug but up to 24 hours will be acceptable. However, sites should still take into account that patients cannot receive more than 24 hours of prior antibiotic therapy for the current episode of Gram-negative pneumonia up to the time of study drug administration [not to the time of randomization]). Exceptions: Systemic antibiotic therapy for more than 24 hours in the 48 hours prior to enrollment is permitted in case the infection is caused by microbiologically-confirmed pathogens that are resistant to the antimicrobial agent used to treat the current episode of Gram-negative pneumonia. 3. Has 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: Note that patients with complete resection of non-small cell lung carcinoma are eligible for the study. 4. Known or suspected active tuberculosis, cystic fibrosis, human immunodeficiency virus (HIV) infection with CD 4 count 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 hemofiltration [CVVH] and continuous venovenous hemofiltration with dialysis [CVVH-D]) or daily hemodialysis will receive the aerosol study drug treatment (Section 8.4.6.1). 11. Neutropenia (Screening absolute neutrophil count [ANC] 28 days (ie, current event should not be more than 28 continuous days). A patient is not considered extubated if extubation lasts less than 24 hours. 13. Is participating in or has participated in other investigational interventional studies within the previous 28 days 14. The risk of rapidly fatal illness and death within 72 hours, or any concomitant conditions not related to VAP that, in the opinion of the investigator, precludes completion of study eval
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy (superiority) and safety of BAY 41-6551 as measured by the comparison of the clinical cure rate of aerosolized BAY 41-6551, administered via the PDDS Clinical, versus placebo (normal saline) at the TOC visit in patients with microbiologically confirmed Gram negative pneumonia.;Secondary Objective: The secondary efficacy objectives include: • The number of days on mechanical ventilation • The number of ICU days at Day 28 • The total number of days of Gram-negative IV antibiotics per patient • Clinical Pulmonary Infection Score (CPIS) changes to TOC • The clinical relapse rates at Day 28 • The all cause mortality rate during therapy, at day 15 and 28 Other objectives: • To determine that the PDDS Clinical device performs as intended Safety Objectives: • The frequency of AEs • The progression and incidence rates of organ failure • The all cause mortality rate during therapy, at Day 15 and 28 Secondary microbiological objectives include: • per pathogen microbiological response rates at the TOC visit • per patient microbiological response rate at the TOC visit • microbiological recurrence rates at the TOC and Day 28 visit • emergence of new respiratory pathogens during the treatment period A full list is presented in the protocol.;Primary end point(s): The primary efficacy variable will be the 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 respiratory tract pathogen) population.;Timepoint(s) of evaluation of this end point: TOC visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: 1. the number of days on mechanical ventilation through the day 28 visit 2. the number of ICU days at day 28 visit 3. the total number of days of Gram-negative IV antibiotics per patient 4. change in CPIS from the first day of study drug to TOC 5. Number of Hospital days at the day 28 visit 6. Clinical relapse rates at the day 28 visit The safety endpoints are to compare (BAY 41-6551 vs placebo) as measured by: 1. The frequency of AEs 2. The progression and incidence rates of organ failure 3. The all cause mortality rate during therapy, at Day 15 and at Day 28;Timepoint(s) of evaluation of this end point: Secondary efficacy endpoints: 1-3, 5 and 6: days 1-28. 4: TOC visit Safety endpoints: 1, 2: throughout the study 3: days 15 and at Day 28 | — |
Countries
Belgium, China, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Japan, Latvia, Netherlands, Norway, Poland, Portugal, Russian Federation, Spain, Thailand, Ukraine, United Kingdom
Contacts
Public ContactBayer Clinical Trials Contact
Bayer Healthcare AG
Outcome results
None listed