Intensive care unit patients with ventilation-associated pneumonia. MedDRA version: 20.1 Level: LLT Classification code 10065153 Term: Ventilator associated pneumonia System Organ Class: 100000004862
Conditions
Interventions
Trade Name: TOBI®
Product Name: Tobramycin
Product Code: TBM100B
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: Tobramycin
CAS Number: 32986-56-4
Current Sponsor code: Tobi
Other descrip
Sponsors
Charité University Hospital Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - male or female subjects aged = 18 and = 85 years at the time of screening - legal care by an appropriate legal guardian has been set prior any study related procedure unless the patient can give his own written informed consent - written informed consent form signed by patient and if appropriate by parent/legal guardians, prior to any study-related procedure - ventilated patient with ventilator-associated pneumonia (VAP; definition VAP according to Luna et al., 2003 and Dalhoff et al. 2012) - reasonable suspicion of gram-negative bacteria in pulmonary infiltrate (gram-negativity diagnosed by gram stain preparation, PCR technologies or kinetic laser measurement of turbidity increase of particles (diagnosis is made within 24 hours) - patient must be able to receive either one of the two arms of treatment defined for the study - patient was treated shorter than 48 hours with standard systemic antibiotic therapy before the diagnosis of VAP - enrolment of patients with therapy-refractive VAP possible (within 6 days after start of new systemic antibiotic therapy) 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 11 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: - patients do not match the criteria for inclusion - chronic colonisation with non-fermenting organisms which was known before hospitalization of the patient and which was verified at least twice at an interval of 4 weeks - known local or systemic hypersensitivity to aminoglycosides, inhaled antibiotics, to drugs with similar chemical structures or other ingredients of the trial medication - patients who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml)) - history of severe clinical relevant bronchospasm - severe active hemoptysis of more than 60 cc (60 ml) at any time within 30 days prior to study drug administration - tinnitus treated in the last 3 months before enrollment - treatment with mannitol in the last 24 h before enrollment - treatment with drugs5 that might unfavorably interact with TOBI® - patients with cystic fibrosis, acquired immune deficiency syndrome (AIDS), neutropenia, active tuberculosis, or patients taking immunosuppressive therapy in preparation for or following an organ transplant - antibiotic treatment (except surgical antibiotic prophylaxis following national guidelines) according to the following terms: o systemic antibiotics against VAP that helped to treat this VAP successfully o use of antibiotics not authorized in the study (all inhalative antibiotics including off-label use of antibiotics: e.g. amphotericin b, colistin, ciprofloxacin, levofloxacin, ceftazidime, meropenem) - patients who are included in another intervention study or who have been part of another intervention study 30 days before entry into this study - lack of written informed consent by the patient or his legal guardian - patients with other underlying conditions6 that may have a significant effect on the target variables and would make it difficult to interpret response to study drug - patients with deteriorating general condition (maximal survival expectance < 6 weeks) - persons held or being hospitalized in an institution by legal or official order (according to AMG § 40(1)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is the reduction and eradication of the endobronchial gram-negative bacteria in the pulmonal system, assessed as eradication of the pathogen at day 6 measured by the decrease in gram-negative pathogen-load in pulmonary infiltrate (either by gram-staining of the pathogen, by measurement of copies of DNA per ml in end-point PCR analysis or by kinetic laser measurement of turbidity increase of particles).;Secondary Objective: The safety of the therapy with TOBI® or aerosolized sodium chloride solution will be assessed each day of the study by physical examination, vital signs, laboratory tests and evaluation of adverse events. Furthermore, the patient will be monitored for spontaneous complaints after treatment with TOBI® or aerosolized sodium chloride solution (control group). ;Primary end point(s): Eradication of the gram-negative pathogen (two days after termination of inhalation treatment, day 6);Timepoint(s) of evaluation of this end point: Day 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): A) eradication of the gram-negative pathogen B) length of stay in ICU (at final visit) C) clinical cure of pneumonia D) duration of systemic antibiotic treatment for pneumonia E) systemic antibiotic-free days F) duration of ventilation for pneumonia G) ventilator-free days H) reinfection3 of pneumonia caused by the same verified pathogen (at discharge from ICU);Timepoint(s) of evaluation of this end point: For secondary endpoint A) - two days after termination of systemic antibiotic treatment For secondary endpoint B) - at final visit (at maximum day 90 after enrollment) For secondary endpoint C) - each day until two days after termination of systemic antibiotic treatment For secondary endpoint D) - at discharge from ICU For secondary endpoint E) - at discharge from ICU For secondary endpoint F) - at discharge from ICU For secondary endpoint G) - at discharge from ICU For secondary endpoint H) - at discharge from ICU | — |
Countries
Germany
Contacts
Public ContactDr. Carsten Schwarz
Charité University Hospital Berlin
Outcome results
None listed