Ventilator- associated pneumonia due to suspected or documented Pseudomonas aeruginosa infection.
Conditions
Sponsors
Polyphor Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male* and female** patients ?18 years of age diagnosed with VAP, i.e., pneumonia that arises more than 96 hours after endotracheal intubation documented or suspected to be due to Pseudomonas aeruginosa requiring treatment with SoC anti-pseudomonas antibiotics. 2.Patients should have a new or progressive pulmonary infiltrates on the chest radiograph attributable to pulmonary infection. AND any 2 of the following: - documented fever, defined as an oral or tympanic temperature greater than or equal to ? 38 degrees Celsius or hypothermia, defined as a core body temperature less than 35 degrees Celsius. - an elevated total peripheral white blood cell (WBC) count (WBC greater than 10,000/mm3) or greater than 15% immature neutrophils (bands), regardless of total peripheral WBC count or leukopenia with total WBC greater than 1,000/mm.3 - new onset of expectorated or suctioned respiratory secretion characterized by purulent appearance indicative of bacterial pneumonia. AND In addition, patients must have Clinical Pulmonary Infection Score of ? 6. 3.Respiratory specimen taken by endotracheal (ETA) aspirate, suitable for quantitative cultures as well as for performing Gram stain (In addition a rapid diagnosis test will be performed on the baseline ETA from Greece sites, wherever possible). 4.BAL or mini-BAL sample taken (if there is a medical indication to perform BAL or it is part of the routine protocol in the patient management at the study site for quantitative culture and rapid diagnostic test at baseline). 5.Venous access available for IV dosing. 6.Informed consent: i.If the patient is unable to comprehend the scope of the trial prior to enrolment due to altered mental status associated with the underlying pneumonia or any other disease: written informed consent to participate in the study must be obtained from the patient?s legally acceptable representative or a relative, as required by national laws, respective regulations and Institutional Review Boards/Independent Ethics Committees/Regional Ethics Boards (IRB/IEC/REB). (Written informed consent should be sought from the patient as soon as he/she becomes capable of comprehending the scope of the trial). 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1.Patients with known hypersensitivity to flouroquinolones, carbapenems, cephalosporin, penicillin (beta-lactam antibiotics) or aminoglycoside antibiotics (i.e. all available SoC antibiotics); patients with a clinically significant history of drug allergies and history of anaphylactic reaction and patients with active allergic conditions at the time of screening. 2.Patients who received more than 24 hours of anti-pseudomonas antibiotic(s) for the current VAP 3.Female patients who are pregnant or breast feeding; 4.Known or suspected pulmonary conditions which are likely to interfere with the therapeutic response or might have additional impact on pharmacokinetics (volume of distribution), such as: i. evidence of active tuberculosis or other mycobacterium infections, ii. cystic fibrosis, iii. bronchial obstruction, iv. post-obstructive pneumonia due to reasons other than chronic obstructive pulmonary disease (COPD), v. known or suspected Pneumocystis jiroveci (Pneumocystis carinii) infection, vi. granulomatous disease, vii. lung cancer or another malignancy metastatic to the lungs, viii. acute respiratory distress syndrome (ARDS) with the underlying cause other than pneumonia, ix. empyema. 5.Patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) score >25. 6.Presence of septic shock at the time of evaluation for study entry defined as acute occurrence of non-pulmonary organ dysfunctions or acute worsening of chronic non-pulmonary organ dysfunction within the last 48 hours that is not attributable to an alternative process. 7.History of lung transplant. 8.Known or suspected Legionella pneumophilia pneumonia; pneumonia caused by Candida spp or Aspergillus spp. 9.Documented or suspected meningitis, endocarditis, or osteomyelitis. 10.Patients with impaired renal function [Creatinine Clearance (CrCL) 300 mL/min determined according to Cockroft-Gault formula (Appendix 4). 11.Patients with significant liver function abnormalities defined as increase in ALT or AST >3 ULN or in bilirubin >2 ULN or other changes in hematology or clinical biochemistry parameters assessed as clinically relevant by the treating physician noted at study baseline. 12.Patients with known HIV infection with CD4+ cell count < 200/mm3. 13.Patients with any arrhythmia identified at study baseline or having been diagnosed and/or treated in the last 6 months, which is considered clinically relevant by the treating physician. 14.Concomitant morbidity of such severity that the patient is likely to die or present with serious medical conditions within 7 days of study entry. 15.Patients with clinically relevant burns. 16.Patients who are currently enrolled in, or have not yet completed at least 30 days since ending another investigational device or drug trial or are receiving other investigational agent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective -To investigate the pharmacokinetic characteristics of POL7080 co-administered with SoC during 14 days of treatment in VAP patients due to suspected or documented Pseudomonas aeruginosa infection.;Secondary Objective: Secondary Objectives -To investigate POL7080 plus SoC for the following parameters: a.Safety and tolerability b.The efficacy of POL7080 co administered with SoC for the treatment of VAP due to suspected or documented Pseudomonas aeruginosa infection.;Primary end point(s): The pharmacokinetic characteristics of POL7080 co-administered with SoC during 14 days of treatment in VAP patients.;Timepoint(s) of evaluation of this end point: During the 14 days of treatment: On day1 prior to first infusion/dose 1 (as close as possible to the start of infusion), during the infusion at +0.5h, + 1.5h, post-infusion at 5, 30 min and 1, 2, 4, 6 hours, just before the infusions of dose 2, dose 3, dose 4, dose 7, dose 10, dose 13, dose 16, dose 19, during infusion of dose 19 at +0.5h, + 1.5h, dose 19 post infusion at 5, 30 min and 1, 2, 4, 6 hours, before the infusions of dose 20, dose 21, dose 22, dose 25, dose 28, dose 31 dose 34, dose 37 and dose 40. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and tolerability of POL7080 co-administered with SoC by evaluating adverse events (AEs,) changes in vital signs, physical examination results, blood chemistry and haematology, and ECG parameters. Exploratory endpoints include assessment of POL7080 plus SoC for: 1.Clinical cure. Clinical cure on day 10, EOT and TOC will be assessed based on changes in fever, oxygenation, WBC, purulence of sputum/respiratory secretions, pulmonary infiltrate and absence of sputum and or respiratory secretions. Clinical cure will be defined as follows: ?Resolution of all clinical signs and symptoms of pneumonia [unless there is an alternative reason (other than pneumonia) for persistence of certain symptoms or residual signs ans symptoms of pneumonia that do not require further antimicrobial treatment] and improvement or lack of progression of all abnormalities on chest radiograph and no further antipseudomonal antimicrobial therapy for VAP was necessary after the EOT until TOC. 2.Proportion of patients assessed as treatment failure approximately 72 hours after the start of therapy. Treatment failure is defined as: i.Absence of improvement in PaO2/FiO2 as compared to baseline OR ii.Worsening of pulmonary infiltrates OR iii.Development of septic shock* or multiple organ dysfunction syndrome *Septic shock is defined as persistant low blood pressure (systolic 240 as compared to baseline. 5.Evolution of PCT (Procalcitonin), CRP (C-reactive protein), PSP/reg (Pancreatic stone protein/regenerating protein) or other parameters with respect to baseline. 6.Time to 2-log reduction of Pseudomonas aeruginosa as compared to baseline and microbiological outcome at TOC. 7.Improvement of CPIS and SOFA scores as compared to baseline at approximately 72 hours after the start of therapy, day 6, day 10, EOT and TOC. 8.Number of mechanical ventilator free days until test of cure. 9.All-cause mortality on 28th study day.;Timepoint(s) of evaluation of this end point: Secondar | — |
Countries
Spain
Contacts
Public ContactNúria Bordas
Trial Form Support
Outcome results
None listed