A multicenter, open-label, randomized, active-controlled, parallel group, pivotal study to investigate the efficacy, safety and tolerability, and pharmacokinetics of murepavadin combined with one anti-pseudomonal antibiotic versus two anti-pseudomonal antibiotics in adult subjects with ventilator-associated bacterial pneumonia suspected or confirmed to be due to Pseudomonas aeruginosa.

Polyphor Ltd.0 个研究点目标入组 150 人开始时间: 2018年1月10日最近更新: 2019年11月25日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方
入组人数: 150

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

入选标准

•1. Provide written informed consent prior to any study-related procedure not part of normal medical care. Surrogate consent/use of a legally-authorized representative may be provided, if permitted by local country and institution-specific guidelines. If a subject regains consciousness while still in the study and, per the investigator's judgment, the subject is able to read, assess, understand, and make his/her own decision to participate in the trial, the subject can agree to continue study participation and the subject should be re consented, if required by local country and institution-specific guidelines
•2. Male or female subjects, =18 years of age
•3. Hospitalized for = 48 hours, intubated (via endo- or nasotracheal
•tube, including tracheostomy subjects) and receiving mechanical
•ventilation for = 48 hours at the time of randomization, and with acute changes made in the ventilator support system to enhance oxygenation
•4. Chest radiograph shows the presence of new or progressive
•infiltrate(s) characteristic of bacterial pneumonia (based on Investigator's evaluation). A chest computerized tomography (CT) scan may be used in place of a chest X-ray.
•5. Clinical findings to support diagnosis of VABP. At least one of the
•following must be present within 24 hours prior to randomization:
•Documented fever (oral = 38.0°C [100.4°F] or a tympanic, temporal,
•rectal or core temperature = 38.3°C [101°F]), or an axillary or forehead scanner = 37.5°C [99.5°F] OR
•Hypothermia (rectal / core body temperature = 35°C [95.2°F]), OR
•Total peripheral white blood cell count (WBC) = 10,000 cells/mm3, OR
•Leukopenia with WBC = 4500 cells/mm3
•6. Acute Physiology and Chronic Health Evaluation (APACHE II) score
•between 8 and 30 inclusive, within 24 hours prior to randomization
•7. Strong clinical suspicion that the pneumonia is due to P. aeruginosa. Such evidence could be the following criteria, but is not limited to:
•A surveillance culture from a respiratory sample positive for P. aeruginosa.
•A Gram stain performed within 36 hours prior to randomization using an acceptable respiratory sample (protected brush specimen [PBS], BAL,mini-BAL, ETA), showing Gram-negative rods (with or without Grampositive bacteria).
•History of P. aeruginosa infection or colonization of a respiratory
•sample within the last 12 months
•A rapid diagnostic test (RDT), performed within 36 hours prior to
•randomization on respiratory secretions, may further support the
•suspicion based on the above clinical criteria
•At least one risk factor, including the following but not limited to:
•o Broad-spectrum antibiotics (carbapenems, broad-spectrum
•cephalosporins, aminoglycosides, fluoroquinolones) administered
•within 90 days prior to randomization
•o Current hospitalization of = 5 days
•o Late onset (> 4 days after intubation) of VABP
•o History of chronic obstructive pulmonary disease
•o Immunosuppressive disease / therapy (e.g.,steroid use)

排除标准

•1. Known or suspected community-acquired bacterial, viral, fungal
•or parasitic pneumonia
•2. Any of the following health conditions:
•Confirmed legionella infection (Legionella pneumophila
•pneumonia), Aspergillus spp. pneumonia (testing is not required)
•Cystic fibrosis
•Known or suspected Pneumocystis jiroveci pneumonia
•Known or suspected active tuberculosis
•Lung abscess
•Solid organ transplant within 6 months prior to randomization
•Pleural empyema
•3. Bronchial obstruction or a history of post-obstructive pneumonia (this does not exclude subjects with pneumonia who have an underlying chronic obstructive pulmonary disease)
•4. Expected survival < 72 hours
•5. Current or anticipated neutropenia with absolute neutrophil count
•(ANC) < 500 cells/mm3
•6. Severe renal disease defined as an eGFR-MDRD-6 < 30 mL/min/1.73m2, or requirement for peritoneal dialysis, hemodialysis, hemofiltration, or a urine output < 20 mL/hour over a 24-hour period.
•7. Alanine aminotransferase (ALT) or aspartate aminotransferase
•(AST)= 5 times upper limit of normal or Child-Pugh B and C in subjects with chronic liver function impairment
•8. Received systemic or inhaled antibiotic therapy potentially effective against P. aeruginosa within 72 hours prior to randomization as follows:
•- > 8 i.v. doses of an antibiotic administered q.i.d. (e.g.,
•piperacillintazobactam)
•- > 6 i.v. doses of an antibiotic administered t.i.d. (e.g., meropenem)EXCEPTIONS:
•Progression of disease on the prior antibacterial regimen for this
•episode of pneumonia after > 72 hours of treatment OR
•Subject developed symptoms of pneumonia and a new infiltrate while receiving the prior antibacterial regimen for reasons other than the current pneumonia; if the pneumonia occurred while the subject was receiving antibiotics as prophylaxis or for treatment of an unrelated infection, the antibacterial therapy will be considered ineffective irrespective of the susceptibility profile of the study qualifying pathogen,
•Subject received systemic antibacterial therapy that does not cover P. aeruginosa, OR
•Prior therapy with a non-absorbed antibiotic therapy used for gut
•decontamination or to eradicate Clostridium difficile.
•9. Investigator's opinion of clinically significant ECG finding with
•immediate potential for a fatal outcome such as ischemia, infarct, or
•ventricular arrhythmia , or, prior to the current infection, a history of
•New York Heart Association (NYHA) (Appendix X) Class IV cardiac
•10. Stroke (ischemic or intracerebral hemorrhage) within 5 days prior to randomization and increased risk of fatal brain edema as indicated by a major early computerized tomography hypodensity exceeding 50% of the middle cerebral artery territory
•11. Women who are pregnant or nursing, or who are of childbearing
•potential and unwilling to use an acceptable method of birth control as described in the protocol and for a

研究者

发起方

Polyphor Ltd.

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