A study to investigate the efficacy, safety tolerability, and pharmacokinetics of treatment with the drug murepavadin combined with one anti-pseudomonal antibiotic versus two anti-pseudomonal antibiotics in adult subjects with ventilator-associated bacterial pneumonia (type of lung infection that occurs in people who are on mechanical ventilation breathing machines in hospitals) suspected or confirmed to be due to a bacteria called Pseudomonas aeruginosa.
- Conditions
- Ventilator-associated bacterial pneumonia (VABP)MedDRA version: 20.1 Level: LLT Classification code 10065153 Term: Ventilator associated pneumonia System Organ Class: 100000004862Therapeutic area: Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]
- Registration Number
- EUCTR2017-003933-27-EE
- Lead Sponsor
- Polyphor Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 150
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
AND
• 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)
Are the
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,
OR
• 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
failure
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method