Health Condition 1: J151- Pneumonia due to Pseudomonas
Conditions
Interventions
Intervention1: Experimental Arm - Combine Murepavadin with one authorized anti-pseudomonal agent from either group, preferably with one anti-pseudomonal β-lactam antibiotic.: Combine murepavadin with
Sponsors
Polyphor Ltd
Covance India Pharmaceutical Services Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 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 investigatorâ??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, more than 18 years of age 3. Hospitalized for more than 48 hours, intubated (via endo- or nasotracheal tube, including tracheostomy subjects) and receiving mechanical ventilation for more than 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 Investigatorâ??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 more than 38.0°C [100.4º F] or a tympanic, temporal, rectal or core temperature more than 38.3º°C [101º F]), or an axillary or forehead scanner more than 37.5° C [99.5° F] OR - Hypothermia (rectal / core body temperature less than 35º°C [95.2º F]), OR - Total peripheral white blood cell count (WBC) more than or equal to 10,000 cells/mm3, OR - Leukopenia with WBC 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 (more than equal to 25 PMNs/LPF and less than equal to 10 squamous epithelial cells/LPF), showing Gram-negative rods (with or without Gram-positive bacteria) Note:if BAL, mini-BAL, or PBS is available at the site, these modalities are recommended rather than an ETA for obtaining the baseline lower respiratory tract specimen - History of P. aeruginosa infection or colonization from 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, e.g., o Broad-spectrum antibiotics (carbapenems, broad-spectrum cephalosporins, aminoglycosides, fluoroquinolones) administered within 90 days prior to randomization, o Current hospitalization of more than or equal 5 days, o Late onset (more than 4 days after intubation) of VABP, o History of chronic obstructive pulmonary disease, o Immunosuppressive
Exclusion criteria
Exclusion criteria: Subjects are not eligible for this trial if they fulfill any of the following exclusion criteria: 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 5. Current or anticipated neutropenia with absolute neutrophil count (ANC) 6. Severe renal disease defined as an eGFR-MDRD-6 peritoneal dialysis, hemodialysis, hemofiltration, or a urine output period. 7. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than or equal to 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., piperacillin-tazobactam) - > 6 i.v. doses of an antibiotic administered t.i.d. (e.g., meropenem)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clinical cure:- Complete resolution or marked improvement of all signs and symptoms. - None of the clinical failure criteria (see below) are fulfilled. Clinical failure: - Worsening or no improvement in clinical signs and symptoms, - Treatment-limiting AE leading to discontinuation of study drug antibiotics, when subject requires alternative antimicrobial therapy to treat the pneumonia - Death.Timepoint: Test-of-Cure (ToC) visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| - ACM rates within 14 and 28 days after randomization in different analysis sets - Clinical cure rates at Day 3, 5, 7, 10 (if still on study drugs), the EoT (End-of-Treatment) visit in different analysis sets.Timepoint: ACM rates within 14 and 28 days after randomization and Clinical cure rates at Day 3, 5, 7, 10 | — |
Countries
Brazil, Estonia, France, Greece, Hungary, India, Ireland, Israel, Mexico, Republic of Korea, Romania, South Africa, Spain, Thailand, United States of America
Contacts
Public ContactDr Sanish Davis
Covance India Pharmaceutical Services Pvt. Ltd.
Outcome results
None listed