ventilator-associated bacterial pneumonia MedDRA version: 21.1 Level: LLT Classification code 10081414 Term: Ventilator associated bacterial pneumonia System Organ Class: 100000004862
Conditions
Interventions
Product Name: BV100
Product Code: BV100
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rifabutin
CAS Number: 72559-06-9
Current Sponsor code: BV100
Other descriptive n
Sponsors
BioVersys SAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients who meet all the following diagnostic and clinical criteria are eligible for the study: 1. Provide written informed consent prior to any study-related procedures 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 patient regains consciousness while in the trial and, per the Investigator’s judgment, the patient is able to read, assess, understand, and make his/her own decision to participate in the trial, the patient can agree to continue participation and the patient should be re-consented, if required by local country and institution-specific guidelines. 2. Male or female patients = 18 and < 80 years of age at the time of Informed Consent Form (ICF) signing with a BMI of < 40 kg/m2 at the time of ICF signing. 3. Hospitalized for = 48 hours, intubated (via endo- or nasotracheal tube, including tracheostomy patients) 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, as determined by arterial blood gas (ABG), or worsening PaO2/FiO2 ratio. 4. All patients must have a chest radiograph or a lung CT scan within 48 hours prior to randomization showing the presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia (based on Investigator’s evaluation). 5. Clinical findings to support diagnosis of VABP. At least 1 of the following must be documented to 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 [101.0° F], axillary or forehead scanner = 37.5° C [99.5° F]) OR • Hypothermia (rectal/core body temperature = 35.0° C [95.2° F]), OR • Leukocytosis with total peripheral WBC count = 10 000 cells/mm3, OR • Leukopenia with total peripheral WBC count = 4500 cells/mm3. 6. APACHE II score between 8 and 30, inclusive, within 24 hours prior to randomization. Any data collected before ICF signature as part of a routine standard for patient care (e.g., laboratory values, Glasgow Coma Score [GCS], Acute Physiology Score [APS]) can be used for Screening Visit assessment, if applicable, without repeating the assessments. 7. High probability of pneumonia due to A. baumannii, defined as follows: • RDT, performed within 36 hours prior to randomization, using an acceptable respiratory sample (PBS, BAL, mini-BAL, or ETA) positive for A. baumannii, OR • A surveillance culture from a respiratory sample positive for A. baumannii within 72 hours prior to randomization. Note: The microbiological work-up of the RDT may: • Occur prior to informed consent to participation in the study (only if the RDT was performed as part of a routine standard for patient care, see SoA footnote 6 in Section 2). • Be undertaken on-site • Use a diagnostic test: -routinely performed locally for the detection of A. baumannii from microbiological sample or - provided to the laboratory for the purpose of this study, if the test has regulatory approval in the country where the test is being performed Only if the above methods cannot be used, enrollment can be based on: • A Gram stain performed within 36 hours prior to randomization using an acceptable respiratory sample (PBS, BAL, mini-BAL, or ETA) showing gram-negative cocci (with or without gram-positive bacteria). The Gram stain will be performed in all patient
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria are not eligible to participate in this study: 1. Known or suspected community-acquired bacterial pneumonia or viral, fungal, or parasitic pneumonia. 2. Sustained shock with persisting hypotension requiring vasopressors to maintain mean arterial pressure = 60 mmHg. 3. Known or suspected allergy to polymyxin, rifabutin, BAT, or their excipients. 4. Any of the following health conditions: • Confirmed legionella infection (Legionella pneumophila pneumonia), Aspergillus spp. pneumonia (testing is not required) • Candida spp. infection requiring systemic treatment • 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 • Evidence of deep-seated infection outside the respiratory tract, e.g., endocarditis, osteomyelitis • Known or suspected neuropathy or neuromuscular disease • Known HIV infection 5. Bronchial obstruction or a history of post-obstructive pneumonia (this does not exclude patients with pneumonia who have an underlying chronic obstructive pulmonary disease). 6. Acute graft-versus-host disease Grade = 3. 7. Expected survival 40% of total body surface area. 9. Current or anticipated neutropenia with absolute neutrophil count 6 IV doses of an antibiotic administered qid (e.g., piperacillin-tazobactam) • > 4 IV doses of an antibiotic administered tid (e.g., meropenem) • > 3 IV doses of an antibiotic administered bid (e.g., tigecycline) EXCEPTIONS TO ITEM 12: • Patient developed symptoms of VABP and a new infiltrate while receiving the prior antibacterial regimen for reasons other than the current pneumonia; if the pneumonia occurred while the patient 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 • Patient received systemic antibacterial therapy that does not cover A. baumannii, OR • Prior therapy with a non-absorbable enteral therapy (e.g., oral vancomycin or fidaxomicin) used for gut decontamination or to eradicate C. difficile. 13. Investigator’s opinion of clinically significant ECG finding such as new ischemic changes, infarct, or ventricular arrhythmia with immediate potential for a fatal outcome, bradycardia not corrected by pacemaker or medication, or, prior to the current infection, a history of NYHA Class IV cardiac failure defined as severe limitations – experiences symptom
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the PK properties of BV100 co-administered with Polymyxin B during 7 to 14 days of treatment in patients with ventilator-associated bacterial pneumonia (VABP) due to suspected or documented CRAB infection;Secondary Objective: These secondary objectives are to investigate BV100 plus Polymyxin B compared to BAT for the following parameters: -To assess safety and tolerability -To assess the ACM rates 14 and 28 days after randomization -To determine the clinical cure status at the End of Treatment (EoT) and Test of Cure (ToC) Visits;Primary end point(s): PK properties of rifabutin, 25-OH-deacetyl-rifabutin, and DMI in plasma, including Cmax, tmax and area under the concentration-time curve from dosing (time 0) to time t (AUC0-t);Timepoint(s) of evaluation of this end point: PK sampling is on D-1, D1, D2, D4, D5 and D9 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety will be evaluated in the Safety Population through the assessment of adverse events (AEs), vital signs (blood pressure, heart rate, respiratory rate, body temperature, and pulse oximetry), clinical laboratory evaluations (clinical chemistry, hematology, coagulation, and urinalysis), concomitant medications, renal function, and electrocardiograms (ECGs). -ACM rates 14 and 28 days after randomization in the ITT, micro-MITT, micro-CRMITT, and PP Populations -Clinical cure status determined by the Investigator will be summarized by treatment group at EoT and ToC visits in the ITT, micro-MITT, micro-CRMITT, and PP Populations. Exploratory Endpoints • Change from baseline in PaO2/FiO2 ratio (Days 3, 5, 7, 10, EoT, ToC) in the ITT, Microbiological Intention-to-Treat (micro-ITT), micro-CRMITT, and PP Populations • Assessment of clinical response at Days 3, 5, 7, 10 (if still on study drugs), EoT, and ToC in the ITT, micro-MITT, micro-CRMITT, and PP Populations • Change from baseline in the modified CPIS and SOFA scores (Days 3, 5, 7, 10, EoT, ToC) in the ITT, micro-ITT, micro-CRMITT, and PP Populations • Length of ICU and hospital stay (up to Day 28 and up to ICU/hospital discharge) in the ITT, micro-ITT, micro-CRMITT, and PP Populations • Number of ventilator-free days up to 28 days after randomization in the ITT, micro-ITT, micro-CRMITT, and PP Populations • PK properties of Polymyxin B in plasma including Cmax, tmax, and AUC0-t;Timepoint(s) of evaluation of this end point: 14 and 28 days after randomization End of Treatment (EoT) and Test of Cure (ToC) Visits safety (AEs) will be assessed throughout the study, from D1-D28 | — |
Countries
Georgia, Greece, Hungary
Contacts
Public ContactLead Project Manager
PSI CRO Hungary LLc
Outcome results
None listed