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A study of BV100 plus low dose polymyxin B for treating hospital -acquired and ventilator-associated pneumonia caused by antibiotic resistant Acinetobacter bacteria
EU CTIS ID: 2025-524092-23-00
What this study is testing
To compare the efficacy of BV100 plus low dose polymyxin B with colistin plus high dose ampicillin/sulbactam in patients with CRABC infections in Part A
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- (1) Provide written informed consent prior to any study related procedures not part of normal medical care. If permitted by local country and institution-specific guidelines, surrogate consent/use of a legally authorized representative may be provided. Alternatively, the decision can be made according to the procedure permitted by local law and institutional Standard Operating Procedures. If a patient regains consciousness while in the study and, per the Investigator’s judgment, the patient is able to read, assess, understand, and make his/her own decision to participate in the study, the patient may agree to continue participation. In such cases, the patient must be reconsented.
- (2) Male or female patients, ≥ 18 and ≤ 82 years of age at the time of signing informed consent.
- (3) A confirmed diagnosis of HABP or VABP requiring treatment with IV antibiotics in the judgment of the Investigator.
- (4) High probability of a pneumonia (HABP or VABP) due to ABC as a single pathogen, or member of a polymicrobial infection based on evidence from RDT from a sample collected within a specified time period as per the protocol (CCI) prior to randomization, AND one of the following: (a) Has received no more than a specified number of hours as per the protocol (CCI) of potentially active antimicrobial treatment against CRABC prior to the first dose of study drug; OR (b) Is clinically failing prior treatment regimens (i.e., clinical deterioration or failure to improve after at least 48 hours of antibiotic treatment). Note: RDTs using an acceptable respiratory sample (PSB, BAL, mini BAL, ETA, or sputum) should be used to enable early detection of possible ABC pneumonia. A minimum amount in copies/mL (CCI) of ABC are required to consider RDT as positive. Patients can be randomized based on the results of the RDT while awaiting results of cultures from the local laboratory. However, if the respiratory sample does not grow ABC in the local microbiology laboratory culture, these patients will be withdrawn from the study drug treatment and treated at the Investigator’s discretion. Patients randomized in Part A based on positive RDT but subsequently with values below thresholds for ABC for the resulting quantitative or semi quantitative cultures can continue the study treatment at the discretion of the Investigator. Refer to the Microbiology Laboratory Manual for specifics.
- (5) An Acute Physiology and Chronic Health Evaluation II (APACHE II) < 30 or quick Sequential Organ Failure Assessment (qSOFA) score ≥ 2 at Screening. Note: an APACHE II score or a qSOFA score that was calculated as part of standard of care within 24 hours of Screening may be used and does not need to be repeated.
- (6) Women of childbearing potential (i.e., not post-menopausal or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test before randomization. Participating women of childbearing potential must be willing to consistently use one highly effective method of contraception (e.g., condom, combined oral contraceptive, implant, injectable, indwelling intrauterine device, or a vasectomized partner) from Screening until at least 30 days after administration of the last dose of study drug. Note: Women of childbearing potential who are on combined oral contraceptives only are required to use an additional (i.e. barrier) method of contraception from Screening until at least 30 days after administration of the last dose of study drug.
You likely can't join if
- (1) For Part A only, patients with an infection known to be resistant to colistin (defined as MIC ≥ 4 mg/L by a non-agar-based method), with a known intolerance to polymyxins, or taking any drug that prevents them from receiving polymyxins.
- (18) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3× the upper limit of normal (ULN) AND total bilirubin > 2×ULN at Screening (using local laboratory values); or Child Pugh Class C in patients with chronic liver function impairment. Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis, hepatic cirrhosis, hepatic failure, chronic ascites, or hepatic encephalopathy. Note: Patients with AST or ALT up to 5×ULN are eligible if these elevations are acute and are documented as being directly related to the infectious process being treated.
- (19) 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 New York Heart Association Class IV cardiac failure defined as severe limitations – experiences symptoms even while at rest, mostly bedbound patients, within 1 year.
- (8) Inability to provide proper respiratory specimens for culture. Respiratory samples from ETA or expectorated or induced sputum should show ≤ 10 squamous epithelial cells and ≥ 25 polymorphonuclear neutrophils per 100× field.
- (20) Abnormal QT interval corrected for heart rate by Fridericia formula (QTcF): > 500 ms confirmed with repeat ECG.
- (21) Stroke (ischemic or intracerebral hemorrhage) within 10 days prior to randomization or expected survival from stroke < 28 days or a Glasgow Coma Scale (GCS) score 3 with no hope of improvement.
See the full eligibility criteria
Who can join
- (1) Provide written informed consent prior to any study related procedures not part of normal medical care. If permitted by local country and institution-specific guidelines, surrogate consent/use of a legally authorized representative may be provided. Alternatively, the decision can be made according to the procedure permitted by local law and institutional Standard Operating Procedures. If a patient regains consciousness while in the study and, per the Investigator’s judgment, the patient is able to read, assess, understand, and make his/her own decision to participate in the study, the patient may agree to continue participation. In such cases, the patient must be reconsented.
- (2) Male or female patients, ≥ 18 and ≤ 82 years of age at the time of signing informed consent.
- (3) A confirmed diagnosis of HABP or VABP requiring treatment with IV antibiotics in the judgment of the Investigator.
- (4) High probability of a pneumonia (HABP or VABP) due to ABC as a single pathogen, or member of a polymicrobial infection based on evidence from RDT from a sample collected within a specified time period as per the protocol (CCI) prior to randomization, AND one of the following: (a) Has received no more than a specified number of hours as per the protocol (CCI) of potentially active antimicrobial treatment against CRABC prior to the first dose of study drug; OR (b) Is clinically failing prior treatment regimens (i.e., clinical deterioration or failure to improve after at least 48 hours of antibiotic treatment). Note: RDTs using an acceptable respiratory sample (PSB, BAL, mini BAL, ETA, or sputum) should be used to enable early detection of possible ABC pneumonia. A minimum amount in copies/mL (CCI) of ABC are required to consider RDT as positive. Patients can be randomized based on the results of the RDT while awaiting results of cultures from the local laboratory. However, if the respiratory sample does not grow ABC in the local microbiology laboratory culture, these patients will be withdrawn from the study drug treatment and treated at the Investigator’s discretion. Patients randomized in Part A based on positive RDT but subsequently with values below thresholds for ABC for the resulting quantitative or semi quantitative cultures can continue the study treatment at the discretion of the Investigator. Refer to the Microbiology Laboratory Manual for specifics.
- (5) An Acute Physiology and Chronic Health Evaluation II (APACHE II) < 30 or quick Sequential Organ Failure Assessment (qSOFA) score ≥ 2 at Screening. Note: an APACHE II score or a qSOFA score that was calculated as part of standard of care within 24 hours of Screening may be used and does not need to be repeated.
- (6) Women of childbearing potential (i.e., not post-menopausal or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test before randomization. Participating women of childbearing potential must be willing to consistently use one highly effective method of contraception (e.g., condom, combined oral contraceptive, implant, injectable, indwelling intrauterine device, or a vasectomized partner) from Screening until at least 30 days after administration of the last dose of study drug. Note: Women of childbearing potential who are on combined oral contraceptives only are required to use an additional (i.e. barrier) method of contraception from Screening until at least 30 days after administration of the last dose of study drug.
- (7) Diagnosed with HABP or VABP as defined in detail in the Protocol.
- (8) Part B will include patients with HABP or VABP who do not qualify for Part A. These patients should be considered for enrollment in Part B if they meet ANY of the following criteria, in addition to the general inclusion above: (1) Have an infection caused by CRABC organisms known to be resistant to colistin or polymyxin B (defined as MIC ≥ 4 mg/L by a non-agar-based method). (2) For known colistin- or polymyxin B-resistant infections, the following must be satisfied: (a) Have a known resistant infection based on evidence from culture and susceptibility testing by a non-agar-based method within a specified time period as per the protocol (CCI) prior to randomization, either alone or as a single organism of a polymicrobial infection; AND has received no more than a specified number of hours as per the protocol (CCI) of an antimicrobial agent to which the CRABC is susceptible prior to the first dose of study drug; OR (b) Have documented clinical evidence of failure (i.e., clinical deterioration or failure to improve that is attributable to CRABC) after at least a specified number of hours as per the protocol (CCI) of treatment with colistin or polymyxin B.
What rules you out
- (1) For Part A only, patients with an infection known to be resistant to colistin (defined as MIC ≥ 4 mg/L by a non-agar-based method), with a known intolerance to polymyxins, or taking any drug that prevents them from receiving polymyxins.
- (18) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3× the upper limit of normal (ULN) AND total bilirubin > 2×ULN at Screening (using local laboratory values); or Child Pugh Class C in patients with chronic liver function impairment. Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis, hepatic cirrhosis, hepatic failure, chronic ascites, or hepatic encephalopathy. Note: Patients with AST or ALT up to 5×ULN are eligible if these elevations are acute and are documented as being directly related to the infectious process being treated.
- (19) 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 New York Heart Association Class IV cardiac failure defined as severe limitations – experiences symptoms even while at rest, mostly bedbound patients, within 1 year.
- (8) Inability to provide proper respiratory specimens for culture. Respiratory samples from ETA or expectorated or induced sputum should show ≤ 10 squamous epithelial cells and ≥ 25 polymorphonuclear neutrophils per 100× field.
- (20) Abnormal QT interval corrected for heart rate by Fridericia formula (QTcF): > 500 ms confirmed with repeat ECG.
- (21) Stroke (ischemic or intracerebral hemorrhage) within 10 days prior to randomization or expected survival from stroke < 28 days or a Glasgow Coma Scale (GCS) score 3 with no hope of improvement.
- (22) Women who are pregnant or nursing.
- (23) Patients who are currently enrolled in or have not yet completed, in the last 30 days or 5 half lives, whichever is longer, another investigational device or drug study or those who are receiving other investigational agents.
- (9) Received more than a specified number of hours as per the protocol (CCI) of potentially active treatment against CRABC prior to the first dose of study drug. Examples for exceptions to exclusion criterion (9): (a) Patient developed symptoms of VABP or HABP and/or a new infiltrate or positive blood culture 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 (b) Patient received systemic antibacterial therapy that does not cover CRABC; OR (c) Prior therapy with a nonabsorbed antibiotic therapy (e.g., oral vancomycin, metronidazole, or fidaxomicin) used for gut decontamination or to eradicate Clostridium difficile.
- (12) Requirement for continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or divalproex sodium during the study.
- (10) Known or suspected allergy to polymyxin, rifabutin, colistin, ampicillin/sulbactam, meropenem or their excipients.
- (5) Patients classified under futility of care, as determined by the medical team, indicating a lack of potential for benefit from intervention or patients who are permanent residents of long-term care facilities and have been assessed by the clinical team as receiving palliative or comfort-focused care.
- (11) Acute graft-versus-host disease (Grade ≥ 3).
- (2) Evidence of active concurrent pneumonia requiring additional antimicrobial treatment caused by, e.g., Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, Pneumocystitis jiroveci, Aspergillus spp, respiratory syncytial virus, influenza and parainfluenza viruses, Middle East respiratory syndrome coronavirus, mycobacteria, mucormycosis. Note: If these organisms are identified but it is deemed by the Investigator that no treatment is warranted and their presence does not significantly change the prognosis of the patient, then the patient may be considered for this study.
- (3) Any of the following health conditions: (a) Pulmonary disease that precludes evaluation of a therapeutic response (such as lung cancer resulting in bronchial obstruction or on the same side as the pneumonia, active tuberculosis, cystic fibrosis, granulomatous disease, fungal pulmonary infection, lung abscess, pleural empyema, post obstructive pneumonia, or known or suspected coronavirus disease 2019 infection without clinical improvement). Patients with known or suspected severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) infection are not allowed to be randomized in this study, unless the suspected A. baumannii pneumonia is diagnosed 7 days or more after the detection of SARS CoV 2. However, a patient who was previously polymerase chain reaction (PCR) positive for SARS CoV 2 and remains PCR positive for SARS CoV 2 at least 14 days after the first SARS CoV 2 PCR positive test may be included in the study. (b) Pleural empyema (exception: acceptable if drainage occurs within 24 hours of Screening and patient is expected to be treated in ≤ 14 days). (c) Solid organ transplant within 6 months prior to randomization. (d) Evidence of deep seated infection, e.g., Gram-negative osteomyelitis, or meningitis requiring prolonged therapy. If a deep-seated infection is drained and sanitized, it does not exclude the patient. (e) Acute infective endocarditis due to Gram-positive bacteria that requires urgent treatment/emergent indication of surgery (i.e., heart failure because of valvular insufficiency or septic shock), or patients in whom surgery is contraindicated due to prohibitive risk for surgery due to comorbidities. (f) Surgical wound infections requiring further surgical management e.g., wound closure, drain removal. (g) Peritonitis. (h) Irremovable implantable device or line thought to be the source of the ABC infection. (i) Known or suspected neuropathy or neuromuscular disease. (j) Human immunodeficiency virus infection. (k) Chronic immunosuppression due to drugs and/or underlying disease e.g., severe combined immunodeficiency, lupus, active chemotherapy, azathioprine; at the discretion of the Investigator.
- (4) Bronchial obstruction or a history of post obstructive pneumonia (this does not exclude patients with pneumonia who have an underlying chronic obstructive pulmonary disease).
- (24) Unable or not willing, in the opinion of the Investigator, to comply with all study protocol.
- (6) Sustained shock with persisting hypotension requiring vasopressors to maintain mean arterial pressure ≥ 65 mmHg (calculate mean arterial pressure = diastolic pressure plus 1/3 (systolic pressure minus diastolic pressure)) with patients requiring escalating vasopressor support to maintain adequate arterial pressure in conjunction with rising lactate. Examples for exceptions to exclusion criterion (6): (a) Patients sedated with propofol or requiring heavy sedation for whom their physician prescribed a low nonescalating dose of norepinephrine (< 1 µg/kg/min) to preserve adequate arterial pressure. (b) Patients receiving a weaning dose of noradrenaline < 1 µg/kg/min in the absence of hypotension or septic shock. (c) Patients receiving a low dose of norepinephrine (< 1 µg/kg/min) or equivalent to maintain the blood pressure after a ventilator parameter change.
- (7) Diagnosis of ventilator-associated tracheobronchitis.
- (13) Requirement at the time of randomization for any reason, or likely to require during the patient’s participation in the study (from randomization through the EoS Visit), for additional systemic Gram-negative antimicrobial therapy potentially active toward CRABC.
- (14) Expected survival < 72 hours or a Do Not Resuscitate Order.
- (15) Burns > 40% of total body surface area.
- (16) Presence of neutropenia (absolute neutrophil count < 1500/mm3) obtained from a local laboratory at Screening, or anticipated neutropenia with absolute neutrophil count < 1500 cells/mm3.
- (17) Severe renal disease defined as an estimated glomerular filtration rate (eGFR) as per Modification of Diet in Renal Disease (MDRD) formula (MDRD eGFR) < 30 mL/min/1.73 m2, or requirement for peritoneal dialysis, hemodialysis, hemofiltration, or a urine output < 20 mL/hour over a 24 hour period.
The study team makes the final eligibility decision.
Where it's taking place
- Ukraine
- Bosnia and Herzegovina
- Brazil
- Turkey
- Georgia
- Korea, Republic of
- Mexico
- China
- Serbia
- Philippines
- United States
- Israel
- Peru
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Ukraine; Bosnia and Herzegovina; Brazil; Turkey; Georgia; Korea, Republic of and 7 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.