A STUDY TO INVESTIGATE THE EFFICACY, SAFETY TOLERABILITY, ANDPHARMACOKINETICS OF TREATMENT WITH THE DRUG MUREPAVADIN GIVEN WITH ERTAPENEM VERSUS AN ANTI-PSEUDOMONAL-β LACTAM-BASED ANTIBIOTIC IN ADULT SUBJECTS WITH NOSOCOMIAL PNEUMONIA (HOSPITAL-ACQUIRED PNEUMONIA (HAP) OR NOSOCOMIAL PNEUMONIA REFERS TO ANY PNEUMONIA CONTRACTED BY A PATIENT IN A HOSPITAL AT LEAST 48–72 HOURS AFTER BEING ADMITTED) SUSPECTED OR CONFIRMED TO BE DUE TO PSEUDOMONAS AERUGINOSA.
- Conditions
- -J151 Pneumonia due to PseudomonasPneumonia due to PseudomonasJ151
- Registration Number
- PER-054-18
- Lead Sponsor
- Polyphor, Ltd.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 0
Criterios Inclusion claves (Ingles)
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.
2. Male or female subjects, ≥ 18 years of age
Women of childbearing potential are eligible only if the following applies:Negative serum pregnancy test at baseline
Agreement to undertake an urine pregnancy test at the End of Study Visit (30-33 days after last dose)
Agreement to use one of the methods of birth control described in the protocol from screening up to at least 30 days after study treatment discontinuation
Non-vasectomized men are eligible only if they are willing to use a condom during study treatment and for at least 7 days after the last dose.
3. Subjects hospitalized for ≥ 48 hours or those with prior hospital admission of ≥ 48 hours if they were discharged within the last 7 days
4. Intubated (via naso- or endotracheal tube, including tracheostomy subjects) and receiving mechanical ventilation for ≥ 48 hours, and acute changes made in the ventilator support to maintain adequate PaO2 or SpO2
OR
At least 2 of the following signs or symptoms presenting within 24 hours prior to randomization:
-New onset of cough or worsening of baseline cough
-Auscultatory findings on pulmonary examination of rales and/or evidence of pulmonary consolidation (e.g., dullness on percussion, bronchial breath sounds, or egophony)
-Dyspnea, tachypnea (respiratory rate > 25/minute), particularly if any or all of these signs or symptoms are progressive in nature
-Hypoxemia (e.g., a partial pressure of oxygen [PaO2] < 60 mm Hg while the subject is breathing on room air as determined by arterial blood gas (ABG) or oxygen saturation [SpO2] < 90% while the subject is breathing on room air as determined by pulse oximetry, or increased ventilator demand if on mechanical ventilation for < 48 hours prior to randomization
-New onset of sputum or suctioned respiratory secretions characterized by purulent appearance indicative of bacterial infection or a worsening in character of purulent appearance
5. Chest radiograph shows the presence of new or progressive infiltrate(s) characteristic of bacterial pneumonia (based on Investigator’s evaluation). A chest computed tomography (CT) scan may be used in place of a chest x-ray
6. At least 1 of the following 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
-Total peripheral white blood cell count (WBC) ≥ 10,000 cells/mm3, OR
-Leucopenia with WBC ≤ 4,500 cells/mm3
7. Acute Physiology and Chronic Health Evaluation
(APACHE II) score between 8 and 25, inclusive, within 24 hours prior to randomization
8. Strong clinical suspicion of pneumonia 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]
Criterios de Exclusion claves (Ingles)
1. Known or suspected community-acquired, 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 jirovecii 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
4. Expected survival < 72 hours
5. Burns > 40 % of total body surface area
6. Current or anticipate neutropenia with absolute neutrophil count < 500 cells/mm3
7. Severe renal disease defined as the estimated glomerular filtration rate per the 6-point Modification of Diet in Renal Disease (eGFR-MDRD-6 < 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.
8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 5-times upper limit of normal or Child-Pugh B and C in subjects with chronic hepatic function impairment
9. Received systemic or inhaled anti-pseudomonal antibiotic therapy within 72 hours prior to randomization as follows:
-> 5 i.v. doses of an antibiotic administered q.i.d.(e.g., piperacillin-tazobactam)
-> 4 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, provided prior respiratory or blood culture did not grow an anti-pseudomonal
β-lactam-resistant P. aeruginosa pathogen, or only a Gram-positive pathogen. Requires microbiological confirmation of a Gram-negative pathogen, 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 ofthe 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.
10. Investigator’s opinion of clinically significant electrocardiogram (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) Class IV cardiac failure
11. Stroke (ischemic or intracerebral hemorrhage) within 5 days prior to randomization and there is an increased risk of fatal brain edema as indicated by a major early computerized tomography hypodensity exceeding 50%of the middle cerebral artery territory
12. Women who are pregnant or nursing
13. Persisting hypotension requiring sympathomimetic agents (> 0.2 µg/kg/min norepinephrine or a total of all vasopressors > 0.2 µg/kg/min norepinephrine equivalents) to maintain a MAP ≥ 65 mmHg despite adequate fluid administration. See Appendix XI for norepinephrine equivalency table.
14. Evidence of co-infection with ertapenem
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method