Study to Compare Lefamulin to Moxifloxacin (With or Without Linezolid) for the Treatment of Adults With Pneumonia
- Conditions
- Community Acquired Pneumonia
- Interventions
- Registration Number
- NCT02559310
- Lead Sponsor
- Nabriva Therapeutics AG
- Brief Summary
This study evaluates the safety and efficacy of lefamulin, a pleuromutilin, for the treatment of adults with moderate to severe community-acquired bacterial pneumonia.
- Detailed Description
Lefamulin is a potent, semi-synthetic antibacterial belonging to a novel class known as the pleuromutilins. Both the intravenous (IV) and oral dosage forms of lefamulin are under investigation in this study. Lefamulin's in vitro antibacterial profile includes the most important bacterial pathogens causing respiratory tract infection (RTI). The antibacterial spectrum comprises S. pneumoniae, H. influenzae, M. catarrhalis, the atypical respiratory pathogens L. pneumophila, C. pneumoniae, and M. pneumoniae, S. aureus including MRSA and CA-MRSA, ß-haemolytic streptococci including S. pyogenes and S. agalactiae, and Enterococcus faecium including vancomycin-resistant enterococci (VRE). Moreover, as demonstrated in cross-resistance studies, lefamulin remains active against clinical isolates resistant to the following antimicrobial(s) (classes): macrolides, lincosamides, streptogramin B, oxazolidinones, tetracyclines, ß lactams, quinolones, trimethoprim-sulfametoxazole, mupirocin, and vancomycin.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 551
-
Be male or female at least 18 years of age.
-
Provide written informed consent and be willing and able to adhere to the study-specified procedures and restrictions.
-
Have an acute illness (7 days duration) with at least 3 of the following symptoms consistent with a lower respiratory tract infection (new or worsening):
- Dyspnea
- New or increased cough
- Purulent sputum production
- Chest pain due to pneumonia
-
Have at least 2 of the following vital sign abnormalities:
- Fever (body temperature >38.0°C (100.4°F) measured orally or equivalent temperature from an alternate body site) or hypothermia (body temperature <35.0°C (95.0°F) measured orally or equivalent temperature from an alternate body site)
- Hypotension (systolic blood pressure <90 mmHg)
- Tachycardia (heart rate >100 beats/min)
- Tachypnea (respiratory rate >20 breaths/min)
-
Have at least 1 other clinical sign or laboratory finding of CABP:
- Hypoxemia (i.e., O2 saturation <90% on room air or while receiving supplemental oxygen at subject's baseline requirement or PaO2 <60 mmHg)
- Auscultatory and/or percussion findings consistent with pneumonia (e.g., crackles, egophony, dullness)
- White blood cell (WBC) count >10,000 cells/mm3 or <4500 cells/mm3 or >15% immature neutrophils (bands) regardless of total WBC count
-
Have radiographically-documented pneumonia within 48 hours before enrollment (i.e., infiltrates in a lobar or multilobar distribution or diffuse opacities on chest x-ray or chest computed tomography scan consistent with acute bacterial pneumonia).
-
Have a Pneumonia Outcomes Research Team (PORT) Risk Class ≥III.
- Have received more than a single dose of a short-acting oral or IV antibacterial for CABP within 72 hours before randomization
- Require concomitant systemic antibacterial therapy potentially effective against CABP pathogens
- Have been hospitalized for 2 or more days within 90 days prior to the onset of symptoms or have resided in a nursing home or long-term healthcare facility within 30 days prior to the onset of symptoms. NOTE: Residence in an independent living facility is permitted.
- Have confirmed or suspected CABP caused by a pathogen known to be resistant to any of the study drugs (e.g., Pseudomonas aeruginosa, any pathogen of the Enterobacteriaceae Family) or attributable to etiologies other than community acquired bacterial pathogens (e.g., ventilator associated pneumonia, hospital acquired bacterial pneumonia, bacterial aspiration pneumonia, Pneumocystis jiroveci pneumonia or other fungal pneumonia, viral or mycobacterial infection of the lung).
- Have a noninfectious cause of pulmonary infiltrates (e.g., pulmonary embolism, chemical pneumonitis from aspiration, hypersensitivity pneumonia, congestive heart failure, bronchial obstruction, lung cancer, cystic fibrosis).
- Have confirmed or suspected pleural empyema (does not include sterile parapneumonic effusions).
- Require mechanical ventilation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lefamulin lefamulin Intravenous lefamulin with potential step-down to oral lefamulin Moxifloxacin +/- Linezolid Linezolid Intravenous moxifloxacin with potential step-down to oral moxifloxacin +/- linezolid Moxifloxacin +/- Linezolid Moxifloxacin Intravenous moxifloxacin with potential step-down to oral moxifloxacin +/- linezolid
- Primary Outcome Measures
Name Time Method Early Clinical Response (ECR) ECR was assessed 96 +/- 24 hours after the first dose of study drug. ECR was defined as survival with improvement in at least 2 signs and symptoms of CABP (relative to baseline), no worsening of any CABP sign or symptom, and no use of concomitant antibiotics (other than adjunctive linezolid, as allowed by the study protocol) for the treatment of CABP through the ECR assessment.
- Secondary Outcome Measures
Name Time Method Investigator's Assessment of Clinical Response (IACR) IACR was assessed at the Test of Cure visit, 5 - 10 days after the last dose of study drug. IACR was defined as resolution or improvement of a subject's clinical signs and symptoms such that no additional antibacterial therapy was administered for the treatment of the current episode of CABP.
Trial Locations
- Locations (99)
Site 3005
🇦🇷La Plata, Buenos Aires, Argentina
Site 3007
🇦🇷Córdoba, Argentina
Site 3001
🇦🇷Córdoba, Argentina
Site 4004
🇧🇦Zenica, Bosnia and Herzegovina
Site 3102
🇧🇷Passo Fundo, Rio Grande Do Sol, Brazil
Site 3103
🇧🇷Campinas, Sao Paulo, Brazil
Site 4112
🇧🇬Pernik, Bulgaria
Site 4103
🇧🇬Ruse, Bulgaria
Site 4108
🇧🇬Smolyan, Bulgaria
Site 4101
🇧🇬Sofia, Bulgaria
Site 4308
🇭🇺Miskolc, Hungary
Site 4403
🇱🇻Daugavpils, Latvia
Site 4110
🇧🇬Sofia, Bulgaria
Site 4204
🇬🇪Tbilisi, Georgia
Site 4111
🇧🇬Sofia, Bulgaria
Site 4205
🇬🇪Tbilisi, Georgia
Site 4202
🇬🇪Tbilisi, Georgia
Site 3204
🇵🇪Lima, Peru
Site 2005
🇵🇭Iloilo City, Philippines
Site 4811
🇷🇴Cluj-Napoca, Romania
Site 4807
🇷🇴Timisoara, Romania
Site 4902
🇷🇺Novosibirsk, Russian Federation
Site 4906
🇷🇺Smolensk, Russian Federation
Site 4809
🇷🇴Timisoara, Romania
Site 4903
🇷🇺St. Petersburg, Russian Federation
Site 4901
🇷🇺St. Petersburg, Russian Federation
Site 5003
🇷🇸Nis, Nišavski Okrug, Serbia
Site 2103
🇹🇭Nonthaburi, Thailand
Site 5203
🇺🇦Chernivtsi, Chernivets'ka Oblast, Ukraine
Site 5211
🇺🇦Odesa, Odes'ka Oblast, Ukraine
Site 5209
🇺🇦Kherson, Khersons'ka Oblast, Ukraine
Site 5207
🇺🇦Kyïv, Ukraine
Site 5208
🇺🇦Sumy, Ukraine
Site 5206
🇺🇦Zhytomyr, Ukraine
Site 1008
🇺🇸Shreveport, Louisiana, United States
Site 1001
🇺🇸Butte, Montana, United States
Site 1005
🇺🇸Minneapolis, Minnesota, United States
Site 1006
🇺🇸Hazard, Kentucky, United States
Site 1009
🇺🇸Akron, Ohio, United States
Site 1004
🇺🇸Splendora, Texas, United States
Site 4106
🇧🇬Sofia, Bulgaria
Site 1002
🇺🇸Dayton, Ohio, United States
Site 3006
🇦🇷Rosario, Santa Fe, Argentina
Site 4303
🇭🇺Törökbálint, Hungary
Site 3004
🇦🇷Cordoba, Argentina
Site 3003
🇦🇷Córdoba, Argentina
Site 4003
🇧🇦Mostar, Bosnia and Herzegovina
Site 4001
🇧🇦Tuzla, Bosnia and Herzegovina
Site 4105
🇧🇬Gabrovo, Bulgaria
Site 4102
🇧🇬Sofia, Bulgaria
Site 4104
🇧🇬Veliko Tarnovo, Bulgaria
Site 4109
🇧🇬Vidin, Bulgaria
Site 4206
🇬🇪Tbilisi, Georgia
Site 4201
🇬🇪Tbilisi, Georgia
Site 4306
🇭🇺Csorna, Hungary
Site 4305
🇭🇺Budapest, Hungary
Site 4307
🇭🇺Miskolc, Hungary
Site 4304
🇭🇺Debrecen, Hungary
Site 4302
🇭🇺Farkasgyepű, Hungary
Site 4401
🇱🇻Liepaja, Latvia
Site 4402
🇱🇻Riga, Latvia
Site 4603
🇳🇱Almelo, Overijssel, Netherlands
Site 4602
🇳🇱Helmond, Netherlands
Site 3205
🇵🇪Trujillo, La Libertad, Peru
Site 3202
🇵🇪Lima, Peru
Site 3201
🇵🇪Lima, Peru
Site 2004
🇵🇭Manila, Philippines
Site 2002
🇵🇭Quezon City, Philippines
Site 2001
🇵🇭Quezon City, Philippines
Site 4703
🇵🇱Skierniewice, Lódzkie, Poland
Site 4704
🇵🇱Warszawa, Mazowieckie, Poland
Site 4701
🇵🇱Lódz, Poland
Site 4702
🇵🇱Wilkowice, Poland
Site 4801
🇷🇴Bucharest, Romania
Site 4802
🇷🇴Palazu Mare, Constanta, Romania
Site 4806
🇷🇴Bucharest, Romania
Site 4810
🇷🇴Bucuresti, Romania
Site 4803
🇷🇴Craiova, Romania
Site 4808
🇷🇴Craiova, Romania
Site 4904
🇷🇺Chelyabinsk, Russian Federation
Site 4905
🇷🇺Yaroslavl, Russian Federation
Site 5002
🇷🇸Belgrade, Serbia
Site 5004
🇷🇸Sremska Kamenica, Serbia
Site 5001
🇷🇸Kragujevac, Šumadijski Okrug, Serbia
Site 5103
🇿🇦Benoni, Gauteng, South Africa
Site 5101
🇿🇦Middelburg, Mpumalanga, South Africa
Site 5105
🇿🇦Thabazimbi, Limpopo, South Africa
Site 5201
🇺🇦Kharkiv, Kharkivs'ka Oblast, Ukraine
Site 5104
🇿🇦Pretoria, Gauteng, South Africa
Site 5204
🇺🇦Ivano-Frankivsk, Ivano-Frankivs'ka Oblast, Ukraine
Site 5102
🇿🇦Krugersdorp, South Africa
Site 5210
🇺🇦Zaporizhzhia, Zaporiz'ka Oblast, Ukraine
Site 5202
🇺🇦Kyiv, Ukraine
Site 5205
🇺🇦Kyiv, Ukraine
Site 5212
🇺🇦Zaporizhzhia, Ukraine
Site 3104
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Site 4107
🇧🇬Lovech, Bulgaria
Site 3101
🇧🇷Sao Paulo Do Rio Preto, Sao Paulo, Brazil
Site 2003
🇵🇭Manila City, Philippines