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Study to Compare Lefamulin to Moxifloxacin (With or Without Linezolid) for the Treatment of Adults With Pneumonia (LEAP)

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ClinicalTrials.gov Identifier: NCT02559310
Recruitment Status : Completed
First Posted : September 24, 2015
Results First Posted : October 23, 2019
Last Update Posted : October 23, 2019
Sponsor:
Information provided by (Responsible Party):
Nabriva Therapeutics AG

Study Description
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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.

Condition or disease Intervention/treatment Phase
Community Acquired Pneumonia Drug: lefamulin Drug: Moxifloxacin Drug: Linezolid Phase 3

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 551 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Lefamulin (BC 3781) Versus Moxifloxacin (With or Without Adjunctive Linezolid) in Adults With Community-Acquired Bacterial Pneumonia
Study Start Date : September 2015
Actual Primary Completion Date : April 2017
Actual Study Completion Date : May 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arms and Interventions
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Arm Intervention/treatment
Experimental: Lefamulin
Intravenous lefamulin with potential step-down to oral lefamulin
 Drug: lefamulin
antibacterial agent
Other Name: BC-3781
Active Comparator: Moxifloxacin +/- Linezolid
Intravenous moxifloxacin with potential step-down to oral moxifloxacin +/- linezolid
 Drug: Moxifloxacin
antibacterial agent
Other Name: Avelox

Drug: Linezolid
antibacterial agent
Other Name: Zyvox


Outcome Measures
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Primary Outcome Measures :
  1. Early Clinical Response (ECR) [ Time Frame: 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 :
  1. Investigator's Assessment of Clinical Response (IACR) [ Time Frame: 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

  2. Investigator's Assessment of Clinical Response (IACR) [ Time Frame: 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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Be male or female at least 18 years of age.
  2. Provide written informed consent and be willing and able to adhere to the study-specified procedures and restrictions.

  3. 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

  4. 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)

  5. 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
  6. 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).
  7. Have a Pneumonia Outcomes Research Team (PORT) Risk Class ≥III.

Exclusion Criteria:

  1. Have received more than a single dose of a short-acting oral or IV antibacterial for CABP within 72 hours before randomization
  2. Require concomitant systemic antibacterial therapy potentially effective against CABP pathogens
  3. 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.
  4. 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).
  5. 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).
  6. Have confirmed or suspected pleural empyema (does not include sterile parapneumonic effusions).
  7. Require mechanical ventilation.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02559310


Locations
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Sponsors and Collaborators
Nabriva Therapeutics AG
Investigators
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Study Chair: Jennifer Schranz, MD Nabriva Therapeutics
  Study Documents (Full-Text)

Documents provided by Nabriva Therapeutics AG:
Statistical Analysis Plan  [PDF] August 30, 2017
Study Protocol  [PDF] March 15, 2016

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Nabriva Therapeutics AG
ClinicalTrials.gov Identifier: NCT02559310    
Other Study ID Numbers: NAB-BC-3781-3101
First Posted: September 24, 2015    Key Record Dates
Results First Posted: October 23, 2019
Last Update Posted: October 23, 2019
Last Verified: October 2019
Keywords provided by Nabriva Therapeutics AG:
Pneumonia
CABP
CAP
Community acquired bacterial pneumonia
Additional relevant MeSH terms:
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Pneumonia
Respiratory Tract Infections
Infections
Lung Diseases
Respiratory Tract Diseases
Moxifloxacin
Linezolid
Lefamulin
 Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Synthesis Inhibitors