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Tedizolid Phosphate (TR-701 FA, MK-1986) vs Linezolid for the Treatment of Nosocomial Pneumonia (MK-1986-002)

Primary Purpose

Pneumonia

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Tedizolid phosphate
Linezolid
Sponsored by
Cubist Pharmaceuticals LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pneumonia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Requires IV antibiotic therapy with diagnosis of ventilated nosocomial pneumonia
  • Gram-positive bacteria on respiratory Gram stain

Exclusion Criteria:

  • Pneumonia of community, viral, fungal or parasitic etiology
  • Structural lung abnormalities
  • Immunosuppression
  • Previous antibiotics for > 24 hours
  • Expected survival of < 72 hours

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Tedizolid phosphate IV

    Linezolid IV

    Arm Description

    Ventilated HABP/VABP participants receive tedizolid phosphate 200 mg IV once daily for 7 days, or for 14 days for concurrent bacteremia.

    Ventilated HABP/VABP participants receive linezolid 600 mg IV every 12 hours for 10 days, or for 14 days for concurrent bacteremia.

    Outcomes

    Primary Outcome Measures

    Number of Participants With All-Cause Mortality in the Intent-to-Treat (ITT) Population
    The numbers of participants with all-cause mortality within 28 days after randomization was determined in the ITT population. Any participants who were lost to follow-up and not known to be alive or deceased by Day 28 were imputed as deceased.

    Secondary Outcome Measures

    Number of Participants With All-Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population
    The numbers of participants with all-cause mortality within 28 days after randomization was determined in the mITT population. Any participants who were lost to follow-up and not known to be alive or deceased by Day 28 were imputed as deceased.
    Clinical Response at Test of Cure (TOC) Visit in the Intent-to-Treat (ITT) Population
    The clinical response in the ITT population at the TOC visit (derived from the Investigator's assessment at the EOT and TOC visits) was determined by the investigator to be either: clinical success, clinical failure, or indeterminate. Clinical success was declared when most or all clinical signs were completely resolved, with no new signs of infection, no additional antibiotic therapy was required, and the participant was alive. Indeterminate was declared when the investigator could not determine success or failure. Clinical failure was declared with progression, relapse, or recurrence of new symptoms of infection, or a persistence or insufficient improvement in signs and symptoms of VNP.
    Clinical Response at Test of Cure (TOC) Visit in the Clinically-Evaluable (CE) Population
    The clinical response in the CE population at the TOC visit (derived from the Investigator's assessment at the EOT and TOC visits) was determined by the investigator to be either: clinical success, clinical failure, or indeterminate. Clinical success was declared when most or all clinical signs were completely resolved, with no new signs of infection, no additional antibiotic therapy was required, and the participant was alive. Indeterminate was declared when the investigator could not determine success or failure. Clinical failure was declared with progression, relapse, or recurrence of new symptoms of infection, or a persistence or insufficient improvement in signs and symptoms of VNP.
    Number of Methicillin-Susceptible Staphylococcus Aureus (MSSA)-Infected Participants With All-Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population
    The number of MSSA-infected participants with all-cause mortality within 28 days after randomization was determined in the mITT population. Participants who had confirmed MSSA culture results from respiratory tract or pleural fluid specimens obtained within 36 hours of study Day 1 were included. Any participants who were lost to follow-up and not known to be alive or deceased by Day 28 were imputed as deceased.
    Number of Methicillin-Resistant Staphylococcus Aureus (MRSA)-Infected Participants With All-Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population
    The number of MRSA-infected participants with all-cause mortality within 28 days after randomization was determined in the mITT population. Participants who had confirmed MRSA culture results from respiratory tract or pleural fluid specimens obtained within 72 hours of study Day 1 were included. Any participants who were lost to follow-up and not known to be alive or deceased by Day 28 were imputed as deceased.
    Number of Participants With a Favorable Response at End-of-Therapy (EOT) Visit in the Microbiological Intent-to-Treat (mITT) Population
    The number of patients in the mITT population with a favorable response at EOT was determined. Favorable response included eradication (absence of the baseline pathogen) and presumed eradication (no source specimen to culture in a participant assessed as a clinical cure by the investigator).
    Number of Participants With a Favorable Response at End-of-Therapy (EOT) Visit in the Microbiologically-Evaluable 1 (ME-1) Population
    The number of patients in the ME-1 population with a favorable response at EOT was determined. Favorable response included eradication (absence of the baseline pathogen) and presumed eradication (no source specimen to culture in a participant assessed as a clinical cure by the investigator).
    Number of Participants With a Favorable Response at Test-of-Cure (TOC) Visit in the Microbiological Intent-to-Treat (mITT) Population
    The number of patients in the mITT population with a favorable response at TOC was determined. Favorable response included eradication (absence of the baseline pathogen) and presumed eradication (no source specimen to culture in a participant assessed as a clinical cure by the investigator).
    Number of Participants With a Favorable Response at Test-of-Cure (TOC) Visit in the Microbiologically-Evaluable 2 (ME-2) Population
    The number of patients in the ME-2 population with a favorable response at TOC was determined. Favorable response included eradication (absence of the baseline pathogen) and presumed eradication (no source specimen to culture in a participant assessed as a clinical cure by the investigator).
    Number of Participants With ≥1 Adverse Events (AEs)
    An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Safety analysis is based on actual treatment received instead of randomization.
    Number of Participants Discontinuing Study Therapy Due to an Adverse Event (AE)
    An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Safety analysis was based on actual treatment received and not randomization.

    Full Information

    First Posted
    December 18, 2013
    Last Updated
    June 10, 2019
    Sponsor
    Cubist Pharmaceuticals LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02019420
    Brief Title
    Tedizolid Phosphate (TR-701 FA, MK-1986) vs Linezolid for the Treatment of Nosocomial Pneumonia (MK-1986-002)
    Official Title
    A Phase 3 Randomized Double-blind Study Comparing TR-701 FA and Linezolid in Ventilated Gram-positive Nosocomial Pneumonia
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2019
    Overall Recruitment Status
    Completed
    Study Start Date
    January 6, 2014 (Actual)
    Primary Completion Date
    June 22, 2018 (Actual)
    Study Completion Date
    June 22, 2018 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Cubist Pharmaceuticals LLC

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This is a 1:1 ratio, randomized, double-blind, double-dummy, multicenter, global Phase 3 study of tedizolid phosphate (TR-701 FA) 200 mg intravenous (IV) once daily for 7 days versus linezolid (Zyvox®, Zyvoxid®, etc) 600 mg IV every 12 hours for 10 days for the treatment of ventilated participants with presumed gram-positive hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP), collectively referred to as ventilated nosocomial pneumonia (VNP). Participants with concurrent gram-positive bacteremia are to receive 14 days of active therapy in either treatment arm. The primary objective is to determine the noninferiority (NI) in all-cause mortality (ACM) within 28 days after randomization of IV tedizolid phosphate compared with IV linezolid in the Intent to Treat (ITT) Analysis Set (NI is declared when the lower bound of the 95% CI > -10).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pneumonia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    726 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Tedizolid phosphate IV
    Arm Type
    Experimental
    Arm Description
    Ventilated HABP/VABP participants receive tedizolid phosphate 200 mg IV once daily for 7 days, or for 14 days for concurrent bacteremia.
    Arm Title
    Linezolid IV
    Arm Type
    Active Comparator
    Arm Description
    Ventilated HABP/VABP participants receive linezolid 600 mg IV every 12 hours for 10 days, or for 14 days for concurrent bacteremia.
    Intervention Type
    Drug
    Intervention Name(s)
    Tedizolid phosphate
    Other Intervention Name(s)
    SIVEXTRO®, TR-701 FA, MK-1986
    Intervention Description
    Tedizolid phosphate IV 200 mg once daily
    Intervention Type
    Drug
    Intervention Name(s)
    Linezolid
    Other Intervention Name(s)
    ZYVOX®
    Intervention Description
    Linezolid IV 600 mg twice daily
    Primary Outcome Measure Information:
    Title
    Number of Participants With All-Cause Mortality in the Intent-to-Treat (ITT) Population
    Description
    The numbers of participants with all-cause mortality within 28 days after randomization was determined in the ITT population. Any participants who were lost to follow-up and not known to be alive or deceased by Day 28 were imputed as deceased.
    Time Frame
    Up to 28 days
    Secondary Outcome Measure Information:
    Title
    Number of Participants With All-Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population
    Description
    The numbers of participants with all-cause mortality within 28 days after randomization was determined in the mITT population. Any participants who were lost to follow-up and not known to be alive or deceased by Day 28 were imputed as deceased.
    Time Frame
    Up to 28 days
    Title
    Clinical Response at Test of Cure (TOC) Visit in the Intent-to-Treat (ITT) Population
    Description
    The clinical response in the ITT population at the TOC visit (derived from the Investigator's assessment at the EOT and TOC visits) was determined by the investigator to be either: clinical success, clinical failure, or indeterminate. Clinical success was declared when most or all clinical signs were completely resolved, with no new signs of infection, no additional antibiotic therapy was required, and the participant was alive. Indeterminate was declared when the investigator could not determine success or failure. Clinical failure was declared with progression, relapse, or recurrence of new symptoms of infection, or a persistence or insufficient improvement in signs and symptoms of VNP.
    Time Frame
    7-14 days after end of therapy - TOC
    Title
    Clinical Response at Test of Cure (TOC) Visit in the Clinically-Evaluable (CE) Population
    Description
    The clinical response in the CE population at the TOC visit (derived from the Investigator's assessment at the EOT and TOC visits) was determined by the investigator to be either: clinical success, clinical failure, or indeterminate. Clinical success was declared when most or all clinical signs were completely resolved, with no new signs of infection, no additional antibiotic therapy was required, and the participant was alive. Indeterminate was declared when the investigator could not determine success or failure. Clinical failure was declared with progression, relapse, or recurrence of new symptoms of infection, or a persistence or insufficient improvement in signs and symptoms of VNP.
    Time Frame
    7-14 days after end of therapy - TOC
    Title
    Number of Methicillin-Susceptible Staphylococcus Aureus (MSSA)-Infected Participants With All-Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population
    Description
    The number of MSSA-infected participants with all-cause mortality within 28 days after randomization was determined in the mITT population. Participants who had confirmed MSSA culture results from respiratory tract or pleural fluid specimens obtained within 36 hours of study Day 1 were included. Any participants who were lost to follow-up and not known to be alive or deceased by Day 28 were imputed as deceased.
    Time Frame
    Up to 28 days
    Title
    Number of Methicillin-Resistant Staphylococcus Aureus (MRSA)-Infected Participants With All-Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population
    Description
    The number of MRSA-infected participants with all-cause mortality within 28 days after randomization was determined in the mITT population. Participants who had confirmed MRSA culture results from respiratory tract or pleural fluid specimens obtained within 72 hours of study Day 1 were included. Any participants who were lost to follow-up and not known to be alive or deceased by Day 28 were imputed as deceased.
    Time Frame
    Up to 28 days
    Title
    Number of Participants With a Favorable Response at End-of-Therapy (EOT) Visit in the Microbiological Intent-to-Treat (mITT) Population
    Description
    The number of patients in the mITT population with a favorable response at EOT was determined. Favorable response included eradication (absence of the baseline pathogen) and presumed eradication (no source specimen to culture in a participant assessed as a clinical cure by the investigator).
    Time Frame
    1-3 days after completing study therapy (Days 8-10 or Days 15-17)
    Title
    Number of Participants With a Favorable Response at End-of-Therapy (EOT) Visit in the Microbiologically-Evaluable 1 (ME-1) Population
    Description
    The number of patients in the ME-1 population with a favorable response at EOT was determined. Favorable response included eradication (absence of the baseline pathogen) and presumed eradication (no source specimen to culture in a participant assessed as a clinical cure by the investigator).
    Time Frame
    1-3 days after completing study therapy (Days 8-10 or Days 15-17)
    Title
    Number of Participants With a Favorable Response at Test-of-Cure (TOC) Visit in the Microbiological Intent-to-Treat (mITT) Population
    Description
    The number of patients in the mITT population with a favorable response at TOC was determined. Favorable response included eradication (absence of the baseline pathogen) and presumed eradication (no source specimen to culture in a participant assessed as a clinical cure by the investigator).
    Time Frame
    7-14 days after end of therapy - TOC
    Title
    Number of Participants With a Favorable Response at Test-of-Cure (TOC) Visit in the Microbiologically-Evaluable 2 (ME-2) Population
    Description
    The number of patients in the ME-2 population with a favorable response at TOC was determined. Favorable response included eradication (absence of the baseline pathogen) and presumed eradication (no source specimen to culture in a participant assessed as a clinical cure by the investigator).
    Time Frame
    7-14 days after end of therapy - TOC
    Title
    Number of Participants With ≥1 Adverse Events (AEs)
    Description
    An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Safety analysis is based on actual treatment received instead of randomization.
    Time Frame
    Up to 32 days
    Title
    Number of Participants Discontinuing Study Therapy Due to an Adverse Event (AE)
    Description
    An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Safety analysis was based on actual treatment received and not randomization.
    Time Frame
    Up to 14 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Requires IV antibiotic therapy with diagnosis of ventilated nosocomial pneumonia Gram-positive bacteria on respiratory Gram stain Exclusion Criteria: Pneumonia of community, viral, fungal or parasitic etiology Structural lung abnormalities Immunosuppression Previous antibiotics for > 24 hours Expected survival of < 72 hours
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    16600048
    Citation
    Alp E, Voss A. Ventilator associated pneumonia and infection control. Ann Clin Microbiol Antimicrob. 2006 Apr 6;5:7. doi: 10.1186/1476-0711-5-7.
    Results Reference
    background
    PubMed Identifier
    15699079
    Citation
    American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005 Feb 15;171(4):388-416. doi: 10.1164/rccm.200405-644ST. No abstract available.
    Results Reference
    background
    PubMed Identifier
    14625336
    Citation
    Chastre J, Wolff M, Fagon JY, Chevret S, Thomas F, Wermert D, Clementi E, Gonzalez J, Jusserand D, Asfar P, Perrin D, Fieux F, Aubas S; PneumA Trial Group. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003 Nov 19;290(19):2588-98. doi: 10.1001/jama.290.19.2588.
    Results Reference
    background
    PubMed Identifier
    3390511
    Citation
    Lan KK, Wittes J. The B-value: a tool for monitoring data. Biometrics. 1988 Jun;44(2):579-85.
    Results Reference
    background
    PubMed Identifier
    16652315
    Citation
    Lawrence KR, Adra M, Gillman PK. Serotonin toxicity associated with the use of linezolid: a review of postmarketing data. Clin Infect Dis. 2006 Jun 1;42(11):1578-83. doi: 10.1086/503839. Epub 2006 Apr 27.
    Results Reference
    background
    PubMed Identifier
    19759040
    Citation
    Lemaire S, Van Bambeke F, Appelbaum PC, Tulkens PM. Cellular pharmacokinetics and intracellular activity of torezolid (TR-700): studies with human macrophage (THP-1) and endothelial (HUVEC) cell lines. J Antimicrob Chemother. 2009 Nov;64(5):1035-43. doi: 10.1093/jac/dkp267. Epub 2009 Sep 16.
    Results Reference
    background
    PubMed Identifier
    18989656
    Citation
    Torres A, Ewig S, Lode H, Carlet J; European HAP working group. Defining, treating and preventing hospital acquired pneumonia: European perspective. Intensive Care Med. 2009 Jan;35(1):9-29. doi: 10.1007/s00134-008-1336-9. Epub 2008 Nov 7.
    Results Reference
    background
    PubMed Identifier
    21911576
    Citation
    Drusano GL, Liu W, Kulawy R, Louie A. Impact of granulocytes on the antimicrobial effect of tedizolid in a mouse thigh infection model. Antimicrob Agents Chemother. 2011 Nov;55(11):5300-5. doi: 10.1128/AAC.00502-11. Epub 2011 Sep 12.
    Results Reference
    background
    PubMed Identifier
    21555763
    Citation
    Garonzik SM, Li J, Thamlikitkul V, Paterson DL, Shoham S, Jacob J, Silveira FP, Forrest A, Nation RL. Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob Agents Chemother. 2011 Jul;55(7):3284-94. doi: 10.1128/AAC.01733-10. Epub 2011 May 9.
    Results Reference
    background
    PubMed Identifier
    21217178
    Citation
    Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011 Feb 1;52(3):285-92. doi: 10.1093/cid/cir034.
    Results Reference
    background
    PubMed Identifier
    21163725
    Citation
    Pletz MW, Burkhardt O, Welte T. Nosocomial methicillin-resistant Staphylococcus aureus (MRSA) pneumonia: linezolid or vancomycin? - Comparison of pharmacology and clinical efficacy. Eur J Med Res. 2010 Nov 30;15(12):507-13. doi: 10.1186/2047-783x-15-12-507.
    Results Reference
    background
    PubMed Identifier
    22354302
    Citation
    Tessier PR, Keel RA, Hagihara M, Crandon JL, Nicolau DP. Comparative in vivo efficacies of epithelial lining fluid exposures of tedizolid, linezolid, and vancomycin for methicillin-resistant Staphylococcus aureus in a mouse pneumonia model. Antimicrob Agents Chemother. 2012 May;56(5):2342-6. doi: 10.1128/AAC.06427-11. Epub 2012 Feb 21.
    Results Reference
    background
    PubMed Identifier
    22247123
    Citation
    Wunderink RG, Niederman MS, Kollef MH, Shorr AF, Kunkel MJ, Baruch A, McGee WT, Reisman A, Chastre J. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis. 2012 Mar 1;54(5):621-9. doi: 10.1093/cid/cir895. Epub 2012 Jan 12.
    Results Reference
    background
    PubMed Identifier
    35718656
    Citation
    Mikamo H, Nagashima M, Kusachi S, Fujimi S, Oshima N, De Anda C, Takase A. Efficacy and safety of tedizolid for the treatment of ventilated gram-positive hospital-acquired or ventilator-associated bacterial pneumonia in Japanese patients: Results from a subgroup analysis of a phase 3, randomized, double-blind study comparing tedizolid and linezolid. J Infect Chemother. 2022 Sep;28(9):1235-1241. doi: 10.1016/j.jiac.2022.04.027. Epub 2022 Jun 16.
    Results Reference
    derived
    PubMed Identifier
    33720350
    Citation
    Wunderink RG, Roquilly A, Croce M, Rodriguez Gonzalez D, Fujimi S, Butterton JR, Broyde N, Popejoy MW, Kim JY, De Anda C. A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate and Linezolid for Treatment of Ventilated Gram-Positive Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia. Clin Infect Dis. 2021 Aug 2;73(3):e710-e718. doi: 10.1093/cid/ciab032.
    Results Reference
    derived

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    Tedizolid Phosphate (TR-701 FA, MK-1986) vs Linezolid for the Treatment of Nosocomial Pneumonia (MK-1986-002)

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