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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02019420




Registration number
NCT02019420
Ethics application status
Date submitted
18/12/2013
Date registered
24/12/2013
Date last updated
27/06/2019

Titles & IDs
Public title
Tedizolid Phosphate (TR-701 FA, MK-1986) vs Linezolid for the Treatment of Nosocomial Pneumonia (MK-1986-002)
Scientific title
A Phase 3 Randomized Double-blind Study Comparing TR-701 FA and Linezolid in Ventilated Gram-positive Nosocomial Pneumonia
Secondary ID [1] 0 0
TR701-132
Secondary ID [2] 0 0
1986-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pneumonia 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tedizolid phosphate
Treatment: Drugs - Linezolid

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

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


Treatment: Drugs: Tedizolid phosphate
Tedizolid phosphate IV 200 mg once daily

Treatment: Drugs: Linezolid
Linezolid IV 600 mg twice daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With All-Cause Mortality in the Intent-to-Treat (ITT) Population
Timepoint [1] 0 0
Up to 28 days
Secondary outcome [1] 0 0
Number of Participants With All-Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population
Timepoint [1] 0 0
Up to 28 days
Secondary outcome [2] 0 0
Clinical Response at Test of Cure (TOC) Visit in the Intent-to-Treat (ITT) Population
Timepoint [2] 0 0
7-14 days after end of therapy - TOC
Secondary outcome [3] 0 0
Clinical Response at Test of Cure (TOC) Visit in the Clinically-Evaluable (CE) Population
Timepoint [3] 0 0
7-14 days after end of therapy - TOC
Secondary outcome [4] 0 0
Number of Methicillin-Susceptible Staphylococcus Aureus (MSSA)-Infected Participants With All-Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population
Timepoint [4] 0 0
Up to 28 days
Secondary outcome [5] 0 0
Number of Methicillin-Resistant Staphylococcus Aureus (MRSA)-Infected Participants With All-Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population
Timepoint [5] 0 0
Up to 28 days
Secondary outcome [6] 0 0
Number of Participants With a Favorable Response at End-of-Therapy (EOT) Visit in the Microbiological Intent-to-Treat (mITT) Population
Timepoint [6] 0 0
1-3 days after completing study therapy (Days 8-10 or Days 15-17)
Secondary outcome [7] 0 0
Number of Participants With a Favorable Response at End-of-Therapy (EOT) Visit in the Microbiologically-Evaluable 1 (ME-1) Population
Timepoint [7] 0 0
1-3 days after completing study therapy (Days 8-10 or Days 15-17)
Secondary outcome [8] 0 0
Number of Participants With a Favorable Response at Test-of-Cure (TOC) Visit in the Microbiological Intent-to-Treat (mITT) Population
Timepoint [8] 0 0
7-14 days after end of therapy - TOC
Secondary outcome [9] 0 0
Number of Participants With a Favorable Response at Test-of-Cure (TOC) Visit in the Microbiologically-Evaluable 2 (ME-2) Population
Timepoint [9] 0 0
7-14 days after end of therapy - TOC
Secondary outcome [10] 0 0
Number of Participants With =1 Adverse Events (AEs)
Timepoint [10] 0 0
Up to 32 days
Secondary outcome [11] 0 0
Number of Participants Discontinuing Study Therapy Due to an Adverse Event (AE)
Timepoint [11] 0 0
Up to 14 days

Eligibility
Key inclusion criteria
* Requires IV antibiotic therapy with diagnosis of ventilated nosocomial pneumonia
* Gram-positive bacteria on respiratory Gram stain
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pneumonia of community, viral, fungal or parasitic etiology
* Structural lung abnormalities
* Immunosuppression
* Previous antibiotics for > 24 hours
* Expected survival of < 72 hours

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/01/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/06/2018
Sample size
Target
Accrual to date
Final
726
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT02019420
Trial related presentations / publications
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.
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.
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.
Lan KK, Wittes J. The B-value: a tool for monitoring data. Biometrics. 1988 Jun;44(2):579-85.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02019420