Clinical trial NCT02019420: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2013-12-24
Enrollment: 726
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Number of Participants With All-Cause Mortality in the Intent-to-Treat (ITT) Population
timeFrame: Up to 28 days
Secondary outcomes:
measure: Number of Participants With All-Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population
timeFrame: Up to 28 days
measure: Clinical Response at Test of Cure (TOC) Visit in the Intent-to-Treat (ITT) Population
timeFrame: 7-14 days after end of therapy - TOC
measure: Clinical Response at Test of Cure (TOC) Visit in the Clinically-Evaluable (CE) Population
timeFrame: 7-14 days after end of therapy - TOC
measure: Number of Methicillin-Susceptible Staphylococcus Aureus (MSSA)-Infected Participants With All-Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population
timeFrame: Up to 28 days
measure: Number of Methicillin-Resistant Staphylococcus Aureus (MRSA)-Infected Participants With All-Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population
timeFrame: Up to 28 days
measure: Number of Participants With a Favorable Response at End-of-Therapy (EOT) Visit in the Microbiological Intent-to-Treat (mITT) Population
timeFrame: 1-3 days after completing study therapy (Days 8-10 or Days 15-17)
measure: Number of Participants With a Favorable Response at End-of-Therapy (EOT) Visit in the Microbiologically-Evaluable 1 (ME-1) Population
timeFrame: 1-3 days after completing study therapy (Days 8-10 or Days 15-17)
measure: Number of Participants With a Favorable Response at Test-of-Cure (TOC) Visit in the Microbiological Intent-to-Treat (mITT) Population
timeFrame: 7-14 days after end of therapy - TOC
measure: Number of Participants With a Favorable Response at Test-of-Cure (TOC) Visit in the Microbiologically-Evaluable 2 (ME-2) Population
timeFrame: 7-14 days after end of therapy - TOC
measure: Number of Participants With ≥1 Adverse Events (AEs)
timeFrame: Up to 32 days
measure: Number of Participants Discontinuing Study Therapy Due to an Adverse Event (AE)
timeFrame: Up to 14 days
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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