Clinical trial NCT01421511: TR-701 FA vs Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infections
Official title: A Phase 3 Randomized, Double-Blind, Multicenter Study Comparing the Efficacy and Safety of IV to Oral 6-Day TR-701 Free Acid and IV to Oral 10-Day Linezolid for the Treatment of ABSSSI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Skin and Subcutaneous Tissue Bacterial Infections
Keywords: ABSSSI
Tedizolid Phosphate
TR-701
Acute Bacterial Skin and Skin Structure Infections
Lead sponsor: Trius Therapeutics LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2011-08-22
Enrollment: 666
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 randomized, double-blind, double-dummy, multicenter, global Phase 3 study of IV to oral TR-701 FA 200 mg once daily for 6 days versus IV to oral Zyvox® (linezolid) 600 mg every 12 hours for 10 days for the treatment of ABSSSI in adults. Patients are to start treatment with at least 2 IV doses and may receive IV therapy for the entire treatment duration.

Approximately 100 to 140 sites globally will participate in this study. Patients with an ABSSSI caused by suspected or documented gram positive pathogen(s) at baseline will be randomized 1:1 to study treatment.

Detailed description: The primary objective is to determine the noninferiority (NI) in the early clinical response rate of intravenous (IV) to oral 6 day TR-701 free acid (FA) compared with that of IV to oral 10-day linezolid treatment at 48-72 hours after the first infusion of study drug in the intent-to-treat (ITT) analysis set in patients with acute bacterial skin and skin structure infections (ABSSSI).

Eligibility criteria: Inclusion Criteria:

* Patients requiring IV antibiotic therapy and with systemic signs of infection diagnosed with ABSSSI.
* Diagnosed with Cellulitis/ erysipelas, major cutaneous abscess, or wound infections

Exclusion Criteria:

* Uncomplicated skin infections
* Severe sepsis or septic shock
* ABSSSI solely due to gram-negative pathogens

Primary outcomes:
measure: The Early Clinical Response Rate
timeFrame: 48-72 hours
Secondary outcomes:
measure: Clinical Response at the End of Therapy Visit
timeFrame: Day 11
measure: Clinical Response at the End of Therapy Visit in the Clinically Evaluable at End of Therapy Analysis Set
timeFrame: End of Therapy Day 11
measure: Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit
timeFrame: Post-Treatment Evaluation (7-14 days after the End of Therapy)
measure: Investigator's Assessment of Clinical Success of the Post Therapy Evaluation Visit in Clinically Evaluable-Post Treatment Evaluation Analysis Set.
timeFrame: Post-Treatment Evaluation (7-14 days after the End of Therapy)
measure: Investigator's Assessment of Clinical Response at the 48-72 Hour Visit
timeFrame: 48-72 Hours
measure: Investigator's Assessment of Clinical Response at the Day-7 Visit
timeFrame: Day 7
measure: Change From Baseline in Patient-reported Pain, by Study Visit
timeFrame: Multiple
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Trius investigator site 159
state: Alabama
city: Chula Vista
country: United States
facility: Trius investigator site 103
state: California
city: Escondido
country: United States
facility: Trius investigator site 143
state: California
city: La Mesa
country: United States
facility: Trius investigator site 105
state: California
city: Long Beach
country: United States
facility: Trius investigator site 106
state: California
city: Long Beach
country: United States
facility: Trius investigator site 157
state: California
city: National City
country: United States
facility: Trius investigator site 142
state: California
city: San Diego
country: United States
facility: Trius investigator site 170
state: California
city: Santa Ana
country: United States
facility: Trius investigator site 167
state: California
city: Stockton
country: United States
facility: Trius investigator site 168
state: California
city: Sylmar
country: United States
facility: Trius investigator site 141
state: California
city: Denver
country: United States
facility: Trius investigator site 139
state: Colorado
city: Newark
country: United States
facility: Trius investigator site 137
state: Delaware
city: Edgewater
country: United States
facility: Trius investigator site 166
state: Florida
city: Columbus
country: United States
facility: Trius investigator site 101
state: Georgia
city: Carmel
country: United States
facility: Trius investigator site 138
state: Indiana
city: Owensboro
country: United States
facility: Trius investigator site 144
state: Kentucky
city: Baton Rouge
country: United States
facility: Trius investigator site 150
state: Louisiana
city: Eunice
country: United States
facility: Trius investigator site 165
state: Louisiana
city: Boston
country: United States
facility: Trius investigator site 154
state: Massachusetts
city: Springfield
country: United States
facility: Trius investigator site 146
state: Massachusetts
city: West Roxbury
country: United States
facility: Trius investigator site 136
state: Massachusetts
city: Royal Oak
country: United States
facility: Trius investigator site 163
state: Michigan
city: Minneapolis
country: United States
facility: Trius investigator site 153
state: Minnesota
city: Picayune
country: United States
facility: Trius investigator site 149
state: Mississippi
city: Creve Coeur
country: United States
facility: Trius investigator site 164
state: Missouri
city: Las Vegas
country: United States
facility: Trius investigator site 160
state: Nevada
city: Teaneck
country: United States
facility: Trius investigator site 147
state: New Jersey
city: Columbus
country: United States
facility: Trius investigator site 140
state: Ohio
city: Lima
country: United States
facility: Trius investigator site 162
state: Ohio
city: Rapid City
country: United States
facility: Trius investigator site 161
state: South Dakota
city: Franklin
country: United States
facility: Trius investigator site 155
state: Tennessee
city: Memphis
country: United States
facility: Trius investigator site 145
state: Tennessee
city: Smyrna
country: United States
facility: Trius investigator site 169
state: Tennessee
city: Houston
country: United States
facility: Trius investigator site 148
state: Texas
city: Cludadela
country: Argentina
facility: Trius investigator site 352
state: Buenos Aires
city: General Roriquez
country: Argentina
facility: Trius investigator site 354
state: Buenos Aires
city: La Plata
country: Argentina
facility: Trius investigator site 350
state: Buenos Aires
city: La Plata
country: Argentina
facility: Trius investigator site 350
state: Buenos Aires
city: Lujan
country: Argentina
facility: Trius investigator site 353
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Trius investigator site 354
city: Buenos Aires
country: Argentina
facility: Trius investigator site 355
city: Cludad Autonoma De Buenos Aires
country: Argentina
facility: Trius investigator site 351
city: La Plata
country: Argentina
facility: Trius investigator site 358
city: Mar del Plata
country: Argentina
facility: Trius investigator site 357
city: Paraná, Entre Rios
country: Argentina
facility: Trius investigator site 359
city: Rosario
country: Argentina
facility: Trius investigator site 356
city: Cairns
country: Australia
facility: Trius investigator 500
state: Queensland
city: Herston
country: Australia
facility: Trius investigator 501
state: Queensland
city: Nambour
country: Australia
facility: Trius investigator 503
state: Queensland
city: Southport
country: Australia
facility: Trius investigator 506
state: Queensland
city: Woolloongabba
country: Australia
facility: Trius investigator 502
state: Queensland
city: Woolloongabba
country: Australia
facility: Trius investigator 504
state: Queensland
city: Richmond
country: Australia
facility: Trius investigator 505
state: Victoria
city: Belo Horizonte
country: Brazil
facility: Trius investigator site 362
state: MG, Brazil
city: Belo Horizonte
country: Brazil
facility: Trius investigator site 361
state: MG, Brazil
city: Porto Alegre
country: Brazil
facility: Trius investigator site 363
state: RS, Brazil
city: Campinas
country: Brazil
facility: Trius investigator site 364
state: SP, Brazil
city: Belo Horizonte
country: Brazil
facility: Trius investigator site 361
city: Belo Horizonte
country: Brazil
facility: Trius investigator site 362
city: Belo Horizonte
country: Brazil
facility: Trius investigator site 365
city: Campinas
country: Brazil
facility: Trius investigator site 364
city: Curitiba
country: Brazil
facility: Trius investigator site 366
city: Curitiba
country: Brazil
facility: Trius investigator site 367
city: Jaú
country: Brazil
facility: Trius investigator site 369
city: Porto Alegre
country: Brazil
facility: Trius investigator site 363
city: Porto Alegre
country: Brazil
facility: Trius investigator site 370
city: São Paulo
country: Brazil
facility: Trius investigator site 360
city: Quedlinburg
country: Germany
facility: Trius investigator site 206
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Trius investigator site 208
state: Sachsen
city: Luebeck
country: Germany
facility: Trius investigator site 204
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Trius investigator site 207
city: Hamburg
country: Germany
facility: Trius investigator site 205
city: Guadalajara
country: Mexico
facility: Trius investigator site 380
city: Guadalajara
country: Mexico
facility: Trius investigator site 381
city: Mexico, DF
country: Mexico
facility: Trius investigator site 382
city: Monterrey
country: Mexico
facility: Trius investigator site 383
city: Otahuhu
country: New Zealand
facility: Trius investigator 521
state: Auckland
city: Sydenham
country: New Zealand
facility: Trius investigator 520
state: Christchurch
city: Bydgoszcz
country: Poland
facility: Trius investigator site 216
city: Lodz
country: Poland
facility: Trius investigator site 211
city: Lublin
country: Poland
facility: Trius investigator site 214
city: Poznan
country: Poland
facility: Trius investigator site 213
city: Szczecin
country: Poland
facility: Trius investigator site 215
city: Warszawa
country: Poland
facility: Trius investigator site 212
city: Vsevolozhsk
country: Russian Federation
facility: Trius investigator site 292
state: Leningrad Region
city: Barmaul
country: Russian Federation
facility: Trius investigator site 287
city: Irkutsk
country: Russian Federation
facility: Trius investigator site 286
city: Lipetsk
country: Russian Federation
facility: Trius investigator site 293
city: Moscow
country: Russian Federation
facility: Trius investigator site 295
city: Moscow
country: Russian Federation
facility: Trius investigator site 290
city: Moscow
country: Russian Federation
facility: Trius investigator site 291
city: Moscow
country: Russian Federation
facility: Trius investigator site 288
city: Novosibirsk
country: Russian Federation
facility: Trius investigator site 297
city: Novosibirsk
country: Russian Federation
facility: Trius investigator site 285
city: saint-Petersburg
country: Russian Federation
facility: Trius investigator site 294
city: Saint-Petersburg
country: Russian Federation
facility: Trius investigator site 289
city: Saint-Petersburg
country: Russian Federation
facility: Trius investigator site 296
city: St-Petersburg
country: Russian Federation
facility: Trius investigator site 289
city: Tomsk
country: Russian Federation
facility: Trius investigator site 298
city: Worscester
country: South Africa
facility: Trius investigator 444
state: Cape
city: Port Elizabeth
country: South Africa
facility: Trius investigator 443
state: Eastern Cape
city: Bloemfontein
country: South Africa
facility: Trius investigator site 442
state: Free States
city: Blowmfontein
country: South Africa
facility: Trius investigator site 441
state: Free States
city: Centurion
country: South Africa
facility: Trius investigator 451
state: Gauteng
city: Gezina Pretoria
country: South Africa
facility: Trius investigator site 440
state: Gauteng
city: Pretoria
country: South Africa
facility: Trius investigator 450
state: Gauteng
city: Pretoria
country: South Africa
facility: Trius investigator 449
state: Gauteng
city: Dundee
country: South Africa
facility: Trius investigator 448
state: Kwa Zulu Natal
city: Middelburg
country: South Africa
facility: Trius investigator 446
state: Mpumalanga
city: Breyten
country: South Africa
facility: Trius investigator 447
state: Mpunalanga
city: Benoni
country: South Africa
facility: Trius investigator site 445
city: Mataro
country: Spain
facility: Trius investigator site 273
state: Barcelona
city: Alcorcon
country: Spain
facility: Trius investigator site 272
state: Madrid
city: Majadahonda
country: Spain
facility: Trius investigator site 275
state: Madrid
city: Baracaldo
country: Spain
facility: Trius investigator site 277
state: Vizcaya
city: Madrid
country: Spain
facility: Trius investigator site 276
city: Santander
country: Spain
facility: Trius investigator site 274
Study officials:
affiliation: Trius Therapeutics
name: Philippe G Prokocimer, MD
role: STUDY_DIRECTOR
References:
citation: Sandison T, De Anda C, Fang E, Das AF, Prokocimer P. Clinical Response of Tedizolid versus Linezolid in Acute Bacterial Skin and Skin Structure Infections by Severity Measure Using a Pooled Analysis from Two Phase 3 Double-Blind Trials. Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02687-16. doi: 10.1128/AAC.02687-16. Print 2017 May.
citation: Nathwani D, Corey R, Das AF, Sandison T, De Anda C, Prokocimer P. Early Clinical Response as a Predictor of Late Treatment Success in Patients With Acute Bacterial Skin and Skin Structure Infections: Retrospective Analysis of 2 Randomized Controlled Trials. Clin Infect Dis. 2017 Jan 15;64(2):214-217. doi: 10.1093/cid/ciw750. Epub 2016 Dec 21.
citation: Powers JH 3rd, Das AF, De Anda C, Prokocimer P. Clinician-reported lesion measurements in skin infection trials: Definitions, reliability, and association with patient-reported pain. Contemp Clin Trials. 2016 Sep;50:265-72. doi: 10.1016/j.cct.2016.08.010. Epub 2016 Aug 13.
citation: Shorr AF, Lodise TP, Corey GR, De Anda C, Fang E, Das AF, Prokocimer P. Analysis of the phase 3 ESTABLISH trials of tedizolid versus linezolid in acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2015 Feb;59(2):864-71. doi: 10.1128/AAC.03688-14. Epub 2014 Nov 24.
citation: Lodise TP, Fang E, Minassian SL, Prokocimer PG. Platelet profile in patients with acute bacterial skin and skin structure infections receiving tedizolid or linezolid: findings from the Phase 3 ESTABLISH clinical trials. Antimicrob Agents Chemother. 2014 Dec;58(12):7198-204. doi: 10.1128/AAC.03509-14. Epub 2014 Sep 22.
citation: Moran GJ, Fang E, Corey GR, Das AF, De Anda C, Prokocimer P. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2014 Aug;14(8):696-705. doi: 10.1016/S1473-3099(14)70737-6. Epub 2014 Jun 5.