Back to resultsEfficacy and Safety of Intravenous to Oral 6-Day Tedizolid Phosphate vs. Intravenous to Oral 10-Day Linezolid in Patients With Acute Bacterial Skin and Skin Structure Infection (ABSSSI)
Primary Purpose
Bacterial Infections
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Tedizolid (BAY119-2631)
Placebo Tedizolid (BAY119-2631)
Linezolid
Placebo Linezolid
Sponsored by
About this trial
This is an interventional treatment trial for Bacterial Infections
Eligibility Criteria
Inclusion Criteria:
- Males or females >/=18 years old
- Adequate venous access for a minimum of 2 I.V. doses of study drug
Acute Bacterial Skin and skin structure infection (ABSSSI) meeting at least 1 of the clinical syndrome definitions listed below and requiring I.V. antibiotic therapy. Local symptoms must have started within 7 days before the Screening Visit
- Cellulitis/erysipelas
- Major cutaneous abscess
- Wound Infection
- Suspected or documented gram-positive infection from baseline Gram stain or culture.
Exclusion Criteria:
- Uncomplicated skin and skin structure infections such as furuncles, minor abscesses
- Infections associated with, or in close proximity to, a prosthetic device
- Severe sepsis or septic shock
- Known bacteremia at time of screening
ABSSSI due to or associated with any of the following:
- Suspected or documented gram-negative pathogens in patients with cellulitis/erysipelas or major cutaneous abscess that require an antibiotic with specific gram-negative coverage. Patients with wound infections where gram-negative adjunctive therapy is warranted may be enrolled if they meet the other eligibility criteria
- Diabetic foot infections, gangrene, or perianal abscess
- Concomitant infection at another site not including a secondary ABSSSI lesion (eg, septic arthritis, endocarditis, osteomyelitis)
- Infected burns
- Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease (arterial or venous)
- Any evolving necrotizing process (ie, necrotizing fasciitis)
Use of antibiotics as follows:
- Systemic antibiotic with gram-positive cocci activity for the treatment of any infection within 24 hours before the first infusion of study drug
- Patients who failed prior therapy for the primary infection site are also excluded from enrollment
- Topical antibiotic on the primary lesion within 24 hours before the first infusion of study drug except for antibiotic/antiseptic-coated dressing applied to the clean postsurgical wound
- Administration of Linezolid within 30 days before the first infusion of the study drug
- Recent history of opportunistic infections where the underlying cause of these infections is still active (eg, leukemia, transplant, acquired immunodeficiency syndrome [AIDS])
- Previous exposure to Tedizolid Phosphate treatment
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Tedizolid Phosphate (Sivextro, BAY119-2631)
Linezolid
Arm Description
Participants received 200 mg Tedizolid Phosphate once daily intravenous (I.V.) infusion to oral for 6 days, followed by 4 days of placebo.
Participants received 600 mg Linezolid twice daily I.V. infusion to oral for 10 days.
Outcomes
Primary Outcome Measures
Percentage of Participants With Early Clinical Response at 48-72 Hours After the First Infusion of Study Drug in the ITT Analysis Set.
Early clinical response is defined as responder if there is >=20% reduction in the area of erythema, edema, and/or induration (length × width) of the primary acute bacterial skin and skin structure infections (ABSSSI) lesion, compared with baseline at the 48-72 Hour visit.
Secondary Outcome Measures
Programmatically Defined Clinical Response at End of Therapy (EOT) Visit in the ITT Analysis Set
Clinical Failure: Presence of fever; No lesion size decrease from baseline; Clinician assessment of tenderness worse than mild; Persistent same or great intensity purulent drainage of wound infection; Confounding use of systemic concomitant antibiotic; TEAE lead to study drug discontinuation; Require additional antibiotic treatment for primary lesion; Unplanned major surgical intervention. Clinical Success: Afebrile or fever due to other cause; Lesion size decrease from baseline; Clinician assessment of mild/absent tenderness; None/lesser intensity purulent drainage of wound infection; None confounding use of systemic concomitant antibiotic; None TEAE leading to study drug discontinuation; No additional antibiotic therapy for primary lesion; No unplanned major surgical intervention; No osteomyelitis after baseline; For wound/abscess: no incision/drainage of the ABSSSI site after Day1 unless planned. For cellulitis/ersipelas: no incision/drainage of the ABSSSI site after 48-72 H Visit.
Programmatically Defined Clinical Response at End of Therapy (EOT) Visit in the Clinically Evaluable at EOT (CE-EOT) Analysis Set
Clinical response will be defined as percentage of participants with clinical success, clinical failure or indeterminate.
Overall Investigator's Assessment of Clinical Success at Post Therapy Evaluation (PTE) Visit (7-14 Days After EOT Visit) in the ITT Analysis Set
The Investigator made an assessment of clinical response at the PTE Visit (7-14 days after the EOT Visit +2 days). Participants assessed as a clinical failure at the EOT Visit are considered a clinical failure at the PTE Visit. Percentage of participants with clinical success, clinical failure or indeterminate were reported.
Overall Investigator's Assessment of Clinical Success at Post Therapy Evaluation (PTE) Visit (7-14 Days After EOT Visit) in the Clinically Evaluable at Post Therapy Evaluation (CE-PTE) Analysis Set
The Investigator made an assessment of clinical response at the PTE Visit (7-14 days after the EOT Visit +2 days). Participants assessed as a clinical failure at the EOT Visit are considered a clinical failure at the PTE Visit. Percentage of participants with clinical success, clinical failure or indeterminate were reported.
Investigator's Assessment of Clinical Response at 48-72 Hours
The Investigator made an assessment of clinical response at the 48-72 Hour Visit based on following definition: Improving (Improvement in overall clinical status of ABSSSI compatible with continuation of study drug therapy); Stable (Signs and symptoms stable, no apparent change in overall clinical status but compatible with continuation of study drug therapy); Other.
Investigator's Assessment of Clinical Response at Day 7 Visit
The Investigator made an assessment of clinical response at Day 7 Visit based on following definition: Improving (Improvement in overall clinical status of ABSSSI compatible with continuation of study drug therapy); Other.
Value of the Visual Analog Scale (VAS) Pain Scores at Each Time Point
The patient-reported level of pain were assessed by the visual analog scale (VAS) pain score. VAS pain score ranged from 0 mm (no pain) to 100 mm (worst pain ever). It used a 100 mm VAS to instruct the patient to indicate the point along the line that represents the pain they are feeling. Once the patient indicates how much pain they are feeling, measure the distance from no pain and enter the value.
Change From Baseline in the Visual Analog Scale (VAS) Pain Scores at Each Time Point
The patient-reported level of pain were assessed by the visual analog scale (VAS) pain score. VAS pain score ranged from 0 mm (no pain) to 100 mm (worst pain ever). It used a 100 mm VAS to instruct the patient to indicate the point along the line that represents the pain they are feeling. Once the patient indicates how much pain they are feeling, measure the distance from no pain and enter the value.
Value of the Faces Rating Scale (FRS) Pain Scores at Each Time Point
The patient-reported level of pain were assessed by the faces rating scale (FRS) pain score. Ask the patient to rate their pain from 0 to 10 with 0 being no pain at all and 10 being the worst pain then enter the numerical value.
Change From Baseline in the Faces Rating Scale (FRS) Pain Scores at Each Time Point
The patient-reported level of pain were assessed by the faces rating scale (FRS) pain score. The patient-reported level of pain were assessed by the faces rating scale (FRS) pain score. Ask the patient to rate their pain from 0 to 10 with 0 being no pain at all and 10 being the worst pain then enter the numerical value.
Full Information
NCT ID
NCT02066402
First Posted
February 17, 2014
Last Updated
May 5, 2017
Sponsor
Bayer
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT02066402
Brief Title
Efficacy and Safety of Intravenous to Oral 6-Day Tedizolid Phosphate vs. Intravenous to Oral 10-Day Linezolid in Patients With Acute Bacterial Skin and Skin Structure Infection (ABSSSI)
Official Title
A Phase 3 Randomized, Double-Blind, Multicenter Study Comparing the Efficacy and Safety of Intravenous to Oral 6-Day Tedizolid Phosphate and Intravenous to Oral 10-Day Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infections
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
March 4, 2014 (Actual)
Primary Completion Date
March 6, 2016 (Actual)
Study Completion Date
April 18, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is aimed to evaluate the efficacy and safety between Tedizolid 200mg daily (intra venous) I.V. to oral for 6-day treatment compared with that of Linezolid 600mg twice daily I.V. to oral for 10-day treatment Acute Bacterial Skin and skin structure infection (ABSSSI).This is a double-blind, randomized, active control, 7-10days treatment for all subjects.
Detailed Description
Number of participants with adverse evnets as a measure of safety and tolerability will be covered in Adverse Events section.
ABSSSI Efficacy Safety Tedizolid Phosphate Linezolid
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bacterial Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
598 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tedizolid Phosphate (Sivextro, BAY119-2631)
Arm Type
Experimental
Arm Description
Participants received 200 mg Tedizolid Phosphate once daily intravenous (I.V.) infusion to oral for 6 days, followed by 4 days of placebo.
Arm Title
Linezolid
Arm Type
Active Comparator
Arm Description
Participants received 600 mg Linezolid twice daily I.V. infusion to oral for 10 days.
Intervention Type
Drug
Intervention Name(s)
Tedizolid (BAY119-2631)
Intervention Description
50 % of the participants will be randomized to this arm and will receive 200 mg Tedizolid once daily i.v to oral from 1-6 days
Intervention Type
Drug
Intervention Name(s)
Placebo Tedizolid (BAY119-2631)
Intervention Description
50 % of the participants will be randomized to this arm and will receive 200 mg Placebo Tedizolid once daily i.v to oral from 7-10 days
Intervention Type
Drug
Intervention Name(s)
Linezolid
Intervention Description
50 % of the participants will be randomized to this arm and will receive 600 mg Linezolid twice daily i.v. to oral from 1-10 days
Intervention Type
Drug
Intervention Name(s)
Placebo Linezolid
Intervention Description
50 % of the participants will be randomized to this arm and will receive 600 mg Placebo Linezolid twice daily i.v. to oral from 1-10 days
Primary Outcome Measure Information:
Title
Percentage of Participants With Early Clinical Response at 48-72 Hours After the First Infusion of Study Drug in the ITT Analysis Set.
Description
Early clinical response is defined as responder if there is >=20% reduction in the area of erythema, edema, and/or induration (length × width) of the primary acute bacterial skin and skin structure infections (ABSSSI) lesion, compared with baseline at the 48-72 Hour visit.
Time Frame
Baseline and 48-72 hours visit
Secondary Outcome Measure Information:
Title
Programmatically Defined Clinical Response at End of Therapy (EOT) Visit in the ITT Analysis Set
Description
Clinical Failure: Presence of fever; No lesion size decrease from baseline; Clinician assessment of tenderness worse than mild; Persistent same or great intensity purulent drainage of wound infection; Confounding use of systemic concomitant antibiotic; TEAE lead to study drug discontinuation; Require additional antibiotic treatment for primary lesion; Unplanned major surgical intervention. Clinical Success: Afebrile or fever due to other cause; Lesion size decrease from baseline; Clinician assessment of mild/absent tenderness; None/lesser intensity purulent drainage of wound infection; None confounding use of systemic concomitant antibiotic; None TEAE leading to study drug discontinuation; No additional antibiotic therapy for primary lesion; No unplanned major surgical intervention; No osteomyelitis after baseline; For wound/abscess: no incision/drainage of the ABSSSI site after Day1 unless planned. For cellulitis/ersipelas: no incision/drainage of the ABSSSI site after 48-72 H Visit.
Time Frame
Baseline and EOT visit (Day 11)
Title
Programmatically Defined Clinical Response at End of Therapy (EOT) Visit in the Clinically Evaluable at EOT (CE-EOT) Analysis Set
Description
Clinical response will be defined as percentage of participants with clinical success, clinical failure or indeterminate.
Time Frame
Baseline and EOT visit (Day 11)
Title
Overall Investigator's Assessment of Clinical Success at Post Therapy Evaluation (PTE) Visit (7-14 Days After EOT Visit) in the ITT Analysis Set
Description
The Investigator made an assessment of clinical response at the PTE Visit (7-14 days after the EOT Visit +2 days). Participants assessed as a clinical failure at the EOT Visit are considered a clinical failure at the PTE Visit. Percentage of participants with clinical success, clinical failure or indeterminate were reported.
Time Frame
Baseline and post-therapy evaluation visit (7-14 days after Day 11)
Title
Overall Investigator's Assessment of Clinical Success at Post Therapy Evaluation (PTE) Visit (7-14 Days After EOT Visit) in the Clinically Evaluable at Post Therapy Evaluation (CE-PTE) Analysis Set
Description
The Investigator made an assessment of clinical response at the PTE Visit (7-14 days after the EOT Visit +2 days). Participants assessed as a clinical failure at the EOT Visit are considered a clinical failure at the PTE Visit. Percentage of participants with clinical success, clinical failure or indeterminate were reported.
Time Frame
Baseline and post-therapy evaluation visit (7-14 days after Day 11)
Title
Investigator's Assessment of Clinical Response at 48-72 Hours
Description
The Investigator made an assessment of clinical response at the 48-72 Hour Visit based on following definition: Improving (Improvement in overall clinical status of ABSSSI compatible with continuation of study drug therapy); Stable (Signs and symptoms stable, no apparent change in overall clinical status but compatible with continuation of study drug therapy); Other.
Time Frame
Baseline and at 48-72 hours
Title
Investigator's Assessment of Clinical Response at Day 7 Visit
Description
The Investigator made an assessment of clinical response at Day 7 Visit based on following definition: Improving (Improvement in overall clinical status of ABSSSI compatible with continuation of study drug therapy); Other.
Time Frame
Baseline and Day 7 visit
Title
Value of the Visual Analog Scale (VAS) Pain Scores at Each Time Point
Description
The patient-reported level of pain were assessed by the visual analog scale (VAS) pain score. VAS pain score ranged from 0 mm (no pain) to 100 mm (worst pain ever). It used a 100 mm VAS to instruct the patient to indicate the point along the line that represents the pain they are feeling. Once the patient indicates how much pain they are feeling, measure the distance from no pain and enter the value.
Time Frame
Up to EOT visit (Day 11)
Title
Change From Baseline in the Visual Analog Scale (VAS) Pain Scores at Each Time Point
Description
The patient-reported level of pain were assessed by the visual analog scale (VAS) pain score. VAS pain score ranged from 0 mm (no pain) to 100 mm (worst pain ever). It used a 100 mm VAS to instruct the patient to indicate the point along the line that represents the pain they are feeling. Once the patient indicates how much pain they are feeling, measure the distance from no pain and enter the value.
Time Frame
Up to EOT visit (Day 11)
Title
Value of the Faces Rating Scale (FRS) Pain Scores at Each Time Point
Description
The patient-reported level of pain were assessed by the faces rating scale (FRS) pain score. Ask the patient to rate their pain from 0 to 10 with 0 being no pain at all and 10 being the worst pain then enter the numerical value.
Time Frame
Up to EOT visit (Day 11)
Title
Change From Baseline in the Faces Rating Scale (FRS) Pain Scores at Each Time Point
Description
The patient-reported level of pain were assessed by the faces rating scale (FRS) pain score. The patient-reported level of pain were assessed by the faces rating scale (FRS) pain score. Ask the patient to rate their pain from 0 to 10 with 0 being no pain at all and 10 being the worst pain then enter the numerical value.
Time Frame
Up to EOT visit (Day 11)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males or females >/=18 years old
Adequate venous access for a minimum of 2 I.V. doses of study drug
Acute Bacterial Skin and skin structure infection (ABSSSI) meeting at least 1 of the clinical syndrome definitions listed below and requiring I.V. antibiotic therapy. Local symptoms must have started within 7 days before the Screening Visit
Cellulitis/erysipelas
Major cutaneous abscess
Wound Infection
Suspected or documented gram-positive infection from baseline Gram stain or culture.
Exclusion Criteria:
Uncomplicated skin and skin structure infections such as furuncles, minor abscesses
Infections associated with, or in close proximity to, a prosthetic device
Severe sepsis or septic shock
Known bacteremia at time of screening
ABSSSI due to or associated with any of the following:
Suspected or documented gram-negative pathogens in patients with cellulitis/erysipelas or major cutaneous abscess that require an antibiotic with specific gram-negative coverage. Patients with wound infections where gram-negative adjunctive therapy is warranted may be enrolled if they meet the other eligibility criteria
Diabetic foot infections, gangrene, or perianal abscess
Concomitant infection at another site not including a secondary ABSSSI lesion (eg, septic arthritis, endocarditis, osteomyelitis)
Infected burns
Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease (arterial or venous)
Any evolving necrotizing process (ie, necrotizing fasciitis)
Use of antibiotics as follows:
Systemic antibiotic with gram-positive cocci activity for the treatment of any infection within 24 hours before the first infusion of study drug
Patients who failed prior therapy for the primary infection site are also excluded from enrollment
Topical antibiotic on the primary lesion within 24 hours before the first infusion of study drug except for antibiotic/antiseptic-coated dressing applied to the clean postsurgical wound
Administration of Linezolid within 30 days before the first infusion of the study drug
Recent history of opportunistic infections where the underlying cause of these infections is still active (eg, leukemia, transplant, acquired immunodeficiency syndrome [AIDS])
Previous exposure to Tedizolid Phosphate treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
City
Oceanside
State/Province
California
ZIP/Postal Code
92056
Country
United States
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89109
Country
United States
City
Teaneck
State/Province
New Jersey
ZIP/Postal Code
07666
Country
United States
City
Wuhu
State/Province
Anhui
ZIP/Postal Code
241001
Country
China
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350025
Country
China
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510120
Country
China
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510180
Country
China
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410005
Country
China
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410015
Country
China
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
City
Nanjing
State/Province
Jiangsu
Country
China
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
City
Wuxi
State/Province
Jiangsu
Country
China
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
City
Dalian
State/Province
Liaoning
ZIP/Postal Code
116027
Country
China
City
Shenyang
State/Province
Liaoning
ZIP/Postal Code
110001
Country
China
City
Shenyang
State/Province
Liaoning
ZIP/Postal Code
110016
Country
China
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710038
Country
China
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710061
Country
China
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250012
Country
China
City
Taiyuan
State/Province
Shanxi
ZIP/Postal Code
030001
Country
China
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
City
Urumchi
State/Province
Xinjiang
ZIP/Postal Code
830054
Country
China
City
Urumqi
State/Province
Xinjiang
ZIP/Postal Code
830054
Country
China
City
Kunming
State/Province
Yunnan
ZIP/Postal Code
650032
Country
China
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310009
Country
China
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310014
Country
China
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310016
Country
China
City
Beijing
ZIP/Postal Code
100034
Country
China
City
Beijing
ZIP/Postal Code
100044
Country
China
City
Beijing
ZIP/Postal Code
100050
Country
China
City
Beijing
ZIP/Postal Code
100191
Country
China
City
Beijing
ZIP/Postal Code
100730
Country
China
City
Chongqing
ZIP/Postal Code
400042
Country
China
City
Shanghai
ZIP/Postal Code
200003
Country
China
City
Shanghai
ZIP/Postal Code
200025
Country
China
City
Shanghai
ZIP/Postal Code
200062
Country
China
City
Shanghai
ZIP/Postal Code
200092
Country
China
City
Shanghai
ZIP/Postal Code
201406
Country
China
City
Shanghai
ZIP/Postal Code
201700
Country
China
City
Tianjin
ZIP/Postal Code
300052
Country
China
City
Tianjin
ZIP/Postal Code
300121
Country
China
City
Quezon City
Country
Philippines
City
Taguig City
Country
Philippines
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
City
Kaohsiung
ZIP/Postal Code
81362
Country
Taiwan
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
City
Tainan
ZIP/Postal Code
710
Country
Taiwan
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
City
Taipei
ZIP/Postal Code
116
Country
Taiwan
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan
12. IPD Sharing Statement
Citations:
PubMed Identifier
30988146
Citation
Lv X, Alder J, Li L, O'Riordan W, Rybak MJ, Ye H, Zhang R, Zhang Z, Zhu X, Wilcox MH. Efficacy and Safety of Tedizolid Phosphate versus Linezolid in a Randomized Phase 3 Trial in Patients with Acute Bacterial Skin and Skin Structure Infection. Antimicrob Agents Chemother. 2019 Jun 24;63(7):e02252-18. doi: 10.1128/AAC.02252-18. Print 2019 Jul.
Results Reference
derived
Learn more about this trial
Efficacy and Safety of Intravenous to Oral 6-Day Tedizolid Phosphate vs. Intravenous to Oral 10-Day Linezolid in Patients With Acute Bacterial Skin and Skin Structure Infection (ABSSSI)
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