Abscess, Cellulitis, Surgical Site Infection, Wound Infection
Conditions
Brief summary
The primary object is to compare the early clinical efficacy (after 48-72 hours of therapy) of dalbavancin to the comparator regimen (vancomycin with the option to switch to oral linezolid) for the treatment of patients with a suspected or proven gram-positive bacterial skin or skin structure infection.
Interventions
DRUGDalbavancin
IV Dalbavancin 1000 mg on Day 1 and 500 mg on Day 8
DRUGVancomycin / Linezolid
IV Vancomycin (1 gram Q 12 hours or 15mg/Kg Q 12 hours) with optional switch to oral linezolid (600 mg Q12 hours). Total duration of therapy is 10-14 days.
Sponsors
Durata Therapeutics Inc., an affiliate of Allergan plc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients 18 - 85 years of age. 2. Signed and dated informed consent document. 3. Major abscess, surgical site infection, traumatic wound infection or cellulitis suspected or confirmed to be caused by Gram-positive bacteria. 4. At least two (2) local signs and symptoms of ABSSSI and at least one (1) systemic sign of infection. 5. Requires a minimum of 3 days of IV therapy. 6. Patient willing and able to comply with study procedures.
Exclusion criteria
Patients presenting with any of the following: 1. A contra-indication to any required study drug. 2. Pregnant or nursing females. 3. Sustained shock. 4. Participation in another study of an investigational drug or device within 30 days. 5. Receipt of a systemically or topically administered antibiotic within 14 days prior to randomization, except receipt of a single dose of a short-acting antibacterial drug 3 or more days prior to randomization. 6. Infection due to a dalbavancin or vancomycin-resistant organism. 7. Evidence of meningitis, necrotizing fasciitis, gas gangrene, gangrene, septic arthritis, osteomyelitis, and/or endovascular infection. 8. Exclusively gram-negative bacterial or a fungal ABSSSI. 9. Venous catheter infection. 10. Infection of a diabetic foot ulcer or a decubitus ulcer. 11. Device-related infections. 12. Gram-negative bacteremia. 13. Infected burns. 14. Infected limb with critical ischemia. 15. Superficial/simple skin and skin structure infections. 16. Concomitant condition requiring non-study antibacterial therapy. 17. ABSSSI requiring therapy for longer than 14 days. 18. Adjunctive therapy with hyperbaric oxygen. 19. More than 2 surgical interventions for ABSSSI anticipated. 20. Chronic inflammatory condition precluding assessment of clinical response. 21. Absolute neutrophil count \< 500 cells/mm3. 22. Human immunodeficiency virus (HIV) infection with a CD4 cell count \< 200 cells/mm3. 23. Recent bone marrow transplant, \> 20 mg prednisolone per day (or equivalent) or receiving immunosuppressant drugs after organ transplantation. 24. Regular, chronic antipyretic use in patients unable to modify during the first three days of study drug therapy. 25. Life expectancy less than 3 months. 26. Conditions that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results. 27. Prior participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Early Clinical Efficacy | 48-72 hours after the initiation of study therapy | Clinical response at 48-72 hours post study drug initiation, based on measurements of acute bacterial skin and skin structure infections (ABSSSI) lesion size and temperature |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| >= 20% Reduction in Lesion Area | 48-72 hours after the initiation of study therapy | Clinical response at 48-72 hours post study drug initiation, based on measurements of acute bacterial skin and skin structure infections (ABSSSI) lesion size |
| Clinical Status | End of Treatment Visit (Day 14-15) | Compare the clinical efficacy at end of treatment visit of dalbavancin to the comparator regimen based on lesion size, local signs, temperature and receipt of non-study antibiotics |
Countries
Canada, Croatia, Georgia, Germany, Poland, Russia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dalbavancin Dalbavancin : IV Dalbavancin 1000 mg on Day 1 and 500 mg on Day 8 | 288 |
| Vancomycin +/- Oral Linezolid Vancomycin : IV Vancomycin (dosed per standard of care) with optional switch to oral linezolid (600 mg Q12 hours). Total duration of therapy is 10-14 days. | 285 |
| Total | 573 |
Baseline characteristics
| Characteristic | Dalbavancin | Vancomycin +/- Oral Linezolid | Total |
|---|---|---|---|
| Age, Continuous | 48.8 years STANDARD_DEVIATION 15.3 | 48.9 years STANDARD_DEVIATION 15.08 | 48.9 years STANDARD_DEVIATION 15.18 |
| Sex: Female, Male Female | 118 Participants | 112 Participants | 230 Participants |
| Sex: Female, Male Male | 170 Participants | 173 Participants | 343 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 284 | 54 / 284 |
| serious Total, serious adverse events | 5 / 284 | 12 / 284 |
Outcome results
Primary
Early Clinical Efficacy
Clinical response at 48-72 hours post study drug initiation, based on measurements of acute bacterial skin and skin structure infections (ABSSSI) lesion size and temperature
Time frame: 48-72 hours after the initiation of study therapy
Population: The ITT population consisted of all randomly assigned patients regardless of whether or not they received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalbavancin | Early Clinical Efficacy | Clinical Responder | 240 participants |
| Dalbavancin | Early Clinical Efficacy | Clinical Non-Responder | 48 participants |
| Vancomycin +/- Oral Linezolid | Early Clinical Efficacy | Clinical Responder | 233 participants |
| Vancomycin +/- Oral Linezolid | Early Clinical Efficacy | Clinical Non-Responder | 52 participants |
95% CI: [-4.6, 7.9]
Secondary
>= 20% Reduction in Lesion Area
Clinical response at 48-72 hours post study drug initiation, based on measurements of acute bacterial skin and skin structure infections (ABSSSI) lesion size
Time frame: 48-72 hours after the initiation of study therapy
Population: The ITT population consisted of all randomly assigned patients regardless of whether or not they received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalbavancin | >= 20% Reduction in Lesion Area | Clinical Responder | 259 participants |
| Dalbavancin | >= 20% Reduction in Lesion Area | Clinical Non-Responder | 29 participants |
| Vancomycin +/- Oral Linezolid | >= 20% Reduction in Lesion Area | Clinical Responder | 259 participants |
| Vancomycin +/- Oral Linezolid | >= 20% Reduction in Lesion Area | Clinical Non-Responder | 26 participants |
Secondary
Clinical Status
Compare the clinical efficacy at end of treatment visit of dalbavancin to the comparator regimen based on lesion size, local signs, temperature and receipt of non-study antibiotics
Time frame: End of Treatment Visit (Day 14-15)
Population: Clinical Evaluable Population based on certain inclusion/exclusion criteria, length of study therapy, concomitant antibacterials, concomitant surgical procedure and non-missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalbavancin | Clinical Status | Clinical Success | 214 participants |
| Dalbavancin | Clinical Status | Clinical Failure | 32 participants |
| Vancomycin +/- Oral Linezolid | Clinical Status | Clinical Success | 222 participants |
| Vancomycin +/- Oral Linezolid | Clinical Status | Clinical Failure | 21 participants |
Secondary
Clinical Status
Compare the clinical efficacy at the day 28 follow-up visit of dalbavancin to the comparator regimen based on lesion size, local signs, temperature and receipt of non-study antibiotics
Time frame: Follow-Up Visit (day 28)
Population: Clinical Evaluable Population based on certain inclusion/exclusion criteria, length of study therapy, concomitant antibacterials, concomitant surgical procedure and non-missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalbavancin | Clinical Status | Clinical Success | 212 participants |
| Dalbavancin | Clinical Status | Clinical Failure | 14 participants |
| Vancomycin +/- Oral Linezolid | Clinical Status | Clinical Success | 220 participants |
| Vancomycin +/- Oral Linezolid | Clinical Status | Clinical Failure | 9 participants |