Efficacy and Safety of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections

Study Overview
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Brief Summary
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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 proved gram-positive bacterial skin or skin structure infections.

Official Title
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A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Dalbavancin to a Comparator Regimen (Vancomycin and Linezolid) for the Treatment of Acute Bacterial Skin and Skin Structure Infections

Conditions
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Abscess, Wound Infection, Surgical Site Infection, Cellulitis

Intervention / Treatment
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* Drug: IV Dalbavancin
* Drug: Vancomycin/Linezolid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients 18 - 85 years of age. Signed and dated informed consent document. Major abscess, surgical site infection, traumatic wound infection or cellulitis suspected or confirmed to be caused by Gram-positive bacteria. At least two (2) local signs and symptoms of ABSSSI and at least one (1) systemic sign of infection. Requires a minimum of 3 days of IV therapy. Patient willing and able to comply with study procedures. Exclusion Criteria: Patients presenting with any of the following: A contra-indication to any required study drug. Pregnant or nursing females. Sustained shock. Participation in another study of an investigational drug or device within 30 days. 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. Infection due to a dalbavancin or vancomycin-resistant organism. Evidence of meningitis, necrotizing fasciitis, gas gangrene, gangrene, septic arthritis, osteomyelitis, and/or endovascular infection. Exclusively gram-negative bacterial or a fungal ABSSSI. Venous catheter infection. Infection of a diabetic foot ulcer or a decubitus ulcer. Device-related infections. Gram-negative bacteremia. Infected burns. Infected limb with critical ischemia. Superficial/simple skin and skin structure infections. Concomitant condition requiring non-study antibacterial therapy. ABSSSI requiring therapy for longer than 14 days. Adjunctive therapy with hyperbaric oxygen. More than 2 surgical interventions for ABSSSI anticipated. Chronic inflammatory condition precluding assessment of clinical response. Absolute neutrophil count < 500 cells/mm3. Human immunodeficiency virus (HIV) infection with a CD4 cell count < 200 cells/mm3. Recent bone marrow transplant, > 20 mg prednisolone per day (or equivalent) or receiving immunosuppressant drugs after organ transplantation. Regular, chronic antipyretic use in patients unable to modify during the first three days of study drug therapy. Life expectancy less than 3 months. Conditions that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results. Prior participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vancomycin with possible switch to oral linezolid<br> | Drug: Vancomycin/Linezolid<br>* IV Vancomycin (1 gram Q 12 hours or 15mg/Kg Q 12 hours) with optional switch to oral linezolid (600 mg every 12 hours). Total duration of therapy is 10-14 days<br>|
| Experimental: Dalbavancin<br> | Drug: IV Dalbavancin<br>* IV Dalbavancin 1000 mg on Day 1 and 500 mg on Day 8<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | After 48-72 hours of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 other therapy | End of Treatment Visit (Day 14-15) | 
| >= 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 | 48-72 hours after the initiation of study therapy | 
| Clinical Status | Compare the clinical efficacy at the short term follow-up visit of dalbavancin to the comparator regimen based on lesion size, local signs temperature and receipt of other therapy | Follow-Up Visit (day 28) |