Oritavancin Versus IV Vancomycin for the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infection

Phase 3

Completed

Conditions: Wound Infection
Abscess
Systemic Inflammation
Cellulitis

Interventions: Drug: Single-Dose IV Oritavancin Diphosphate
Drug: IV Vancomycin

Registration Number: NCT01252732

Lead Sponsor: Melinta Therapeutics, Inc.

Brief Summary: The purpose of this Phase 3 trial is to evaluate the efficacy, safety, and tolerability of oritavancin in ABSSSIs, including those caused by MRSA and to evaluate the potential economic benefit of oritavancin administered as a single 1200 mg IV dose.

Detailed Description: This is a Phase 3, multicenter, randomized, double-blind, parallel, comparative efficacy and safety study of single-dose IV oritavancin/IV placebo versus IV vancomycin for 7 to 10 days in adults with acute bacterial skin and skin structure infection (ABSSSI) suspected or proven to be caused by Gram-positive pathogens. Approximately 960 patients will be randomized at 100 centers globally.

In addition, this study will characterize the PK and PK/PD properties of a single 1200 mg IV dose of oritavancin and evaluate the potential health economic benefits offered by this dosing strategy.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1019

Inclusion Criteria

Subjects may be included in the study if they meet all of the following inclusion criteria:

Males or females ≥18 years old
Diagnosis of ABSSSI suspected or confirmed to be caused by a Gram-positive pathogen requiring at least 5 days of IV therapy
An ABSSSI includes one of the following infections Wound infections, Cellulitis/erysipelas, Major cutaneous abscess
ABSSSI must present with at least 2 signs and symptoms
Able to give informed consent and willing to comply with all required study procedures

Exclusion Criteria

Subjects will be excluded from the study if any of the following exclusion criteria apply prior to randomization:

Prior systemic or topical antibacterial therapy with activity against suspected or proven Gram-positive pathogens within the preceding 14 days
- The causative Gram-positive pathogen(s) isolated from the ABSSSI site is resistant in vitro to the antibacterial(s) that was administered with documented clinical progression, or
- Documented failure to previous ABSSSI antibiotic therapy is available. Documentation of treatment failure must be recorded
- Patient received a single dose of a short acting antibacterial therapy three or more days before randomization
Infections associated with, or in close proximity to, a prosthetic device
Severe sepsis or refractory shock
Known or suspected bacteremia at time of screening
ABSSSI due to or associated with any of the following:
- Infections suspected or documented to be caused by Gram-negative pathogens -- Wound infections (surgical or traumatic) and abscesses with only Gram-negative pathogens
- Diabetic foot infections
- Concomitant infection at another site not including a secondary ABSSSI lesion
- Infected burns
- A primary infection secondary to a pre-existing skin disease with associated inflammatory changes
- Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease
- Any evolving necrotizing process gangrene or infection suspected or proven to be caused by Clostridium species
- Infections known to be caused by a Gram-positive organism with a vancomycin MIC >2 μg/mL or clinically failing prior therapy with glycopeptides
- Catheter site infections
Allergy or intolerance to aztreonam or metronidazole in a patient with suspected or proven polymicrobial wound infection involving Gram-negative and/or anaerobic bacteria
Currently receiving chronic systemic immunosuppressive therapy
AIDS with CD4 count < 200 cells/mm3
Neutropenia
Significant or life-threatening condition that would confound or interfere with the assessment of the ABSSSI
Women who are pregnant or nursing
History of immune-related hypersensitivity reaction to glycopeptides
Patients that require anticoagulant monitoring with an aPTT
Contraindication to vancomycin
Patients unwilling to forego blood and/or blood product donation
Treatment with investigational medicinal product within 30 days before enrollment and for the duration of the study
Investigational device present, or removed <30 days before enrollment, or presence of device-related infection
Patients unlikely to adhere to the protocol, comply with study drug administration, or complete the clinical study
Severe hepatic disease
Presence of hyperuricemia
Unwilling to refrain from chronic use of any medication with antipyretic properties

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Single-Dose IV Oritavancin Diphosphate	Single-Dose IV Oritavancin Diphosphate	-
IV Vancomycin	IV Vancomycin	-

Primary Outcome Measures

Name	Time	Method
Early Clinical Response	48-72 hours after the initation of study therapy	Clinical response at the ECE visit (48-72 hours following initiation of study drug administration). Early clinical response was defined as a composite outcome based on, cessation of spreading or reduction in the size of baseline lesion, absence of fever and no rescue antibiotic medication.

Secondary Outcome Measures

Name	Time	Method
>= 20% Reduction in Lesion Area	48-72 hours after the initation of study therapy	Clinical response at the ECE visit (48-72 hours following initiation of study drug administration) based on changes in ABSSSI lesion size measurements from baseline.
Investigator Assessed Clinical Cure at Post Therapy Evaluation (Key Secondary Endpoint)	7 to 14 days after end of therapy	Compared the clinical efficacy at the Post Therapy Evaluation of Oritavancin and Vancomycin based on the Investigator examination of the signs and symptoms of the primary ABSSSI; Investigator assessment of clinical cure is complete or nearly complete resolution of baseline signs and symptoms of the primary infection such that no further treatment with antibiotics is needed