Clinical trial NCT01252732: Oritavancin Versus IV Vancomycin for the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infection
Official title: A Multicenter, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of Single-Dose IV Oritavancin Versus IV Vancomycin for the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infection (SOLO II)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Wound Infection
Abscess
Systemic Inflammation
Cellulitis
Keywords: ABSSSI
Skin Infection
Abscess
Lead sponsor: Melinta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2010-12-03
Enrollment: 1019
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: 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.

Eligibility criteria: Inclusion Criteria:

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

1. Males or females ≥18 years old
2. Diagnosis of ABSSSI suspected or confirmed to be caused by a Gram-positive pathogen requiring at least 5 days of IV therapy
3. An ABSSSI includes one of the following infections Wound infections, Cellulitis/erysipelas, Major cutaneous abscess
4. ABSSSI must present with at least 2 signs and symptoms
5. 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:

1. 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
2. Infections associated with, or in close proximity to, a prosthetic device
3. Severe sepsis or refractory shock
4. Known or suspected bacteremia at time of screening
5. 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
6. Allergy or intolerance to aztreonam or metronidazole in a patient with suspected or proven polymicrobial wound infection involving Gram-negative and/or anaerobic bacteria
7. Currently receiving chronic systemic immunosuppressive therapy
8. AIDS with CD4 count \< 200 cells/mm3
9. Neutropenia
10. Significant or life-threatening condition that would confound or interfere with the assessment of the ABSSSI
11. Women who are pregnant or nursing
12. History of immune-related hypersensitivity reaction to glycopeptides
13. Patients that require anticoagulant monitoring with an aPTT
14. Contraindication to vancomycin
15. Patients unwilling to forego blood and/or blood product donation
16. Treatment with investigational medicinal product within 30 days before enrollment and for the duration of the study
17. Investigational device present, or removed \<30 days before enrollment, or presence of device-related infection
18. Patients unlikely to adhere to the protocol, comply with study drug administration, or complete the clinical study
19. Severe hepatic disease
20. Presence of hyperuricemia
21. Unwilling to refrain from chronic use of any medication with antipyretic properties

Primary outcomes:
measure: Early Clinical Response
timeFrame: 48-72 hours after the initation of study therapy
Secondary outcomes:
measure: Investigator Assessed Clinical Cure at Post Therapy Evaluation (Key Secondary Endpoint)
timeFrame: 7 to 14 days after end of therapy
measure: >= 20% Reduction in Lesion Area
timeFrame: 48-72 hours after the initation of study therapy
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: Sharp Grossmont Hospital
state: California
Study officials:
affiliation: Duke Clinical Research Institute
name: G. Ralph Corey, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Corey GR, Loutit J, Moeck G, Wikler M, Dudley MN, O'Riordan W; SOLO I and SOLO II investigators. Single Intravenous Dose of Oritavancin for Treatment of Acute Skin and Skin Structure Infections Caused by Gram-Positive Bacteria: Summary of Safety Analysis from the Phase 3 SOLO Studies. Antimicrob Agents Chemother. 2018 Mar 27;62(4):e01919-17. doi: 10.1128/AAC.01919-17. Print 2018 Apr.
citation: Deck DH, Jordan JM, Holland TL, Fan W, Wikler MA, Sulham KA, Ralph Corey G. Single-Dose Oritavancin Treatment of Acute Bacterial Skin and Skin Structure Infections: SOLO Trial Efficacy by Eron Severity and Management Setting. Infect Dis Ther. 2016 Sep;5(3):353-61. doi: 10.1007/s40121-016-0119-9. Epub 2016 Jul 1.
citation: Corey GR, Good S, Jiang H, Moeck G, Wikler M, Green S, Manos P, Keech R, Singh R, Heller B, Bubnova N, O'Riordan W; SOLO II Investigators. Single-dose oritavancin versus 7-10 days of vancomycin in the treatment of gram-positive acute bacterial skin and skin structure infections: the SOLO II noninferiority study. Clin Infect Dis. 2015 Jan 15;60(2):254-62. doi: 10.1093/cid/ciu778. Epub 2014 Oct 6.