Study to Compare Efficacy and Safety of Daptomycin in Elderly Patients With Complicated Skin and Soft Tissue Infections

An Open Label, Multi-center, Randomized, Comparative Phase IIIb Study to Compare Efficacy and Safety of Intravenous (i.v.) Daptomycin With That of Semi-Synthetic Penicillins (SSPs) or Vancomycin in the Treatment of Elderly Patients (Aged ≥ 65 Years) With Complicated Skin and Soft Tissue Infections (cSSTI)

The purpose of this study is to provide data documenting the efficacy of daptomycin in elderly patients aged ≥ 65 years with complicated Skin and Soft Tissue Infections.

Study Overview

• Status: Completed
• Conditions: Infections
• Intervention / Treatment: Drug: Daptomycin; Drug: Vancomycin or Semi-Synthetic Penicillins (SSPs)

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • Novartis Investigative Site
  • Vienna, Austria
    • Novartis Investigative Site
• Germany
  • Bochum, Germany
    • Novartis Investigative Site
  • Essen, Germany
    • Novartis Investigative Site
  • Homburg, Germany
    • Novartis Investigative Site
  • Magdeburg, Germany
    • Novartis Investigative Site
  • Mannheim, Germany
    • Novartis Investigative Site
  • Muenster, Germany
    • Novartis Investigative Site
  • Tuebingen, Germany
    • Novartis Investigative Site
• Italy
  • Pisa, Italy
    • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation
    • Novartis Investigative Site (1)
  • Novosibirsk, Russian Federation
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation
    • Novartis Investigative Site (2)
  • Yaroslavi, Russian Federation
    • Novartis Investigative Site
• Spain
  • Madrid, Spain
    • Novartis Investigative Site (1)
  • Santander, Spain
    • Novartis Investigative Site
  • Seville, Spain
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

Patients 65 years or older with infection of sufficient severity to require in-patient hospitalization, with parenteral antimicrobial therapy for at least 96 hours.

Patients who have a diagnosis of Gram-positive complicated Skin and Soft Tissue Infections (cSSTIs) with or without bacteremia:

• Wound infections,
• Major abscesses with or without recognized preceding trauma, that require antibiotic therapy in addition to surgical incision and drainage,
• Severe carbunculosis,
• Infected ulcers (except patients with multiple infected ulcers) associated with: diabetes, vascular insufficiency, pressure (i.e., decubitus ulcers).

Exclusion criteria:

Conditions requiring surgery that in and of itself would cure the infection or remove the infected site (e.g., amputation).

Minor or superficial skin infections (e.g., furuncles, simple abscesses, acne, impetigo).

Cellulitis, including erysipelas, not associated with complicating factors. However, patients with cellulitis associated with more serious infection (e.g., surgical wound, diabetic ulcer, deep tissue) can be enrolled (proportion of these patients will be limited to 30%).

Infections for which outcome is difficult to assess:

• Perirectal abscess,
• Hidradenitis suppurativa,
• Gangrene,
• Infected human or animal bites,
• Multiple infected ulcers at distant sites,
• Infected burns (only third degree burn wound or wound area of more than 10 cm diameter),
• Conditions requiring emergency surgery including necrotizing fasciitis.

Medical conditions:

• History of significant allergy or intolerance to Vancomycin or Daptomycin. Hypersensitivity to SSPs penicillins is not an exclusion criterion,
• Concomitant clinically suspected or confirmed other site of infection or disorder at study entry that may interfere with the evaluation in this protocol,
• Infections associated with a permanent prosthetic device that will not be removed within 24 hours after enrolment,
• Known or suspected HIV infection with a CD4+ T-cell count < 500/μL (HIV testing is not required),
• Severe hepatic disease (Child-Pugh Class C) or ALT and/or AST > 5 times ULN and/ or total bilirubin > 2 times ULN at screening,
• Calculated creatinine clearance by the Cockcroft-Gault equation using actual body weight < 30 mL/min or any type of dialysis,
• Treatment with any investigational agent or device within 30 days of study drug administration.

Exclusion criteria related to medications:

• Previous systemic antibacterial therapy for the treatment of Gram-positive complicated skin and soft tissue infections for more than 24 hours within 48 hours prior to the day of first infusion of study drug unless:
• The previous antibacterial therapy was administered for 3 or more calendar days with either worsening or no improvement in the clinical signs and symptoms of cSSTIs, and was not Vancomycin or SSPs.

Other protocol-defined inclusion/exclusion criteria applied.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Daptomycin; Patients with bacteremia: Daptomycin 6 mg/Kg intravenous once daily for at least 5 days and up to 28 days. Patients without bacteremia: Daptomycin 4 mg/Kg intravenous once daily for at least 5 days and up to 14 days.	Drug: Daptomycin; Patients with bacteremia: Daptomycin 6 mg/Kg intravenous once daily for at least 5 days and up to 28 days. Patients without bacteremia: Daptomycin 4 mg/Kg intravenous once daily for at least 5 days and up to 14 days.
ACTIVE_COMPARATOR: Vancomycin or Semi-Synthetic Penicillins (SSPs); Patients with bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 4 hours for at least 5 days and up to 28 days. Patients without bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 6 hours for at least 5 days and up to 14 days.	Drug: Vancomycin or Semi-Synthetic Penicillins (SSPs); Patients with bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 4 hours for at least 5 days and up to 28 days. Patients without bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 6 hours for at least 5 days and up to 14 days.; Other Names: Oxacillin,; Cloxacillin,; Flucloxacillin,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Clinical Success at the Test-Of-Cure (TOC) Visit	Success: Clinically significant signs and symptoms associated with the skin infection present at the pre-treatment infection site resolved (cure), or improved without need of further antibacterial therapy. Failure: Persistence or progression of signs and symptoms or development of new clinical signs and symptoms at the infection site, or concomitant antibacterial therapy with activity against isolated organisms, or treatment duration longer than pre-specified, or switch back to intravenous therapy due to relapse, or requirement of a major surgical procedure as adjunct or follow-up therapy.	Baseline and 7 to 14 days after end of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Microbiological Response at Test-of-Cure (TOC) Visit	Microbiological Success: All infecting Gram-positive pathogens isolated at baseline were eradicated or presumed to be eradicated at the Test-of-Cure (TOC) evaluation and a super infecting pathogen was not isolated either prior to or at the TOC evaluation. Microbiological Failure: Persistence or relapse / re-infection of one or more infecting Gram-positive pathogens or isolation of a super infecting pathogen prior to or at the TOC evaluation.	Baseline and 7 to 14 days after end of therapy
Duration of Treatment (Intravenous)	Duration of treatment is the interval from first to last intravenous (i.v.) administration. It was preferable that a patient complete the whole antibiotic treatment with the randomized i.v. study drug only. Duration of treatment in patients with bacteremia could be extended up to 28 days.	Up to 28 days
Duration of Treatment (Intravenous and Oral)	Duration of treatment is the interval from first to last intravenous (i.v.) or to last oral administration if patients switched to an oral antibiotic therapy. It was preferable that a patient complete the whole antibiotic treatment with the randomized i.v. study drug only. Duration of treatment in patients with bacteremia could be extended up to 28 days.	Up to 28 days
Number of Patients With Adverse Events, Serious Adverse Events and Death		Continuously from baseline up to 28 days after end of antibiotic treatment.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Arbeit RD, Maki D, Tally FP, Campanaro E, Eisenstein BI; Daptomycin 98-01 and 99-01 Investigators. The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clin Infect Dis. 2004 Jun 15;38(12):1673-81. doi: 10.1086/420818. Epub 2004 May 20.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (ACTUAL): March 1, 2011
• Study Completion (ACTUAL): March 1, 2011

Study Registration Dates

• First Submitted: February 18, 2010
• First Submitted That Met QC Criteria: August 18, 2010
• First Posted (ESTIMATE): August 19, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): July 13, 2012
• Last Update Submitted That Met QC Criteria: July 9, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Elderly; Daptomycin; Skin infection; Gram positive; Complicated skin and soft tissue infections
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Soft Tissue Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Daptomycin; Floxacillin; Cloxacillin; Penicillins; Oxacillin
• Other Study ID Numbers: CCBC134A2404; 2009-014391-22 (EUDRACT_NUMBER)