Efficacy and Safety of Daptomycin Versus Vancomycin or Teicoplanin for Treatment of Complicated Skin and Soft Tissue Infections

• ClinicalTrials.gov Identifier: NCT00430937
• Recruitment Status: Terminated
• First Posted: February 2, 2007
• Results First Posted: January 5, 2011
• Last Update Posted: July 16, 2012
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

This study evaluated the efficacy and safety of daptomycin compared to vancomycin or teicoplanin for the treatment of complicated skin and soft tissue infections

Condition or disease	Intervention/treatment	Phase
Skin Diseases, Infectious; Soft Tissue Infections	Drug: Daptomycin; Drug: Vancomycin; Drug: Teicoplanin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 194 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Assessor-Blind Study to Evaluate Efficacy and Safety of Daptomycin Versus Vancomycin or Teicoplanin for Treatment of Complicated Skin and Soft Tissue Infections (cSSTI)
• Study Start Date: April 2006
• Actual Primary Completion Date: March 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Daptomycin; 4 mg/kg intravenous (i.v.) once daily	Drug: Daptomycin; 4 mg/kg intravenous once daily; Other Name: Cubicin
Active Comparator: Pooled Comparator	Drug: Vancomycin; 1 g intravenous twice daily; Other Name: Vancocin; Drug: Teicoplanin; 400 mg intravenous once daily following a loading dose of 400 mg administered at 0, 12, 24 hours on day one.; Other Name: Targocid

Outcome Measures

Primary Outcome Measures :

1. Clinical Success as Measured by Comparing the Participants Signs and Symptoms at the "Test of Cure" (TOC) Visit to Those Recorded at Study Baseline in the Clinically Evaluable Population. [ Time Frame: Baseline to TOC Visit (7-14 days after end of treatment) up to 4 weeks ]

   Success: Total resolution of clinically significant signs and symptoms of the infection site (cure) or improvement to such a level that no further antibacterial therapy was required (improvement).

   Failure: Persistence or progression of signs and symptoms after at least 3 days of study therapy, or development of new signs and symptoms at the infection site, or concomitant or additional antibacterial therapy with documented activity against isolated organisms, or a treatment duration greater than 14 days, or requirement of a major surgical procedure as adjunct or follow-up therapy.

Secondary Outcome Measures :

1. Microbiological Efficacy Measured by the Number of Participants Achieving Bacteriological Eradication of Gram-positive Baseline Pathogens at the TOC Visit. [ Time Frame: Baseline to TOC Visit (7-14 days after end of treatment) up to 4 weeks ]

   Microbiological Success: All infecting Gram-positive pathogens isolated at baseline were eradicated at the TOC evaluation and a superinfecting pathogen was not isolated either prior to or at the TOC evaluation.

   Microbiological Failure: Persistence of one or more infecting Gram-positive pathogens or isolation of a superinfecting pathogen prior to or at the TOC evaluation.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

• Subjects with a diagnosis of cSSTI
• Infection known or suspected (based on Gram's stain) to be due, at least partially, to Gram-positive bacteria.
• Hospitalised subjects with clinical evidence of at least one of the following:I infected ulcers , major abscess. deep or extensive cellulitis, post-surgical / post-traumatic wound infection
• Presence of at least two of the following: drainage and/or discharge from the infection site, redness, swelling and/or hardened skin, heat and/or localised warmth, pain and/or tenderness to touch, presence of pus.

Exclusion criteria:

• cSSTIs of the following categories:

  • Infected burns,
  • Severely impaired arterial blood supply (such that the likelihood of amputation of the infected anatomical site is likely),
  • Decubitus ulcers,
  • Infected diabetic foot ulcers associated with osteomyelitis,
  • Infected human or animal bites, superficial infections or abscesses in an anatomic site, such as the rectal area, where the risk of anaerobic or Gram-negative pathogen involvement is high (e.g. perirectal abscess),
  • Necrotising fasciitis or gangrene,
  • cSSTI expected to require more than 14 days of intravenous antimicrobial therapy,
  • Skin and/or skin structure infection that can be treated by surgery alone,
  • Infections associated with a permanent prosthetic device that will not be removed within 2 days of study randomisation
• Subjects with documented bacteraemia at Baseline or those with shock or hypotension
• Concomitant clinically suspected or confirmed other site of infection or disorder at study entry that may interfere with the evaluations in this protocol
• Treatment with vancomycin or teicoplanin within the past 48 hours, unless administered for less than 24 hours.
• Subjects admitted to the hospital for conditions associated with rhabdomyolysis or those with an infection due to an organism known prior to study entry to be resistant to daptomycin, vancomycin or teicoplanin.
• Previously diagnosed disease of immune function. Human Immunodeficiency Virus (HIV) infected subjects without Acquired Immune Deficiency Syndrome (AIDS) may be enrolled.
• Subjects receiving oral steroids or receiving immunosuppressant drugs after organ transplant.
• Absence of purulent material for initial culture and Gram's stain. Subjects with cellulitis may be enrolled in the absence of purulent material, provided that infection with a Gram-positive organism is suspected.
• Subjects who have received more than 48 hours of any systemic antibiotic or topical antibiotic at the infection site with activity against Gram-positive pathogens, unless there is clinical evidence of treatment failure OR documented resistance in the identified Gram-positive pathogen to the previous antibiotic therapy.
• cSSTI suspected or documented as being due exclusively to Gram-negative or anaerobic organisms based on epidemiology or on direct examination of a Gram-stained specimen.
• Subjects diagnosed with pneumonia or those with severe renal impairment or hepatic disease
• Previous history of hearing loss. Other protocol defined inclusion/exclusion criteria may apply.

Contacts and Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00430937
• Other Study ID Numbers: CCBC134A2402
• First Posted: February 2, 2007
• Results First Posted: January 5, 2011
• Last Update Posted: July 16, 2012
• Last Verified: July 2012

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Complicated Skin and Soft Tissue Infections. Daptomycin, Vancomycin, Teicoplanin; Complicated skin and soft tissue infections

Additional relevant MeSH terms:

Infection; Communicable Diseases; Soft Tissue Infections; Skin Diseases, Infectious; Skin Diseases; Vancomycin; Daptomycin; Teicoplanin; Anti-Bacterial Agents; Anti-Infective Agents