Daptomycin Versus Vancomycin in Participants With Skin Infections Due to MRSA (DAPHEOR1006)

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Status and phase: Completed; Phase 4

Conditions: Staphylococcal Skin Infections

Treatments: Drug: Vancomycin; Drug: Daptomycin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01419184

3009-015

DAP-HEOR-10-06 (Other Identifier)

Details and patient eligibility

About

This was a real-world, prospective, open-label, multicenter study in which participants were randomized (1:1) to receive intravenous (IV) vancomycin or IV daptomycin. The purpose of this study is to compare infection-related hospital length of stay, along with a number of participant-reported outcomes, between participants with complicated skin and soft tissue infection treated with daptomycin and vancomycin.

Full description

Eligible participants will be recruited within 24 hours of hospital admission for cSSSI due to suspected or documented Methicillin-resistant Staphylococcus Aureus (MRSA), and who are anticipated to require IV antibiotics effective against MRSA and at least 3 days of hospitalization for management of cSSSI. The primary objective is to compare infection-related hospital length of stay between participants treated with daptomycin and vancomycin. Secondary objectives were to compare participant reported outcomes (pain symptoms and Health Related Quality of Life), 30 day cSSSI-related hospital readmission rates, and cSSSI-related medical resource utilization and costs between participants treated with daptomycin and vancomycin.

Enrollment: 250 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ≥18 years of age

• Primary reason for hospitalization is skin and skin structure infection of a complicated nature (for example, cellulitis/erysipelas, major cutaneous abscess, or wound infection) that requires IV antibiotic treatment for an anticipated 3 to14 days and hospitalization for management

  1. Further defined as infections either involving deeper soft tissue or requiring significant surgical intervention or infections in which the participant has a significant underlying disease state that complicates the response to treatment
  2. Are suspected or documented to be caused by MRSA
  3. At least 3 of the following clinical signs and symptoms associated with the cSSSI:

  i. Pain; tenderness to palpation; ii. Elevated temperature (>37.5°Celsius [99.5° Farenheit] oral or >38° Celsius [100.2° Farenheit] rectal); iii. Elevated white blood count (WBC) >10,000/millimeters cubed (mm^3); iv. Swelling and/or induration; erythema; v. Purulent or seropurulent drainage or discharge

• Physician determination that vancomycin or daptomycin would be the initial treatment of choice for the cSSSI under study (or meets institutional criteria for use of vancomycin or daptomycin)

• Informed consent obtained and signed

• Less than 24 hours post hospital admission

Exclusion criteria

• Participants with known bacteremia, osteomyelitis, septic arthritis, or endocarditis
• Conditions where surgery (in and of itself) constitutes curative treatment of the infection (for example, amputation, incision and drainage)
• cSSSIs which can be managed with an oral antibiotic
• Participants where hospitalization is expected to be <48 hours
• Nosocomial infection
• Participants with necrotizing infections or concomitant gangrene
• Use of systemic antibacterial therapy for the infection for > 24 hours within 48 hours prior to the start of study drug unless (a) the infecting Gram-positive pathogen was resistant in vitro to the therapy or (b) the therapy was administered for 3 or more days with either worsening or no improvement in the infection
• Pathogens identified at study entry to be nonsusceptible to daptomycin or vancomycin
• Participants with neutropenia or compromised immune function (that is, severe neutropenia [absolute neutrophil count <500 cells per microliter (μL)] or is anticipated to develop severe neutropenia during the study period due to prior or planned therapy)
• Renal insufficiency (calculated creatinine clearance [CLcr] <30 milliliters per minute or on dialysis)
• Known to be allergic or intolerant to daptomycin or vancomycin
• Pregnant or nursing mothers
• Suspected implanted device or prosthetic as source of infection
• Is considered unlikely to comply with study procedures or to be available for follow-up contact

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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250 participants in 2 patient groups

Daptomycin

Experimental group

Description:

4 milligrams per kilogram (mg/kg) daptomycin administered intravenously (IV) once a day until end of antibiotic therapy for complicated skin and skin structure infections (cSSSI) or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.

Treatment:

Drug: Daptomycin

Vancomycin

Active Comparator group

Description:

Vancomycin was reconstituted per the manufacturer's instructions and was dosed per investigator's discretion and was administered IV until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occured first. Investigators treated participants according to their usual decision-making and discretion

Treatment:

Drug: Vancomycin