Clinical trial NCT01419184: Daptomycin Versus Vancomycin in Participants With Skin Infections Due to MRSA
Official title: A Randomized Study to Evaluate Comparative Effectiveness, Inpatient Resource Utilization, and Cost of Daptomycin vs. Vancomycin in the Treatment of Patients With Complicated Skin and Skin Structure Infections Due to Suspected or Documented Methicillin-resistant Staphylococcus Aureus (MRSA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Staphylococcal Skin Infections
Keywords: Complicated Skin and Skin Structure Infections (cSSSI)
Methicillin-resistant Staphylococcus aureus (MRSA)
Daptomycin
Vancomycin
Antibiotics
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2011-08-18
Enrollment: 250
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: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Infection-Related Hospital Length of Stay
timeFrame: Baseline (Day 0) through the End of Hospital Stay (up to Day 14)
Secondary outcomes:
measure: Mean Change From Baseline to Hospital Discharge in Pain According to the Brief Pain Inventory-Short Form (BPI-SF)
timeFrame: Baseline (Day 0), End of Hospital Stay (up to Day 14)
measure: Mean Change From Baseline to Hospital Discharge in Participant-reported Health-related Quality of Life (HRQoL)
timeFrame: Baseline (Day 0), End of Hospital Stay (up to Day 14)
measure: Participant Global Impression of Improvement (PGI-I) at Hospital Discharge
timeFrame: End of Hospital Stay (up to Day 14)
measure: 30-day cSSSI-related Hospital Readmission Rates
timeFrame: End of Hospital Stay (up to Day 14) through 30 days post hospital discharge
measure: cSSSI-related Medical Resource Utilization and Costs
timeFrame: Baseline (Day 0) through 30 days post hospital discharge
Other outcomes:
Locations:
city: Mobile
country: United States
state: Alabama
city: Chula Vista
country: United States
state: California
city: Escondido
country: United States
state: California
city: La Mesa
country: United States
state: California
city: Oceanside
country: United States
state: California
city: Augusta
country: United States
state: Georgia
city: Decatur
country: United States
state: Georgia
city: Waterloo
country: United States
state: Iowa
city: Topeka
country: United States
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Worcester
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Royal Oak
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Las Vegas
country: United States
state: Nevada
city: Albany
country: United States
state: New York
city: Bronx
country: United States
state: New York
city: East Meadow
country: United States
state: New York
city: Mineola
country: United States
state: New York
city: Winston-Salem
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Rapid City
country: United States
state: South Dakota
city: Austin
country: United States
state: Texas
city: Ponce
country: Puerto Rico
Study officials:
affiliation: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
name: Cubist Pharmaceuticals Medical Monitor Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Kauf TL, McKinnon P, Corey GR, Bedolla J, Riska PF, Sims M, Jauregui-Peredo L, Friedman B, Hoehns JD, Mercier RC, Garcia-Diaz J, Brenneman SK, Ng D, Lodise T. An open-label, pragmatic, randomized controlled clinical trial to evaluate the comparative effectiveness of daptomycin versus vancomycin for the treatment of complicated skin and skin structure infection. BMC Infect Dis. 2015 Nov 7;15:503. doi: 10.1186/s12879-015-1261-9.