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

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)

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.

Study Overview

• Status: Completed
• Conditions: Staphylococcal Skin Infections
• Intervention / Treatment: Drug: Vancomycin; Drug: Daptomycin

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.

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 4

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico
• United States
  • Alabama
    • Mobile, Alabama, United States
  • California
    • Chula Vista, California, United States
    • Escondido, California, United States
    • La Mesa, California, United States
    • Oceanside, California, United States
  • Georgia
    • Augusta, Georgia, United States
    • Decatur, Georgia, United States
  • Iowa
    • Waterloo, Iowa, United States
  • Kansas
    • Topeka, Kansas, United States
  • Kentucky
    • Louisville, Kentucky, United States
  • Louisiana
    • New Orleans, Louisiana, United States
  • Massachusetts
    • Worcester, Massachusetts, United States
  • Michigan
    • Detroit, Michigan, United States
    • Royal Oak, Michigan, United States
  • Minnesota
    • Minneapolis, Minnesota, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New York
    • Albany, New York, United States
    • Bronx, New York, United States
    • East Meadow, New York, United States
    • Mineola, New York, United States
  • North Carolina
    • Winston-Salem, North Carolina, United States
  • Ohio
    • Columbus, Ohio, United States
    • Toledo, Ohio, United States
  • South Dakota
    • Rapid City, South Dakota, United States
  • Texas
    • Austin, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daptomycin; 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.	Drug: Daptomycin; Other Names: Cubicin
Active Comparator: Vancomycin; 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	Drug: Vancomycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infection-Related Hospital Length of Stay	Infection Related Hospital Length of Stay (IRLOS) is defined as the number of hours of hospitalization associated with antibiotic treatment of the complicated skin and skin structure infections (cSSSI) beginning at initiation of study-antibiotic administration and ending at discontinuation of all antibiotic therapy for cSSSI or at hospital discharge (whichever occurred first). This included continued hospitalization for treatment of adverse events resulting from use of the study antibiotic or subsequent antimicrobial therapy. The mean number of hours for each treatment group is presented.	Baseline (Day 0) through the End of Hospital Stay (up to Day 14)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline to Hospital Discharge in Pain According to the Brief Pain Inventory-Short Form (BPI-SF)	Pain was measured as the amount of pain experienced "right now" by the participant using an 11-point numerical rating scale adapted from Brief Pain Inventory-Short Form (BPI-SF). Participants were asked to rate pain in his or her skin infection from 0 to 10, where 0 is no pain and 10 is pain as bad as he or she could imagine. Change from baseline to hospital discharge is presented; a negative value represents a decrease in pain.	Baseline (Day 0), End of Hospital Stay (up to Day 14)
Mean Change From Baseline to Hospital Discharge in Participant-reported Health-related Quality of Life (HRQoL)	Health-related quality of life (HRQoL) was measured using the EuroQol-5 Dimensions, 5 Level (EQ-5D-5L) multi-attribute questionnaire. The 5 dimensions measured were: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant's health state was expressed by a descriptive profile of a 5 digit number. The EQ-5D health states were converted into a single summary index (from 0 to 1, with 0 representing death, to 1 representing perfect health) by applying weights to each of the levels in each dimension. Change from baseline to hospital discharge is presented; positive values represent an increase in health utility.	Baseline (Day 0), End of Hospital Stay (up to Day 14)
Participant Global Impression of Improvement (PGI-I) at Hospital Discharge	PGI-I assessments of improvement were measured by asking participants: How is your skin infection today compared to how it was yesterday? Scores were calculated based on response to the single item, where 1 = improved a lot; 2 = improved moderately; 3 = improved a little; 4 = no change; 5 = worsened a little; 6 = worsened moderately; 7 = worsened a lot. Mean PGI-I scores are presented at hospital discharge; lower values represent greater improvement.	End of Hospital Stay (up to Day 14)
30-day cSSSI-related Hospital Readmission Rates	Hospital readmission rates were defined as readmission to an inpatient hospital facility within 30 days of hospital discharge for management of cSSSI relapse or treatment of adverse events related to cSSSI treatment. It did not include all-cause readmissions (for completeness, all-cause readmissions are reported in the descriptive tables). Participants were asked if they had been readmitted to the hospital since their discharge and whether the admission was specifically for their skin infection. The number of participants who were re-hospitalized for skin infection or side effects due to skin infection medication within 30 days since the initial hospital discharge (Day 14) is presented.	End of Hospital Stay (up to Day 14) through 30 days post hospital discharge
cSSSI-related Medical Resource Utilization and Costs	Direct medical costs were based on utilization of health resources. Unit cost data were obtained from sources external to the trial and assigned to corresponding medical resource utilization observed within the trial to estimate costs of care. cSSSI-related costs were reported from a societal perspective, and further broken down into a health care system perspective. The health care system perspective includes hospital and outpatient costs. The societal perspective includes the health care system perspective plus participant and caregiver time loss from work and participant and caregiver out-of-pocket expenses. Total cost (including both total inpatient and total post-discharge costs) per participant is presented.	Baseline (Day 0) through 30 days post hospital discharge

Collaborators and Investigators

• Sponsor: Cubist Pharmaceuticals LLC
• Investigators: Study Director: Cubist Pharmaceuticals Medical Monitor Medical Monitor, Cubist Pharmaceuticals LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): October 5, 2012

Study Registration Dates

• First Submitted: August 16, 2011
• First Submitted That Met QC Criteria: August 17, 2011
• First Posted (Estimate): August 18, 2011

Study Record Updates

• Last Update Posted (Actual): September 5, 2018
• Last Update Submitted That Met QC Criteria: August 6, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Vancomycin; Antibiotics; Daptomycin; Methicillin-resistant Staphylococcus aureus (MRSA); Complicated Skin and Skin Structure Infections (cSSSI)
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Inflammation; Disease Attributes; Connective Tissue Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Staphylococcal Infections; Suppuration; Skin Diseases, Bacterial; Infections; Communicable Diseases; Cellulitis; Skin Diseases, Infectious; Staphylococcal Skin Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Daptomycin
• Other Study ID Numbers: 3009-015; DAP-HEOR-10-06 (Other Identifier: Cubist Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf