Back to resultsDaptomycin Versus Vancomycin in Participants With Skin Infections Due to MRSA (DAPHEOR1006)
Primary Purpose
Staphylococcal Skin Infections
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Daptomycin
Vancomycin
Sponsored by
About this trial
This is an interventional treatment trial for Staphylococcal Skin Infections focused on measuring Complicated Skin and Skin Structure Infections (cSSSI), Methicillin-resistant Staphylococcus aureus (MRSA), Daptomycin, Vancomycin, Antibiotics
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
- 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
- Are suspected or documented to be caused by MRSA
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Daptomycin
Vancomycin
Arm 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.
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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT01419184
First Posted
August 16, 2011
Last Updated
August 6, 2018
Sponsor
Cubist Pharmaceuticals LLC
1. Study Identification
Unique Protocol Identification Number
NCT01419184
Brief Title
Daptomycin Versus Vancomycin in Participants With Skin Infections Due to MRSA
Acronym
DAPHEOR1006
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
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
September 9, 2011 (Actual)
Primary Completion Date
September 1, 2012 (Actual)
Study Completion Date
October 5, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cubist Pharmaceuticals LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Staphylococcal Skin Infections
Keywords
Complicated Skin and Skin Structure Infections (cSSSI), Methicillin-resistant Staphylococcus aureus (MRSA), Daptomycin, Vancomycin, Antibiotics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
250 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Daptomycin
Arm Type
Experimental
Arm 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.
Arm Title
Vancomycin
Arm Type
Active Comparator
Arm 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
Intervention Type
Drug
Intervention Name(s)
Daptomycin
Other Intervention Name(s)
Cubicin
Intervention Type
Drug
Intervention Name(s)
Vancomycin
Primary Outcome Measure Information:
Title
Infection-Related Hospital Length of Stay
Description
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.
Time Frame
Baseline (Day 0) through the End of Hospital Stay (up to Day 14)
Secondary Outcome Measure Information:
Title
Mean Change From Baseline to Hospital Discharge in Pain According to the Brief Pain Inventory-Short Form (BPI-SF)
Description
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.
Time Frame
Baseline (Day 0), End of Hospital Stay (up to Day 14)
Title
Mean Change From Baseline to Hospital Discharge in Participant-reported Health-related Quality of Life (HRQoL)
Description
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.
Time Frame
Baseline (Day 0), End of Hospital Stay (up to Day 14)
Title
Participant Global Impression of Improvement (PGI-I) at Hospital Discharge
Description
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.
Time Frame
End of Hospital Stay (up to Day 14)
Title
30-day cSSSI-related Hospital Readmission Rates
Description
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.
Time Frame
End of Hospital Stay (up to Day 14) through 30 days post hospital discharge
Title
cSSSI-related Medical Resource Utilization and Costs
Description
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.
Time Frame
Baseline (Day 0) through 30 days post hospital discharge
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
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
Are suspected or documented to be caused by MRSA
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cubist Pharmaceuticals Medical Monitor Medical Monitor
Organizational Affiliation
Cubist Pharmaceuticals LLC
Official's Role
Study Director
Facility Information:
City
Mobile
State/Province
Alabama
Country
United States
City
Chula Vista
State/Province
California
Country
United States
City
Escondido
State/Province
California
Country
United States
City
La Mesa
State/Province
California
Country
United States
City
Oceanside
State/Province
California
Country
United States
City
Augusta
State/Province
Georgia
Country
United States
City
Decatur
State/Province
Georgia
Country
United States
City
Waterloo
State/Province
Iowa
Country
United States
City
Topeka
State/Province
Kansas
Country
United States
City
Louisville
State/Province
Kentucky
Country
United States
City
New Orleans
State/Province
Louisiana
Country
United States
City
Worcester
State/Province
Massachusetts
Country
United States
City
Detroit
State/Province
Michigan
Country
United States
City
Royal Oak
State/Province
Michigan
Country
United States
City
Minneapolis
State/Province
Minnesota
Country
United States
City
Las Vegas
State/Province
Nevada
Country
United States
City
Albany
State/Province
New York
Country
United States
City
Bronx
State/Province
New York
Country
United States
City
East Meadow
State/Province
New York
Country
United States
City
Mineola
State/Province
New York
Country
United States
City
Winston-Salem
State/Province
North Carolina
Country
United States
City
Columbus
State/Province
Ohio
Country
United States
City
Toledo
State/Province
Ohio
Country
United States
City
Rapid City
State/Province
South Dakota
Country
United States
City
Austin
State/Province
Texas
Country
United States
City
Ponce
Country
Puerto Rico
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
26547411
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.
Results Reference
derived
Learn more about this trial
Daptomycin Versus Vancomycin in Participants With Skin Infections Due to MRSA
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