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.
Brief Title
Daptomycin Versus Vancomycin in Participants With Skin Infections Due to MRSA
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Staphylococcal Skin Infections
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
* ≥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
Inclusion 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
* ≥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
Gender
All
Gender Based
false
Keywords
Complicated Skin and Skin Structure Infections (cSSSI)
Methicillin-resistant Staphylococcus aureus (MRSA)
Daptomycin
Vancomycin
Antibiotics
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01419184
Org Class
Industry
Org Full Name
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Org Study Id
3009-015
Overall Status
Completed
Phases
Phase 4
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome 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.
Outcome Measure
Infection-Related Hospital Length of Stay
Outcome Time Frame
Baseline (Day 0) through the End of Hospital Stay (up to Day 14)
Secondary Ids
Secondary Id
DAP-HEOR-10-06
Secondary Outcomes
Outcome 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.
Outcome Time Frame
Baseline (Day 0), End of Hospital Stay (up to Day 14)
Outcome Measure
Mean Change From Baseline to Hospital Discharge in Pain According to the Brief Pain Inventory-Short Form (BPI-SF)
Outcome 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.
Outcome Time Frame
Baseline (Day 0), End of Hospital Stay (up to Day 14)
Outcome Measure
Mean Change From Baseline to Hospital Discharge in Participant-reported Health-related Quality of Life (HRQoL)
Outcome 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.
Outcome Time Frame
End of Hospital Stay (up to Day 14)
Outcome Measure
Participant Global Impression of Improvement (PGI-I) at Hospital Discharge
Outcome 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.
Outcome Time Frame
End of Hospital Stay (up to Day 14) through 30 days post hospital discharge
Outcome Measure
30-day cSSSI-related Hospital Readmission Rates
Outcome 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.
Outcome Time Frame
Baseline (Day 0) through 30 days post hospital discharge
Outcome Measure
cSSSI-related Medical Resource Utilization and Costs
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Paul Riska
Investigator Email
priska@montefiore.org
Investigator Phone
718-020-6494