Skin Diseases, Infectious, Staphylococcal Skin Infections
Conditions
Keywords
Ceftaroline fosamil, Vancomycin, Acute bacterial skin and skin structure infections, Methicillin-resistant S. aureus
Brief summary
The proposed study is a prospective, open-label, randomized, multi-center trial of ceftaroline versus vancomycin for the treatment of ABSSSI in patients documented or at risk for MRSA. Patients admitted to the Detroit Medical Center, Henry Ford Hospital, or St. John Medical Center in Detroit Michigan with a documented ABSSSI between April 2012 and November 2015 will be evaluated for inclusion. Patients must present with at least 3 of the following local signs/symptoms: pain, tenderness, swelling erythema, warmth, drainage/discharge, induration, and lymph node swelling/tenderness. Patients will be randomized 1:1 ceftaroline or vancomycin with optional anaerobic and/or Gram-negative coverage. The assignment of study drug will follow a randomized list that was previously generated via a computerized random mix block generator (nQuery Advisor® 7.0) and available at each of the study sites. Patients will be randomized to ceftaroline intravenously at 600 mg infused over 1 hour every 12 hours for patients with normal renal function. Patients randomized to vancomycin will receive the standard 15 mg/kg dose based on total body weight infused over 1 hour q 12 hour, dose and interval adjusted based on creatinine clearance and via institution-specific pharmacy protocol to target serum trough concentrations of 10-20 mg/L within the first 72 hours. Outcomes measured in the Clinically Evaluable patient population include day two or three size reduction (percentage) and clinical response at end of therapy or discharge.
Interventions
DRUGCeftaroline
DRUGVancomycin
Sponsors
Henry Ford Hospital
St. John Providence Health System
Detroit Medical Center
Forest Laboratories
Wayne State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
Yes
Inclusion criteria
* Acute bacterial skin and skin structure infection (cellulitis, major abscess, surgical site infection) * Presence of MRSA or documented risk factors for MRSA (prior antibiotic use 60 days, prior hospital exposure 180 days, skin ulcers, central venous catheter) * Anticipating no less than two days of hospital admission * Signed informed consent
Exclusion criteria
* Gas gangrene/progressive necrotizing infections * Osteomyelitis * Infections due to Gram-negative pathogens or other Gram-positive pathogens if S. aureus or Streptococcus is not present * Pathogens known at the study entry to be resistant to ceftaroline or vancomycin * Anticipated to require non-study antibiotic active against S. aureus for another reason * Treatment for the current episode of ABSSSI for \> 24 hours with another intravenous anti-MRSA antibiotic * Surgical (I & D) as definitive/curative treatment * Presence of prosthetic hardware or invasive devices suspected to be the source of infection but cannot be removed * Life expectancy \< 2 months * Open burn wound \> 30% total body surface area * Pregnant or nursing mothers * Known allergic reaction to vancomycin or ceftaroline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Early Clinical Response | 48 to 72 hours after initiation of study drug | Reduction of lesion size from baseline of at least 20% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Clinical Response | End or therapy or patient discharge [Up to 60 days] | Cure: pretreatment signs and symptoms are improved or resolved and no additional antibiotic therapy is necessary * Improved: pretreatment signs and symptoms are improved and additional antibiotic therapy is necessary * Failure: Persistent, worsening, or new/recurrent signs and symptoms, antibiotics needed \> 14 days, or the need for a change in antibiotic therapy |
| Length of stay | During hospitalization [Up to 60 days] | Total duration of hospitalization |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | During treatment with study drug [Up to 60 days] | Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. |
Countries
United States
Outcome results
None listed