Clinical trial NCT02582203: Clinical and Economic Outcomes of Ceftaroline Fosamil for ABSSSI Documented or at Risk of MRSA
Official title: Clinical and Economic Outcomes of Ceftaroline Fosamil for the Treatment of Acute Bacterial Skin and Skin Structure Infections Documented or at Risk of Methicillin-Resistant S. Aureus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Skin Diseases, Infectious
Staphylococcal Skin Infections
Keywords: Ceftaroline fosamil
Vancomycin
Acute bacterial skin and skin structure infections
Methicillin-resistant S. aureus
Lead sponsor: Wayne State University
Sponsor class: OTHER
Collaborators: name: Henry Ford Hospital
name: St. John Providence Health System
name: Detroit Medical Center
name: Forest Laboratories
First posted: 2015-10-21
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Early Clinical Response
timeFrame: 48 to 72 hours after initiation of study drug
Secondary outcomes:
measure: Overall Clinical Response
timeFrame: End or therapy or patient discharge [Up to 60 days]
measure: Length of stay
timeFrame: During hospitalization [Up to 60 days]
Other outcomes:
measure: Adverse Events
timeFrame: During treatment with study drug [Up to 60 days]
Locations:
city: Detroit
country: United States
facility: Detroit Medical Center
state: Michigan
city: Detroit
country: United States
facility: St. John Hospital and Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
Study officials:
affiliation: Wayne State University
name: Michael Rybak, PharmD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Claeys KC, Zasowski EJ, Trinh TD, Casapao AM, Pogue JM, Bhatia N, Mynatt RP, Wilson SS, Arthur C, Welch R, Sherwin R, Hafeez W, Levine DP, Kaye KS, Delgado G, Giuliano CA, Takla R, Rieck C, Johnson LB, Murray KP, Gordon J, Reyes K, Hartman P, Davis SL, Rybak MJ. Open-Label Randomized Trial of Early Clinical Outcomes of Ceftaroline Fosamil Versus Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections at Risk of Methicillin-Resistant Staphylococcus aureus. Infect Dis Ther. 2019 Jun;8(2):199-208. doi: 10.1007/s40121-019-0242-5. Epub 2019 Mar 27.