Clinical and Economic Outcomes of Ceftaroline Fosamil for ABSSSI Documented or at Risk of MRSA

NCT ID: NCT02582203

Last Updated: 2016-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 174 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2016-05-31

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.

Conditions

Skin Diseases, Infectious; Staphylococcal Skin Infections

Keywords

Ceftaroline fosamil; Vancomycin; Acute bacterial skin and skin structure infections; Methicillin-resistant S. aureus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ceftaroline

600 mg IV (over 1 hour) every 12 hours for renal function \> 50 mL/min, adjusted for renal function based on package insert for no more than 14 days.

Group Type: ACTIVE_COMPARATOR

Ceftaroline

Intervention Type: DRUG

Vancomycin

Dosed by institutional pharmacy protocol to reach goal trough level of 10 - 20 mg/L steady state concentration for no more than 14 days.

Group Type: ACTIVE_COMPARATOR

Vancomycin

Intervention Type: DRUG

Interventions

Ceftaroline

Intervention Type: DRUG

Vancomycin

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Henry Ford Hospital

OTHER

Sponsor Role: collaborator

St. John Providence Health System

OTHER

Sponsor Role: collaborator

Detroit Medical Center

OTHER

Sponsor Role: collaborator

Forest Laboratories

INDUSTRY

Sponsor Role: collaborator

Wayne State University

OTHER

Sponsor Role: lead

Responsible Party

Michael J. Rybak

Director, Anti-Infective Research Laboratory

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Rybak, PharmD, MPH

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Locations

Detroit Medical Center

Detroit, Michigan, United States

St. John Hospital and Medical Center

Detroit, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 30915685 (View on PubMed)

Other Identifiers

1111010324

Identifier Type: -

Identifier Source: org_study_id