1340. Concordance of Clinical Response at 48-72 hours after Initiation of Therapy and End of Treatment (EOT) in Patients with Acute Bacterial Skin and Skin Structure Infection (abSSSI) in the DISCOVER Studies
Session: Poster Abstract Session: Clinical Trials
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • Concordance_Poster_FINAL_IDSA.pdf (73.6 kB)
  • Background:

    Recent guidance from FDA recommends that the assessment timepoint for determination of non-inferiority in registrational abSSSI studies be made at 48-72 h after initiation of treatment.  Historically, timepoints for assessment of clinical response have typically been at the end of treatment (EOT) or thereafter, at days 14-28.  We performed an analysis of these two endpoints from data generated in the phase 3 DISCOVER program, which compared dalbavancin (DAL) to vancomycin/linezolid (V/L) for treatment of abSSSI.

    Methods:

    The two DISCOVER trials were randomized, double-blinded studies in which patients with skin infection lesions >75cm2 in area and either fever, WBC >12k cells/mm3 or bands >10% were randomized to receive either DAL  1g IV over 30 mins on D 1 followed by 500 mg IV on D 8 or V 1 gm or 15 mg/kg IV every 12 h (q12h) with an option to switch to L 600 mg po q12h after 3 days of therapy. Measurements obtained at 48-72 h recorded the cessation of spread of the lesion and absence of fever. Patients were not required to discontinue therapy based on these assessments. Clinical status was assessed programmatically based on the resolution of signs and symptoms of infection at EOT on D 14.

    Results:

    The majority (945/1046, 90.3%) of patients who responded favorably to treatment by 72 h were ultimately cured. Most (129/182, 70.9%) patients who were non-responders on D 3  were also subsequently cured. 72/1046 patients (6.9%) who were early responders were clinical failures at EOT while 50/182 (27.5%) early non-responders were clinical failures at EOT.

     

    Early Clinical Response (D3)

    Clinical Responder

    Clinical non-Responder

    Indeterminate

    Total

    Clinical Status at EOT (D14)

    n

    %

    n

    %

    n

    %

    Clinical Success

    945

    72.0

    129

    9.8

    53

    4.0

    1127 (85.9%)

    Clinical Failure

    72

    5.5

    50

    3.8

    10

    0.8

    132 (10.1%)

    Indeterminate

    29

    2.2

    3

    0.2

    21

    1.6

    53 (4.0%)

    Total

    1046 (79.7%)

    182 (13.9%)

    84 (6.4%)

    1312

    Conclusion:

    The majority of early responding patients were ultimately cured. Early non-responders were more likely to require a change in treatment. While the rigorous early response definition used for registrational purposes allows justification of a non-inferiority trial design, it does not capture all the factors clinicians consider in deciding whether to continue or discontinue therapy at that time.

    Michael Dunne, MD, Durata Therapeutics, Inc., Branford, CT, Sailaja Puttagunta, MD, Durata Therapeutics, Branford, CT, Mark Wilcox, MD, Microbiology, Leeds Teaching Hospitals and University of Leeds, Leeds, United Kingdom, George Talbot, MD, Talbot Advisors LLC, Anna Maria, FL and Helen Boucher, MD, FIDSA, Tufts New Engl Med Ctr, Boston, MA

    Disclosures:

    M. Dunne, Durata Therapeutics: Employee and Shareholder, Salary

    S. Puttagunta, Durata Therapeutics: Employee, Salary

    M. Wilcox, Actelion: Consultant and Research Contractor, Consulting fee and Research support
    Astellas: Consultant and Research Contractor, Consulting fee and Research support
    Biomerieux: Research Contractor, Research support
    Cubist: Consultant and Research Contractor, Consulting fee and Research support
    Pfizer: Consultant, Research Contractor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium
    Summit: Research Contractor, Research support
    The Medcine Company: Research Contractor, Research support
    Astra Zeneca: Consultant, Consulting fee
    Bayer: Consultant, Consulting fee
    Durata: Consultant, Consulting fee
    J&J: Consultant, Consulting fee
    Merck: Consultant, Consulting fee
    Nabriva: Consultant, Consulting fee
    Novacta: Consultant, Consulting fee
    Novartis: Consultant, Consulting fee
    Optimer: Consultant, Consulting fee
    Sanofi-Pasteur: Consultant, Consulting fee
    The Medicine Company: Consultant, Consulting fee
    VH Squared: Consultant, Consulting fee
    Viropharma: Consultant, Consulting fee

    G. Talbot, Durata Therapeutics: Scientific Advisor and Shareholder, Consulting fee

    H. Boucher, Durata Therapeutics: Consultant, Consulting fee

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