910. Cessation of Spread of Lesion and Absence of Fever at 72 hours in Complicated Skin and Skin Structure Infection (cSSSI): Reanalysis of the Combined ASSIST Phase III Studies Comparing Iclaprim (ICL) and Linezolid (LZD)
Session: Poster Abstract Session: Clinical Trials
Friday, October 9, 2015
Room: Poster Hall
Posters
  • 910_IDWPOSTER.pdf (808.3 kB)
  • Background: ICL, a new generation diaminopyrimidine compound, is a dihydrofolate reductase inhibitor antibiotic in clinical development. The efficacy of ICL was tested in two identical randomized double-blind Phase III clinical trials comparing ICL to LZD in the treatment of patients with cSSSI.  The endpoint of cessation of spread of lesion and absence of fever was evaluated at a 72 hour visit using the combined data.

    Methods: Patients with cSSSI were treated for 10–14 days with IV ICL 0.8 mg/kg q 12 hours or IV linezolid (LZD) 600 mg q 12 hours.  Outcomes were reanalyzed applying cessation of spread of lesion/erythema as well as absence of fever at 72 hours in intent-to-treat (ITT) populations.

    Results:

    The total ITT population comprised 991 (ICL: 500; LZD: 491).  The distribution of infection types was very similar in both treatment groups and encompassed wound infections (30%), cellulitis (38%), major abscesses (26%), infected ulcers (11%) and first- or second-degree burns (10%). Staphylococcus aureus (591 isolates) accounted for 69.9% of all Gram-positive pathogens, of which 39.9% were methicillin-resistant (MRSA). 73% had a fever >38°C, and 94% had an erythema score of moderate or severe.  The Table shows high lesion response and fever resolution at 72 hours in the ITT populations: 73.6% (95% CI = 69.5–77.4%) for ICL and 72.5% (95% CI = 68.3–76.4%) for LZD recipients (difference 1.1%, 95% CI = -4.5% to 6.6%).

     

    ASSIST-1

    ASSIST-2

    Combined

     

     

    ICL

    LZD

    ICL

    LZD

    ICL

    LZD

    N

    249

    248

    251

    243

    500

    491

    Responder

    184 (73.9%)

    177 (71.4%)

    184 (73.3%)

    179 (73.7%)

    368 (73.6%)

    356 (72.5%)

    95% CI

    68.0%-79.2%

    65.3%-76.9%

    67.4%-78.7%

    67.7%-79.1%

    69.5%-77.4%

    68.3%-76.4%

    Difference

    2.5%

    -0.4%

    1.1%

    95% CI

    -5.6% - 10.6%

    -8.4% - 7.7%

    -4.5% - 6.6%

    Conclusion: At 72h, ICL achieved a high rate of cessation of spread of erythema and fever resolution in patients with cSSSI. This was comparable to that seen with LZD. ICL could be an important new therapeutic option for treatment of cSSSI, especially those caused by MRSA. Pivotal clinical trials are warranted to evaluate ICL for the indication of acute bacterial skin and skin structure infections.

    David Huang, MD, PhD, Motif BioSciences, New York, NY, Mark Wilcox, MD, Microbiology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, Matthew Dryden, MD, Royal Hampshire County Hospital, Winchester, United Kingdom, Paul Hadvary, PhD, Formerly Arpida AG, CH, Reinach, Switzerland and Ralph Corey, MD, Duke University Medical Center, Durham, NC

    Disclosures:

    D. Huang, Motif BioSciences: Employee , Salary

    M. Wilcox, Motif BioSciences: Consultant , Scientific Advisor and Shareholder , Consulting fee
    Pfizer: Consultant , Scientific Advisor and Speaker's Bureau , Consulting fee and Speaker honorarium
    Durata: Consultant and Scientific Advisor , Consulting fee
    Cerexa: Consultant and Scientific Advisor , Consulting fee
    Paratek: Consultant and Scientific Advisor , Consulting fee
    Nabriva: Consultant and Scientific Advisor , Consulting fee

    M. Dryden, None

    P. Hadvary, None

    R. Corey, Motif BioSciences: Consultant , Consulting fee

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