The Safety and Efficacy of Topical Retapamulin Ointment Versus Placebo Ointment in the Treatment of Secondarily Infected Traumatic Lesions

Tomayko, John F.; Li, Gang; Breton, John; Scangarella-Oman, Nicole; Dalessandro, Marybeth; Martin, Michael

doi:10.1097/01.asw.0000427922.12498.c4

Cited by 7 publications

(8 citation statements)

References 18 publications

(24 reference statements)

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“…The final selection of publications included 4 placebo-controlled uSSTI trials (35)(36)(37)(38), 12 linezolid trials (39-50), 3 ceftaroline trials (51-53), 1 retrospective ceftaroline secondary analysis (54), and 2 nonantibacterial treatment trials of UV light for erysipelas (23,24) (Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

“…The four trials as proxy for placebo included 234 subjects with a range of uncomplicated infections reported as impetigo, folliculitis, SITL, and pyoderma (Table 1). Publication dates were from 1974 to 2013, three of the trials enrolled a subset of subjects Ͻ18 years of age, and one publication required certified translation from French to English (35)(36)(37)(38). Each trial reported a TOC clinical treatment response; none reported an early clinical treatment response.…”

Section: Methodsmentioning

confidence: 99%

“…The four proxy for placebo uSSTI trials reported TOC clinical treatment response rates ranging from 8% to 66% (Table 2) (35)(36)(37)(38). Clinical and methodological heterogeneity was evident for lesion size, infection type, and timing of the TOC assessment (Table 3).…”

Section: Iii) Nonantibacterial Treatment Trials (Search C)mentioning

confidence: 99%

“…Clinical and methodological heterogeneity was evident for lesion size, infection type, and timing of the TOC assessment (Table 3). For the meta-analysis, the trial that restricted enrollment to subjects with SITL was excluded (35), resulting in a pooled proxy for placebo TOC clinical treatment response rate of 31.0% (95% CI, 6.2% to 55.9%); the variance across trials (I 2 ϭ 90.6%, P Ͻ 0.0001) was high ( Fig. 2a) (36)(37)(38).…”

Section: Iii) Nonantibacterial Treatment Trials (Search C)mentioning

confidence: 99%

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Systematic Review and Meta-Analysis To Estimate Antibacterial Treatment Effect in Acute Bacterial Skin and Skin Structure Infection

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Mitrani-Gold

et al. 2015

Antimicrob Agents Chemother

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A systematic literature review and meta-analysis were conducted to estimate the antibacterial treatment effect for linezolid and ceftaroline to inform on the design of acute bacterial skin and skin structure infection (ABSSSI) noninferiority trials. The primary endpoints included an early clinical treatment response (ECTR) defined as cessation of lesion spread at 48 to 72 h postrandomization and the test-of-cure (TOC) response defined as total resolution of the infection at 7 to 14 days posttreatment. The systematic review identified no placebo-controlled trials in ABSSSI, 4 placebo-controlled trials in uncomplicated skin and soft tissue infection as a proxy for placebo in ABSSSI, 12 linezolid trials in ABSSSI, 3 ceftaroline trials in ABSSSI, and 2 trials for nonantibacterial treatment. The ECTR rates at 48 to 72 h and corresponding 95% confidence intervals (CI) were 78.7% (95% CI, 61.1 to 96.3%) for linezolid, 74.0% (95% CI, 69.7 to 78.3%) for ceftaroline, and 59.0% (95% CI, 52.8 to 65.3%) for nonantibacterial treatment. The early clinical treatment effect could not be estimated, given no available placebo or proxy for placebo data for this endpoint. Clinical, methodological, and statistical heterogeneity influenced the selection of trials for the meta-analysis of the TOC treatment effect estimation. The pooled estimates of the TOC treatment response were 31.0% (95% CI, 6.2 to 55.9%) for the proxy for placebo, 88.1% (95% CI, 81.0 to 95.1%) for linezolid, and 86.1% (95% CI, 83.7 to 88.6%) for ceftaroline. The TOC clinical treatment effect estimation was 25.1% for linezolid and 27.8% for ceftaroline. The antibacterial treatment effect estimation at TOC will inform on the design and analysis of future noninferiority ABSSSI clinical trials. Over the past decade, robust clinical, scientific, and regulatory debate has emerged for initiatives to improve the design, execution, and analysis of antibacterial clinical trials (1-4). New trials for acute bacterial skin and skin structure infections (ABSSSI), previously referred to as complicated skin and skin structure infections (cSSTI), remain important, given the rise in incidence of methicillin-resistant Staphylococcus aureus infections and reports of treatment failure (5-8). Per guidance from the U.S. Food and Drug Administration (FDA), patient eligibility for enrollment in ABSSSI trials should be restricted to those with erysipelas, cellulitis, major cutaneous abscesses, and wound infections having a minimal lesion surface area involvement of 75 cm 2 (9). For trial endpoints, the traditional test-of-cure (TOC) endpoint, with the treatment success defined as total resolution of the infection at 7 to 14 days posttreatment, remains aligned with the European regulatory guidance, yet the treatment success for the primary efficacy endpoint aligned with the FDA guidance is defined as cessation of lesion spread after 48 to 72 h of treatment (9-11). Revisions to the enrollment and endpoint criteria in recent regulatory guidance for ABSSSI trials necessitate reevaluation of the...

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