Objective.

—To compare the safety and efficacy of topical 1% penciclovir cream with vehicle control cream (placebo) for the treatment of a recurrent episode of herpes simplex labialis (cold sores) in immunocompetent patients.

Design.

—Randomized, double-blind, placebo-controlled, patient-initiated, 2-armed, parallel clinical trial. Patients were prospectively dispensed study medication, and treatment was self-initiated by the patient within 1 hour of the first sign or symptom of a recurrence.

Setting.

—A total of 31 ambulatory clinics in the United States in a variety of settings, including private practices, public health facilities, and universities.

Patients.

—Otherwise healthy individuals with a history of frequent episodes of herpes simplex labialis. A total of 2209 patients were enrolled and given study medication, and 1573 initiated treatment for a recurrence.

Interventions.

—Topical 1% penciclovir cream or vehicle control cream. Subjects applied treatment every 2 hours while awake for 4 consecutive days.

Main Outcome Measures.

—Lesion healing was the primary efficacy variable. Secondary end points included time to loss of lesion pain and time to cessation of viral shedding.

Results.

—Healing of classical lesions (vesicles, ulcers, and/or crusts) was 0.7 day faster for penciclovir-treated patients compared with those who received vehicle control cream (median, 4.8 days vs 5.5 days; hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.18-1.49;P<.001). Pain (median, 3.5 days vs 4.1 days; HR, 1.22; 95% CI, 1.09-1.36;P<.001) and lesion virus shedding (median, 3 days vs 3 days; HR, 1.35; 95% CI, 1.10-1.64;P=.003) also resolved more quickly for penciclovir-treated patients compared with patients who applied the vehicle control. The efficacy of penciclovir cream was apparent when therapy was initiated early (prodrome or erythema lesion stage) and when initiated late (papule or vesicle stage). The incidence of adverse events was comparable between penciclovir and placebo groups.

Conclusions.

—Penciclovir cream is the first treatment to clearly demonstrate an impact on the course of recurrent herpes labialis in immunocompetent patients. Efficacy was seen in all clinical and laboratory measures of the disease (lesion healing, pain resolution, and cessation of viral shedding). Faster healing and pain resolution occurred both among patients who first applied penciclovir cream in the prodrome and erythema stages and among those who started treatment in the papule and vesicle lesion stages.

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