Retapamulin Versus Placebo in Secondarily-Infected Traumatic Lesions (SITL)

Phase 3

Completed

Conditions: Skin Infections, Bacterial

Interventions: Drug: Retapamulin Ointment, 1%
Drug: Placebo ointment

Registration Number: NCT00684177

Lead Sponsor: GlaxoSmithKline

Brief Summary: The purpose of Study TOC110977 is to demonstrate clinical superiority of Retapamulin ointment, 1%, over placebo in patients with secondarily-infected traumatic lesions, which includes secondarily-infected lacerations, abrasions and sutured wounds. Subjects 2 months of age and older will be treated with topical retapamulin or placebo ointment twice daily for 5 days. The primary endpoint of this study is the clinical response at follow-up (Day 12-14; 7-9 days after the end of therapy) in the intent-to-treat clinical population.

Detailed Description: This is a prospective, multicenter, double-blind, placebo-controlled parallel group study in subjects aged 2 months and older with SITL, including secondarily-infected lacerations, sutured wounds or abrasions. A laceration or sutured wound cannot exceed 10 cm in length with surrounding erythema not extending more than 2 cm from the edge of the lesion. Abrasions cannot exceed 100 cm2 in total area, or up to a maximum of 2% total body surface area for subjects \<18 years of age, with surrounding erythema not extending more than 2 cm from the edge of the abrasion.

There are four study visits occurring over a 12-14 day period. At the Baseline visit (Visit 1, Day 1), subjects will be randomized to receive retapamulin or placebo ointment in a 2:1 (retapamulin:placebo) ratio. The 2:1 randomization is included to minimize the number of subjects exposed to treatment with placebo. Both active treatment and placebo will be dosed topically twice daily (BID) for 5 days. All subjects will receive a telephone call from the investigator or appropriate designee appointed by the investigator on Day 2. The subject will be interviewed to determine if there is any evidence of worsening infection. Subjects who are thought to be worsening will be instructed to come in to the clinic for an assessment. Subjects will be monitored and clinically evaluated at the On-therapy (Days 3-4), End of Therapy (Days 7-9), and Follow-up (Days 12-14) visits.

Randomization will be center-based and performed using an appropriate Interactive Voice Response System (IVRS), an automated telephone system. The block size will remain confidential.

Subjects are considered to have completed the study if they meet all inclusion/exclusion criteria, are considered compliant with study medication, and attend all study visits as defined by the protocol.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 508

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Retapamulin Ointment, 1%	Retapamulin Ointment, 1%	-
Placebo Ointment	Placebo ointment	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Clinical Success and Failure at Follow-up (7-9 Days Post Therapy) for the Primary Efficacy Population	Days 12-14	"Clinical Success" at follow-up was defined as "Resolution of clinically meaningful signs and symptoms of infection recorded at baseline including a pus/exudate Skin Infection Rating Scale (SIRS) score of "0". Clinical response at follow-up was classified as "Clinical Failure" for all other cases. The SIRS consists of seven items (pus/exudates, crusting, erythema/inflammation, tissue warmth, tissue edema, itching and pain). Each item has a score ranging from 0 to 6 (0=absent, 6=severe). The SIRS total score was calculated as the sum of the scores of all 7 SIRS items.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Therapeutic Success and Failure at Follow-up (7-9 Days Post Therapy)	Follow-up (Days 12-14)	"Therapeutic Success (Succ)" was referred to as both "Clinical Succ" and "Microbiological (Micro) Succ" at Follow-up. "Clinical Succ" was the "Resolution of baseline signs/symptoms of infection with a pus score of "0." A participant was "Micro Succ" if the micro outcome for all baseline pathogens (bps) belonged to "Eradication" (elimination of bps), "Presumed Eradication" (clinical outcome is success; no culturable material), or "Colonization" (new pathogen is identified at end of therapy in participants who are resolved/improved). All other combinations were deemed "Therapeutic Failures."
Number of Participants With Clinical Success and Failure at Follow-up (7-9 Days Post Therapy) for the Intent-to-Treat Bacteriology (ITTB) Subset of the Primary Efficacy Population	Days 12-14	"Clinical Success" at follow-up was defined as "Resolution of clinically meaningful signs and symptoms of infection recorded at baseline including a pus/exudate Skin Infection Rating Scale (SIRS) score of "0". Clinical response at follow-up was classified as "Clinical Failure" for all other cases. The SIRS consists of seven items (pus/exudates, crusting, erythema/inflammation, tissue warmth, tissue edema, itching and pain). Each item has a score ranging from 0 to 6 (0=absent, 6=severe). The SIRS total score was calculated as the sum of the scores of all 7 SIRS items.
Number of Participants With Microbiological Success and Failure at Follow-up (7-9 Days Post Therapy)	Days 12-14	The "by pathogen" microbiological outcome was determined by comparing the baseline culture results to those at follow-up. The "by subject" microbiological response was "Microbiological Success" if the microbiological outcomes for all baseline pathogens (bps) belong to "Eradication" (elimination of bps), "Presumed Eradication" (clinical outcome was success; no culture was obtained due to lack of culturable material), or "Colonization" (previously unidentified pathogen is identified at end of therapy in participant who is resolved/improved); otherwise, response was "Microbiological Failure".
Number of Baseline Pathogens With the Indicated Microbiological Outcome at End of Therapy (2-4 Days Post Therapy)	Days 7-9	The "by pathogen" microbiological outcome was determined by comparing the baseline culture results to those at follow-up. The results presented below pooled all baseline pathogens (bps). Eradication: elimination of bps. Presumed Eradication: clinical outcome was success; no culture was obtained due to lack of culturable material. Presumed Improvement: clinical outcome was improvement such that no culture was obtained due to lack of culturable material. Persistence: bps still present. Presumed persistence: clinical failure and no culture was obtained.
Number of Participants With the Indicated Clinical Outcome at End of Therapy (2-4 Days Post Therapy)	Days 7-9	Clinical outcome is determined by the investigator based on signs and symptoms (S/S) at the end of therapy evaluation. The 4 clincal outcome categories are: clinical success, resolution of clinically meaningful S/S of infection recorded at baseline (BL), including a pus/exudates score of 0; clinical improvement, improvement of S/S of infection recorded at BL to such an extent that no further antimicrobial therapy is necessary; clinical failure, insufficient improvement of deterioration of S/S of infection recorded at BL such that additional antibiotic therapy is required; unable to determine.