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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00684177
First received: May 22, 2008
Last updated: August 23, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Secondarily-infected Abrasions
Secondarily-infected Lacerations
Secondarily-infected Sutured Wounds
Secondarily-infected Traumatic Lesions
Skin Infections, Bacterial
Drug: Retapamulin Ointment, 1%
Drug: Placebo ointment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Multicenter, Placebo-controlled, Phase III Superiority Study to Assess the Safety and Efficacy of Topical Retapamulin Ointment, 1%, Versus Placebo Ointment Applied Twice Daily for 5 Days in the Treatment of Adult and Pediatric Subjects With SITL

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With Clinical Success and Failure at Follow-up (7-9 Days Post Therapy) for the Primary Efficacy Population [ Time Frame: Days 12-14 ] [ Designated as safety issue: No ]
    "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:
  • 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 [ Time Frame: Days 12-14 ] [ Designated as safety issue: No ]
    "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) [ Time Frame: Days 12-14 ] [ Designated as safety issue: No ]
    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 Participants With the Indicated Clinical Outcome at End of Therapy (2-4 Days Post Therapy) [ Time Frame: Days 7-9 ] [ Designated as safety issue: No ]
    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.

  • Number of Baseline Pathogens With the Indicated Microbiological Outcome at End of Therapy (2-4 Days Post Therapy) [ Time Frame: Days 7-9 ] [ Designated as safety issue: No ]
    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 Therapeutic Success and Failure at Follow-up (7-9 Days Post Therapy) [ Time Frame: Follow-up (Days 12-14) ] [ Designated as safety issue: No ]
    "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."


Enrollment: 508
Study Start Date: May 2008
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Retapamulin Ointment, 1% Drug: Retapamulin Ointment, 1%
Provided as approximately 10 grams of an off-white smooth ointment in collapsible aluminum tubes with reverse taper puncture tip caps.
Other Names:
  • Retapamulin Ointment
  • 1%
Placebo Comparator: Placebo Ointment Drug: Placebo ointment
Provided as approximately 10 grams of an off-white smooth ointment in collapsible aluminum tubes with reverse taper puncture tip caps.

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.

  Eligibility

Ages Eligible for Study:   2 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • subject is aged 2 months or older
  • subject has secondarily-infected traumatic lesion (laceration, sutured wound or abrasion)
  • negative urine pregnancy test
  • subject has total skin infection rating scale score of at least 8, including pus/exudate score of at least 3
  • subject and/or parent/legal guardian is willing and able to comply with protocol
  • subject or parent/legal guardian has given written informed consent or assent as applicable

Exclusion criteria:

  • previous hypersensitivity to pleuromutilin
  • secondarily-infected animal/human bite or puncture wound
  • subject has an abscess
  • chronic ulcerative lesion
  • underlying skin disease
  • systemic signs and symptoms of infection
  • infection not appropriately treated with topical antibiotic
  • infection requires surgical intervention prior to or during study
  • subject received systemic antibacterial or steroid, or topical therapeutic agent within 24 hours of entry into study
  • serious underlying disease
  • subject pregnant, breast feeding or planning a pregnancy, or unacceptable method of contraception
  • other investigational drug within 30 days of study entry
  • subject previously enrolled in this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00684177

  Show 54 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00684177     History of Changes
Other Study ID Numbers: TOC110977
Study First Received: May 22, 2008
Results First Received: June 3, 2010
Last Updated: August 23, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
infection
retapamulin
secondarily-infected traumatic lesions
placebo

Additional relevant MeSH terms:
Bacterial Infections
Infection
Lacerations
Skin Diseases, Infectious
Skin Diseases
Wounds and Injuries

ClinicalTrials.gov processed this record on October 30, 2014