Clinical trial NCT00852540: Retapamulin Versus Linezolid in the Treatment of SITL and Impetigo Due to MRSA
Official title: A Randomized, Double-Blind, Double Dummy, Comparative, Multicenter Study to Assess the Safety and Efficacy of Topical Retapamulin Ointment, 1%, Versus Oral Linezolid in the Treatment of Secondarily-Infected Traumatic Lesions and Impetigo Due to Methicillin-Resistant Staphylococcus Aureus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Skin Infections, Bacterial
Keywords: impetigo
methicillin-resistant Staphylococcus aureus
linezolid
secondarily-infected traumatic lesion
uncomplicated skin infection
retapamulin
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2009-02-27
Enrollment: 410
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to provide further evidence of the clinical and bacteriological efficacy of retapamulin in the treatment of subjects with SITL or impetigo due to MRSA. Subjects aged 2 months and older will be treated with either topical retapamulin for 5 days or oral linezolid for 10 days. The primary endpoint is the clinical response at follow-up (7-9 days after the end of therapy) in subjects who have a MRSA infection at baseline. The primary population is the per-protocol MRSA population. It is anticipated that approximately 500 subjects may be enrolled in order to obtain approximately 105 subjects who have a baseline MRSA infection.

Detailed description: This is a prospective, randomized, double-blind, double dummy, multicenter, comparative study in subjects 2 months of age and older with SITL (including secondarily-infected lacerations, sutured wounds and abrasions) or impetigo (bullous and non-bullous) due to MRSA. 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. Subjects with impetigo can have up to 10 lesions and the infected lesion(s) must not be more than 100 cm2 in area (or up to a maximum of 2% total body surface area for subjects \<18 years of age), must not require surgical intervention and must be able to be appropriately treated with a topical antibiotic.

There are five study visits occurring over a 17-19 day period. At the baseline visit (Visit 1, day 1), subjects will be randomized to receive retapamulin (plus oral placebo) or linezolid (plus placebo ointment) in a 2:1 ratio. Retapamulin is applied twice daily for 5 days, and linezolid is dosed, depending on subject age, either twice or three times daily for 10 days. The on-therapy, end of therapy and follow-up visits are staggered due to the difference in duration of the treatment regimens. Subjects will be monitored and clinically evaluated at all postbaseline visits.

Randomization will be center-based and stratified by age (\<5 years, ≥5 to \<12 years, ≥12 years), 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 criteria: Inclusion Criteria:

* 2 months of age or older
* diagnosis of secondarily-infected traumatic lesion (SITL) or impetigo (bullous or non-bullous)
* negative urine pregnancy test (females of childbearing potential)
* total skin infection rating scale (SIRS) score of at least 8, which must include a pus/exudate score of at least 3
* subject or parent/legal guardian willing and able to comply with protocol
* written informed, dated consent, and written assent (if applicable)

Exclusion Criteria:

* previous hypersensitivity to pleuromutilins or oxazolidinones
* phenylketonuria or known hypersensitivity to aspartame
* secondarily-infected animal/human bite, or puncture wound
* abscess
* chronic ulcerative lesion
* underlying skin disease (eg, eczematous dermatitis) with secondary infection
* systemic signs and symptoms of infection
* skin infection not appropriate for treatment by a topical antibiotic (eg, extensive cellulitis, furunculosis)
* subject requires surgical intervention for infection prior to study or likely will during the study
* receipt of systemic antibacterial or steroid, or application of any topical therapeutic agent directly to wound within 24 hours of entry into the study
* subject currently receiving adrenergic agents
* subject currently receiving serotonergic agents
* history of pseudomembranous colitis
* known, pre-existing myelosuppression, history of myelosuppression with linezolid use, or receiving a medication that produces bone marrow suppression
* history of siezures
* history of severe renal failure and undergoing dialysis
* serious underlying disease that could be imminently life-threatening
* pregnant, breast feeding or planning a pregnancy, or not using accepted method of contraception (females of childbearing potential or \<1 year post-menopausal)
* use of another investigational drug within 30 days prior to entry into this study
* previously enrolled in this study
* fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency (for subjects \<12 years of age receiving linezolid suspension)

Primary outcomes:
measure: Number of Participants Achieving Clinical Response at Follow-up Who Had Methicillin-resistant Staphlococcus Aureus (MRSA) as a Baseline Pathogen
timeFrame: 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid
Secondary outcomes:
measure: Number of Participants Achieving Microbiological Response (MR) at Follow-up (FU) Who Had MRSA as a Baseline Pathogen (BP)
timeFrame: 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid
measure: Number of Participants With Clinical Response at Follow-up
timeFrame: 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid
measure: Number of Participants Who Achieved Microbiological Response (MR) at Follow-up (FU) Who Had a Baseline Pathogen (BP)
timeFrame: 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid
measure: Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen
timeFrame: 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid
measure: Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen
timeFrame: 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid
measure: Number of Participants With the Indicated Clinical Outcome at the End of Therapy
timeFrame: 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid
measure: Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy
timeFrame: 2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid
measure: Number of Participants With Therapeutic Response at Follow-up
timeFrame: 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid
measure: Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5
timeFrame: Visits 1 (Day 1), 2 (Day 3-4), 3 (Day 7-9), 4 (Day 12-14), and 5 (Day 17-19)
measure: Mean Wound Size at Visits 1, 2, 3, 4, and 5
timeFrame: Visits 1 (Day 1), 2 (Day 3-4), 3 (Day 7-9), 4 (Day 12-14), and 5 (Day 17-19)
Other outcomes:
Locations:
city: Anniston
country: United States
facility: GSK Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Bentonville
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Jonesboro
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Paragould
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Bakerfield
country: United States
facility: GSK Investigational Site
state: California
city: Bell Gardens
country: United States
facility: GSK Investigational Site
state: California
city: Huntington Beach
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Roseville
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Atlantis
country: United States
facility: GSK Investigational Site
state: Florida
city: Bay Pines
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Ft. Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Pensacola
country: United States
facility: GSK Investigational Site
state: Florida
city: St. Petersburg
country: United States
facility: GSK Investigational Site
state: Florida
city: Vero Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Columbus
country: United States
facility: GSK Investigational Site
state: Georgia
city: Macon
country: United States
facility: GSK Investigational Site
state: Georgia
city: Savannah
country: United States
facility: GSK Investigational Site
state: Georgia
city: Honolulu
country: United States
facility: GSK Investigational Site
state: Hawaii
city: Honolulu
country: United States
facility: GSK Investigational Site
state: Hawaii
city: South Bend
country: United States
facility: GSK Investigational Site
state: Indiana
city: Overland Park
country: United States
facility: GSK Investigational Site
state: Kansas
city: Louisville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: New Orleans
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Grand Blanc
country: United States
facility: GSK Investigational Site
state: Michigan
city: Jackson
country: United States
facility: GSK Investigational Site
state: Mississippi
city: Butte
country: United States
facility: GSK Investigational Site
state: Montana
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Brooklyn
country: United States
facility: GSK Investigational Site
state: New York
city: Carlisle
country: United States
facility: GSK Investigational Site
state: Ohio
city: Tulsa
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Corvallis
country: United States
facility: GSK Investigational Site
state: Oregon
city: Gresham
country: United States
facility: GSK Investigational Site
state: Oregon
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Hazleton
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Duncanville
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Layton
country: United States
facility: GSK Investigational Site
state: Utah
city: Charlottesville
country: United States
facility: GSK Investigational Site
state: Virginia
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Tanus T, Scangarella-Oman NE, Dalessandro M, Li G, Breton JJ, Tomayko JF. A randomized, double-blind, comparative study to assess the safety and efficacy of topical retapamulin ointment 1% versus oral linezolid in the treatment of secondarily infected traumatic lesions and impetigo due to methicillin-resistant Staphylococcus aureus. Adv Skin Wound Care. 2014 Dec;27(12):548-59. doi: 10.1097/01.ASW.0000456631.20389.ae.