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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 410
- 试验地点
- 1
- 主要终点
- Number of Participants Achieving Clinical Response at Follow-up Who Had Methicillin-resistant Staphlococcus Aureus (MRSA) as a Baseline Pathogen
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 2 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •previous hypersensitivity to pleuromutilins or oxazolidinones
- •phenylketonuria or known hypersensitivity to aspartame
- •secondarily-infected animal/human bite, or puncture wound
- •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)
研究组 & 干预措施
Retapamulin
干预措施: Retpamulin Ointment, 1% (Drug)
Linezolid
干预措施: Linezolid (Drug)
结局指标
主要结局
Number of Participants Achieving Clinical Response at Follow-up Who Had Methicillin-resistant Staphlococcus Aureus (MRSA) as a Baseline Pathogen
时间窗: 7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid
Follow-up is defined as 7-9 days post-therapy: Day 12-14 for retapamulin; Day 17-19 for linezolid. Clinical success at follow-up was defined as the resolution of clinically meaningful signs and symptoms of infection recorded at baseline, including a pus/exudate skin infection rating scale (SIRS) score of "0." The SIRS is used by the investigator to evaluate infected lesions. Scores on the SIRS range from 0 (absent) to 6 (severe).
次要结局
- Number of Participants With Clinical Response at Follow-up(7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid)
- Number of Participants With the Indicated Clinical Outcome at the End of Therapy(2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid)
- Number of Baseline Pathogens With the Indicated Microbiological Outcome at the End of Therapy(2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid)
- Number of Participants Who Achieved Microbiological Response (MR) at Follow-up (FU) Who Had a Baseline Pathogen (BP)(7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid)
- Number of Participants Achieving Microbiological Response (MR) at Follow-up (FU) Who Had MRSA as a Baseline Pathogen (BP)(7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid)
- Number of Participants With the Indicated Clinical Outcome at the End of Therapy Who Had MRSA as a Baseline Pathogen(2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid)
- Number of Participants With the Indicated Microbiological Outcome at the End of Therapy Who Had MRSA as a Baseline (BL) Pathogen(2-4 days post-therapy; Day 7-9 for retapamulin and Day 12-14 for linezolid)
- Mean Scores on the Skin Infection Rating Scale at Visits 1, 2, 3, 4, and 5(Visits 1 (Day 1), 2 (Day 3-4), 3 (Day 7-9), 4 (Day 12-14), and 5 (Day 17-19))
- Mean Wound Size at Visits 1, 2, 3, 4, and 5(Visits 1 (Day 1), 2 (Day 3-4), 3 (Day 7-9), 4 (Day 12-14), and 5 (Day 17-19))
- Number of Participants With Therapeutic Response at Follow-up(7-9 days post-therapy; Day 12-14 for retapamulin and Day 17-19 for linezolid)