A Phase 3 Randomized, Placebo-Controlled, Blinded Study to Investigate the Safety and Efficacy of a Topical Gentamicin-Collagen Sponge in Combination With Systemic Antibiotic Therapy in Diabetic Patients With an Infected Foot Ulcer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 612
- 主要终点
- Clinical Cure (Resolution of All Clinical Signs and Symptoms of Infection)
研究概览
简要总结
This is a phase 3, randomized, controlled, blinded, multicenter study conducted in 3 parallel cohorts of diabetic patients with at least 1 infected foot ulcer. Patients will be randomized to receive 1 of 3 study treatments; systemic antibiotic therapy and standard ulcer care with either (A) daily application of a gentamicin-sponge, (B) daily application of a placebo-sponge or (C) no-sponge, in the ratio 2:1:1.
Patients will be treated for approximately 28 days and return to the clinic weekly for safety and efficacy assessments. After completing treatment, patients will return to the clinic for scheduled follow-up visits approximately 10, 30, 60 and 90 days after treatment is stopped.
详细描述
This is a phase 3, randomized, controlled, blinded, multicenter study conducted in 3 parallel cohorts of diabetic patients with at least 1 infected foot ulcer. Patients will be randomized using an electronic randomization system to receive 1 of 3 study treatments; systemic antibiotic therapy and standard ulcer care with either (A) daily application of a gentamicin-sponge, (B) daily application of a placebo-sponge or (C) no-sponge, in the ratio 2:1:1. The investigator will be blinded to the patient's treatment group assignment and patients randomized to one of the 2 sponge groups will be blinded as to whether the sponge is active or placebo.
If a patient has multiple infected ulcers, the assigned treatment will be administered to all infected ulcers. The investigator will determine the highest severity ulcer to be used for all efficacy evaluations and will also determine the size and number of sponges (up to 4) that a patient will use in order to completely cover all infected ulcers. The investigator will prescribe an empiric systemic antibiotic therapy based on protocol instructions.
Patients will be treated for approximately 28 days and return to the clinic weekly for safety and efficacy assessments. The investigator will stop study treatment if a patient achieves clinical cure by or after the 3rd treatment visit (approximately study day 15). After completing treatment, patients will return to the clinic for scheduled follow-up visits or until ulcer closure. The final efficacy assessments used in the primary efficacy analyses will be obtained at the first follow-up visit approximately 10 days after treatment is stopped. The remaining follow-up visits will occur at approximately 30, 60 and 90 days after treatment is stopped when patients will be assessed for ulcer closure and any re-infection.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has diabetes mellitus, according to the American Diabetes Association (ADA) criteria.
- •Has at least 1 skin ulcer located on or below the malleolus that presents with the following clinical manifestations of a moderate or severe infection based on the Infectious Disease Society of America guidelines for the "Diagnosis and Treatment of Diabetic Foot Infections" (CID 2012; 54:132-173) (IDSA guidelines):
- •has ≥ 2 manifestations of inflammation (local swelling or induration, erythema, local tenderness or pain, local warmth, purulent discharge (thick, opaque to white or sanguineous secretion)
- •has ≥ 1 of the following characteristics: erythema > 2cm, or involving structures deeper than skin and subcutaneous tissues (e.g. abscess, osteomyelitis, septic arthritis, fasciitis) For patients with multiple infected ulcers, the ulcer with the highest Diabetic Foot Infection Wound score (DFI score) must be on or below the malleolus and all infected ulcers must be completely coverable using no more than 4 sponges (sponges cannot be cut).
- •Has documented adequate arterial perfusion in the affected limb(s) (either palpable dorsalis pedis and posterior tibial pulses, or normal Doppler wave forms, a toe blood pressure ≥ 45 mm Hg or participation is approved by a vascular surgeon)
- •Has received appropriate surgical intervention to remove all necrotic and infected bone if diagnosed with osteomyelitis.
- •Has received appropriate surgical debridement to remove all gangrenous tissue.
排除标准
- •Has a known history of hypersensitivity to gentamicin (or other aminoglycosides).
- •Has a known or suspected hypersensitivity to bovine collagen.
- •Has an ulcer infection which, based upon the patient's known history of hypersensitivity and/or as otherwise in the opinion of the investigator, cannot be adequately treated with at least one of the empiric systemic antibiotic regimens allowed by this protocol.
- •Has an ulcer associated with prosthetic material or an implanted device.
- •Has received any systemic or topical antibiotic therapy for any reason within 7 days of randomization unless it was administered to specifically treat the infected ulcer(s) and only within 36 hours of randomization.
- •Requires or is likely to require treatment with any concomitant topical product or wound therapy before the first follow-up study visit.
- •Is severely immunocompromised, or likely to become severely immunocompromised during the study, in the opinion of the investigator.
- •Has a history of myasthenia gravis or other neurological condition where gentamicin use is contraindicated as determined by the investigator.
- •Has a history of epilepsy.
- •Has a history of alcohol or substance abuse in the past 12 months.
- •Has an uncontrolled illness that, in the opinion of the investigator, is likely to cause the patient to be withdrawn from the trial or would otherwise interfere with interpreting the results of the study
研究组 & 干预措施
Gentamicin sponge group
Topical Gentamicin Collagen Sponge: Up to four collagen sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.
干预措施: Gentamicin collagen sponge (Drug)
Placebo sponge group
Matching placebo collagen sponge administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.
干预措施: Placebo (Other)
结局指标
主要结局
Clinical Cure (Resolution of All Clinical Signs and Symptoms of Infection)
时间窗: approximately 10 days after end of treatment
The primary efficacy variable is the percent of patients with a clinical outcome of clinical cure (Resolution of all clinical signs and symptoms of infection) at F/U visit 1
次要结局
- Time to Clinical Cure(Approximately 10 days after end of treatment)
- Reinfection (Percent of Patients With Re-infection)(Approximately 90 days after end of treatment)
- Amputation (Percent of Patients That Have an Amputation Associated With the Target Ulcer)(Within approximately 90 days of end of treatment)
- Clinical Cure and Baseline Pathogen Eradication (Resolution of All Clinical Signs and Symptoms of Infection) and Baseline Pathogen Eradication)(Approximately 10 days after end of treatment)
- Ulcer Closure (Percent of Patients With Target Ulcer Closure)(within approximately 30 days of end of treatment)