Clinical trial NCT02427802: Study of a Topical Gentamicin-Collagen Sponge Along With Systemic Antibiotic in Infected Diabetic Foot Ulcers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Foot Ulcer, Diabetic
Infection
Lead sponsor: Innocoll
Sponsor class: INDUSTRY
First posted: 2015-04-28
Enrollment: 612
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Clinical Cure (Resolution of All Clinical Signs and Symptoms of Infection)
timeFrame: approximately 10 days after end of treatment
Secondary outcomes:
measure: Clinical Cure and Baseline Pathogen Eradication (Resolution of All Clinical Signs and Symptoms of Infection) and Baseline Pathogen Eradication)
timeFrame: Approximately 10 days after end of treatment
measure: Reinfection (Percent of Patients With Re-infection)
timeFrame: Approximately 90 days after end of treatment
measure: Time to Clinical Cure
timeFrame: Approximately 10 days after end of treatment
measure: Amputation (Percent of Patients That Have an Amputation Associated With the Target Ulcer)
timeFrame: Within approximately 90 days of end of treatment
measure: Ulcer Closure (Percent of Patients With Target Ulcer Closure)
timeFrame: within approximately 30 days of end of treatment
Other outcomes:
Locations:
city: Anniston
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Mesa
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Fayetteville
country: United States
state: Arkansas
city: Jonesboro
country: United States
state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: Bakersfield
country: United States
state: California
city: Chino
country: United States
state: California
city: Corona
country: United States
state: California
city: Fountain Valley
country: United States
state: California
city: Fresno
country: United States
state: California
city: Fresno
country: United States
state: California
city: Fresno
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Oakland
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Sylmar
country: United States
state: California
city: Norwalk
country: United States
state: Connecticut
city: Washington
country: United States
state: District of Columbia
city: Clermont
country: United States
state: Florida
city: Cooper City
country: United States
state: Florida
city: Coral Gables
country: United States
state: Florida
city: Coral Gables
country: United States
state: Florida
city: DeLand
country: United States
state: Florida
city: Fleming Island
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Miami Lakes
country: United States
state: Florida
city: Miami Springs
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Weston
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Columbus
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Idaho Falls
country: United States
state: Idaho
city: Avon
country: United States
state: Indiana
city: Mooresville
country: United States
state: Indiana
city: Muncie
country: United States
state: Indiana
city: Baltimore
country: United States
state: Maryland
city: Phoenix
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Flint
country: United States
state: Michigan
city: Butte
country: United States
state: Montana
city: Great Falls
country: United States
state: Montana
city: Las Vegas
country: United States
state: Nevada
city: North Brunswick
country: United States
state: New Jersey
city: Somerset
country: United States
state: New Jersey
city: Hopewell Junction
country: United States
state: New York
city: New Windsor
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Lima
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Greenville
country: United States
state: South Carolina
city: Myrtle Beach
country: United States
state: South Carolina
city: West Columbia
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Lampasas
country: United States
state: Texas
city: Lubbock
country: United States
state: Texas
city: McAllen
country: United States
state: Texas
city: North Richland Hills
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Sugar Land
country: United States
state: Texas
city: Webster
country: United States
state: Texas
city: Norfolk
country: United States
state: Virginia
city: Virginia Beach
country: United States
state: Virginia
city: Wenatchee
country: United States
state: Washington
Study officials:
affiliation: Vice President, Global Clinical Operations, Innocoll Pharmaceutical
name: Nigel Jones
role: STUDY_DIRECTOR
References: