Study of a Topical Gentamicin-Collagen Sponge Along With Systemic Antibiotic in Infected Diabetic Foot Ulcers

NCT ID: NCT02427802

Last Updated: 2021-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 612 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2016-10-31

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.

Conditions

Foot Ulcer, Diabetic; Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Gentamicin collagen sponge

Intervention Type: DRUG

Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base)

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Matching collagen sponge

No sponge group

Systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Gentamicin collagen sponge

Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base)

Intervention Type: DRUG

Placebo

Matching collagen sponge

Intervention Type: OTHER

Other Intervention Names

Cogenzia

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Innocoll

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nigel Jones

Role: STUDY_DIRECTOR

Vice President, Global Clinical Operations, Innocoll Pharmaceutical

Locations

Anniston, Alabama, United States

Mobile, Alabama, United States

Mesa, Arizona, United States

Phoenix, Arizona, United States

Fayetteville, Arkansas, United States

Jonesboro, Arkansas, United States

Little Rock, Arkansas, United States

Little Rock, Arkansas, United States

Bakersfield, California, United States

Chino, California, United States

Corona, California, United States

Fountain Valley, California, United States

Fresno, California, United States

Fresno, California, United States

Fresno, California, United States

Long Beach, California, United States

Los Angeles, California, United States

Oakland, California, United States

San Francisco, California, United States

Sylmar, California, United States

Norwalk, Connecticut, United States

Washington D.C., District of Columbia, United States

Clermont, Florida, United States

Cooper City, Florida, United States

Coral Gables, Florida, United States

Coral Gables, Florida, United States

DeLand, Florida, United States

Fleming Island, Florida, United States

Hialeah, Florida, United States

Hialeah, Florida, United States

Hollywood, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami Lakes, Florida, United States

Miami Springs, Florida, United States

New Port Richey, Florida, United States

St. Petersburg, Florida, United States

West Palm Beach, Florida, United States

Weston, Florida, United States

Augusta, Georgia, United States

Columbus, Georgia, United States

Marietta, Georgia, United States

Idaho Falls, Idaho, United States

Avon, Indiana, United States

Mooresville, Indiana, United States

Muncie, Indiana, United States

Baltimore, Maryland, United States

Phoenix, Maryland, United States

Boston, Massachusetts, United States

Flint, Michigan, United States

Butte, Montana, United States

Great Falls, Montana, United States

Las Vegas, Nevada, United States

North Brunswick, New Jersey, United States

Somerset, New Jersey, United States

Hopewell Junction, New York, United States

New Windsor, New York, United States

Durham, North Carolina, United States

Lima, Ohio, United States

Oklahoma City, Oklahoma, United States

Oklahoma City, Oklahoma, United States

Philadelphia, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Greenville, South Carolina, United States

Myrtle Beach, South Carolina, United States

West Columbia, South Carolina, United States

Dallas, Texas, United States

Houston, Texas, United States

Lampasas, Texas, United States

Lubbock, Texas, United States

McAllen, Texas, United States

North Richland Hills, Texas, United States

San Antonio, Texas, United States

San Antonio, Texas, United States

San Antonio, Texas, United States

Sugar Land, Texas, United States

Webster, Texas, United States

Norfolk, Virginia, United States

Virginia Beach, Virginia, United States

Wenatchee, Washington, United States

Countries

United States

Other Identifiers

INN-TOP-004

Identifier Type: -

Identifier Source: org_study_id