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

Phase 3

Completed

Conditions: Infection
Foot Ulcer, Diabetic

Interventions: Drug: Gentamicin Collagen sponge
Other: Placebo

Registration Number: NCT02447172

Lead Sponsor: Innocoll

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 524

Inclusion Criteria

Not provided

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Gentamicin sponge group	Gentamicin Collagen sponge	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.
Placebo sponge group	Placebo	Matching placebo collagen sponge administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.

Primary Outcome Measures

Name	Time	Method
Percent of Patients With a Clinical Outcome of Clinical Cure (Resolution of All Clinical Signs and Symptoms of Infection)	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

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Re-infections	up to 90 days after treatment stopped
Time to Clinical Response	up to 90 days after treatment stopped	Time in Days to Clinical Cure
Percent of Subjects That Had an Amputation Associated With the Target Ulcer	up to 90 days after treatment stopped	Modified Intent-to-Treat Population - Percent of subjects that had an amputation associated with the target ulcer