Study of a Topical Gentamicin-Collagen Sponge Along With Systemic Antibiotic in Infected Diabetic Foot Ulcers
Condition: Foot Ulcer, Diabetic; Infection
MeSH terms: Diabetic Foot; Foot Ulcer; Ulcer
Intervention: Gentamicin collagen sponge; Placebo
Intervention description: Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base); Matching collagen sponge
Intervention MeSH terms: Gentamicins
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 612.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

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.
    

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