Efficacy and Safety of Garamycin® Sponge in Diabetic Patients With a Moderate or Severe Foot Ulcer Infection

A Randomized, Controlled Study to Investigate the Efficacy and Safety of a Topical Gentamicin-Collagen Sponge in Combination With Systemic Antibiotic Therapy in Diabetic Patients With a Moderate or Severe Foot Ulcer Infection

The purpose of this study is to determine whether Garamycin Sponge (Gentamicin-Collagen sponge) in combination with antibiotics is safe and effective in treating moderate and severe diabetic foot infections.

Study Overview

• Status: Completed
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Drug: Garamycin Sponge (Gentamicin-Collagen sponge); Drug: Systemic Antibiotic

Detailed Description

Infected skin ulcers with diabetes can be very debilitating because they are difficult to heal. Diabetic ulcers are responsible for frequent health care visits, and are a major predictor of amputation. Diabetic ulcers can be caused by a patient's inability to sense pain or warmth as well as peripheral vascular disease, which causes diminished blood flow to the foot. Early aggressive treatment is necessary to treat infection and ultimately prevent the need for amputation.

Gentamicin is an antibiotic that is effective in treating certain kinds of infection. Collagen is a protein that is found in all mammals. The gentamicin sponge being used in this study is commercially available in Switzerland as Garamycin® Sponge. The Garamycin Sponge is a thin flat sponge made out of collagen that comes from bovine tendons and containing gentamicin. When applied to an open ulcer, the collagen breaks down and the gentamicin is released into the ulcer, but very little is absorbed into the blood stream. The high levels of gentamicin in the open infected ulcer may help treat the infection.

All subjects will be given the necessary supplies and taught how to take care their foot ulcer. All subjects will also receive oral an antibiotic. Additionally, subjects who are randomly assigned to receive the gentamicin-collagen sponge will place a gentamicin-collagen sponge on their ulcer during daily wound care.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland
    • Geneva University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Is aged ≥ 18.
• Has diabetes mellitus, according to the American Diabetes Association (ADA) criteria.
• Has an open foot wound with visible inflammation, namely 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 (IDSA).
• Has received appropriate surgical intervention to remove all necrotic and infected bone if diagnosed with osteomyelitis
• Meets certain minimal laboratory criteria.

Exclusion Criteria:

• Has an ulcer infection which, based upon the patient's known history of hypersensitivity cannot be appropriately treated with at least one of the empiric systemic antibiotic regimens per protocol.
• Has received > 48 hours of potentially effective antibiotic therapy and the wounds are clinically improving. If a patient has received an antibiotic within 72 hours, but is not improving or deep-tissue culture results indicate that the infecting pathogen is not susceptible to that antibiotic, the patient may be enrolled.
• Requires or is likely to require treatment with any concomitant topical product or wound therapy during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Garamycin Sponge (Gentamicin-Collagen Sponge); Garamycin Sponge (Gentamicin-Collagen sponge) applied daily plus systemic antibiotic and standard ulcer care	Drug: Garamycin Sponge (Gentamicin-Collagen sponge); Gentamicin Collagen Sponge: 5 × 5 cm in size containing Type I bovine collagen and 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base); Other Names: Sponge arm
Active Comparator: Systemic Antibiotic; Systemic antibiotic therapy and standard ulcer care	Drug: Systemic Antibiotic; Antibiotics options per protocol: Levofloxacin PO 750 mg q.24h or 500 mg q.12h Levofloxacin IV 750 mg q.24h or 500 mg q.12h Amoxicillin/clavulanate PO 500/125 mg q.12h. or q.8h Amoxicillin/clavulanate IV 1000/200 mg q.12h or q.8h Clindamycin PO 300 mg or 450 mg q.6h Clindamycin IV 600 mg q.8h or q.6h Linezolid PO 600 mg q.12h Linezolid IV 600 mg q.12h Metronidazole PO 400 mg or 500 mg q.8h or 500 mg q.6h Metronidazole IV 500 mg q.8h or q.6h Aztreonam IV 1 g or 2 g q.12h or q.8h Piperacillin/tazobactam IV 3000/375 mg q.6h or 4000/500 mg q.8h; Other Names: Control arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cure	Clinical Cure defined as the absence of any clinical, radiological or laboratory evidence of infection	Approximately day 38

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response	Clinical significant improvement is defined as significant improvement of infection but not complete cure (e.g., residual uninfected skin lesions).	up to 38 days
Pathogen Eradication	Microbiological eradication of former infection	up to 38 days

Collaborators and Investigators

• Sponsor: University Hospital, Geneva
• Investigators: Principal Investigator: Ilker Uçkay, University Hospital, Geneva

Publications and helpful links

General Publications

• Uckay I, Kressmann B, Malacarne S, Toumanova A, Jaafar J, Lew D, Lipsky BA. A randomized, controlled study to investigate the efficacy and safety of a topical gentamicin-collagen sponge in combination with systemic antibiotic therapy in diabetic patients with a moderate or severe foot ulcer infection. BMC Infect Dis. 2018 Aug 2;18(1):361. doi: 10.1186/s12879-018-3253-z.
• Uckay I, Kressmann B, Di Tommaso S, Portela M, Alwan H, Vuagnat H, Maitre S, Paoli C, Lipsky BA. A randomized controlled trial of the safety and efficacy of a topical gentamicin-collagen sponge in diabetic patients with a mild foot ulcer infection. SAGE Open Med. 2018 May 13;6:2050312118773950. doi: 10.1177/2050312118773950. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: September 18, 2013
• First Submitted That Met QC Criteria: September 24, 2013
• First Posted (Estimate): September 27, 2013

Study Record Updates

• Last Update Posted (Actual): November 4, 2019
• Last Update Submitted That Met QC Criteria: November 1, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protein Synthesis Inhibitors; Anti-Bacterial Agents; Gentamicins
• Other Study ID Numbers: HUG protocol