Safety and Efficacy of an Antibiotic Sponge in Diabetic Patients With a Mild Infection of a Foot Ulcer

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the gentamicin-collagen sponge when combined with standard of daily wound care is safe and effective in treating mildly infected skin ulcers compared to treatment with an oral antibiotic (levofloxacin) and standard daily wound care.

Detailed Description
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Infected skin ulcers in patients 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 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-collagen sponge is a thin flat sponge made out of collagen that comes from cow 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. In this study, all subjects will be given the necessary supplies and taught how to take care of their foot ulcer. Subjects who are randomly assigned to the gentamicin-collagen sponge treatment group will place a gentamicin-collagen sponge on their ulcer during daily wound care. Subjects who are randomly assigned to the oral levofloxacin treatment group will also perform daily wound care, but they will not be given the gentamicin-collagen sponge. Instead they will be given the antibiotic, levofloxacin to take by mouth during the treatment period.

Official Title
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A Study to Investigate the Safety and Efficacy of a Topical Gentamicin-Collagen Sponge Compared to Levofloxacin in Diabetic Patients With a Mild Infection of a Lower Extremity Skin Ulcer

Conditions
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Diabetic Foot Ulcer

Intervention / Treatment
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* Drug: gentamicin-collagen sponge
* Drug: Levofloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is a man or woman aged 18 to 80 years. Has diabetes mellitus, according to the American Diabetes Association criteria. Has a single infected skin ulcer below the knee, defined as mild by the Infectious Disease Society of America (IDSA) Guidelines, for whom, in the Investigator's judgment, topical or oral antimicrobial therapy is appropriate (Mild infection severity: The presence of ≥ 2 manifestations of inflammation (purulence or erythema, pain, tenderness, warmth or induration) but any cellulitis/erythema extends ≤ 2 cm around the ulcer, and the infection is limited to the skin or superficial subcutaneous tissue, with no other local complications or acute, systemic illness). Has had an x-ray of the infected area within the 2 days immediately preceding or at Visit 1 (Baseline/Randomization) that is negative for osteomyelitis. Meets the certain minimal laboratory criteria Has an ankle-brachial index (ABI) ≥ 0.7 and ≤ 1.3. (Note: Patients with ABI < 0.7 or > 1.3 may be included if they have either a transcutaneous oxygen pressure or a toe pressure ≥ 40 mm Hg on the limb with the target ulcer.) If female, is nonpregnant (negative pregnancy tests at the Baseline/Randomization Visit) and nonlactating. If female, is either not of childbearing potential (defined as postmenopausal for ≥ 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy or hysterectomy]) or practicing 1 of the following medically-acceptable methods of birth control and agrees to continue with the regimen throughout the duration of the study: Oral, implantable or injectable contraceptives for 3 consecutive months before the Baseline/Randomization Visit Total abstinence from sexual intercourse (≥ 1 complete menstrual cycle before the Baseline/Randomization Visit) Intrauterine device (IUD) Double barrier method (condoms, sponge, diaphragm or vaginal ring with spermicidal jellies or cream) Willing to return to the study facility for the Final Study Visit. Must be able to fluently speak and understand English and be able to provide meaningful written informed consent for the study Exclusion Criteria: Has a known history of hypersensitivity to gentamicin (or other systemic aminoglycosides) or levofloxacin or drugs in the same class, or any of the test article or reference product components. Has a known hypersensitivity to bovine collagen. Has any uncontrolled illnesses that, in the opinion of the Investigator, would interfere with interpreting the results of the study. Has an infecting pathogen known to be intermediate or resistant in vitro to levofloxacin. Patients enrolled into the study presumptively will be discontinued if their cultured organism is intermediate or resistant to levofloxacin. Has a target ulcer with a wound size > 5 × 5 cm. Has gangrenous tissue of the affected limb that cannot be removed with a single debridement. Has a wound associated with prosthetic material or device. Received any topical or systemic antimicrobial therapy within the 2 weeks prior to study entry (Visit 1 [Day 1]). Has documented osteomyelitis. If severely immunocompromised, may be excluded at the discretion of the Investigator. Has a history of alcohol or substance abuse in the past 12 months. Is undergoing dialysis (renal or peritoneal) or has history of kidney transplant. 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 tendon disorders related to fluoroquinolone administration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Daily topical gentamicin sponge and standard daily wound care | Drug: gentamicin-collagen sponge<br>* Inserted daily into open ulcer<br>|
| Active Comparator: B<br>Daily oral levofloxacin 750 mg and standard daily wound care | Drug: Levofloxacin<br>* 750mg oral levofloxacin daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Clinical Outcome of Clinical Cure | Number of Participants with a clinical outcome of clinical cure at final visit. Clinical Cure is defined as positive clinical response and with pathogen eradication. | Final Study Visit (Day 21 [or 28 or 35]) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Clinical Outcome of Clinical Cure in Each Treatment Group | Number of participants with a clinical outcome of clinical cure in each treatment group at/by each time point (except the Final Study Visit). Clinical Cure is defined as positive clinical response and with pathogen eradication. | Each time point (Day 3, 7 [14 and 21 if necessary]) | 
| Time to Baseline Pathogen Eradication |  | assessed at each time point on days 7, 14, 21, time to pathogen eradication from baseline up to day 21 reported | 
| Number of Participants With Complete Wound Closure by Each Visit |  | At each timepoint Day 3, 7, 14 & 21 | 
| Time to Clinical Cure | Time to Clinical Cure is measured by days to the first observed cure. Clinical Cure is defined as positive clinical response and with pathogen eradication. | Actual time assessed (Day 1, 3, 7 [14 and 21 if necessary] and Day 21 [or 28 or 35]) | 
| Time to Pathogen Eradication | Time to Baseline Pathogen Eradication summed | Actual time assessed (Day 1-21 | 
| Time to Positive Clinical Response |  | (Day 1, 3, 7 [14 and 21 if necessary] and Day 21 [or 28 or 35]) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Foot Ulcer