The Safety and Efficacy of an Antibiotic Sponge in Diabetic Patients With Moderately Infected Foot Ulcers

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 daily wound care and an oral antibiotic (levofloxacin) is safe and effective in treating moderately infected skin ulcers compared to treatment only with standard daily wound care and an oral antibiotic (levofloxacin).

Detailed Description
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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-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 their foot ulcer. All subjects will also receive oral an antibiotic (levofloxacin). 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.

Official Title
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A Randomized, Controlled, Open Label Study of the Safety and Efficacy of a Topical Gentamicin Collagen Sponge Combined With An Antibiotic Compared to Antibiotic Therapy Alone in Diabetic Patients With Moderately Infected Foot Ulcers

Conditions
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Diabetic Foot Ulcer

Intervention / Treatment
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* Drug: gentamicin-collagen sponge and levofloxacin
* Drug: Levofloxacin only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is a man or woman aged ≥ 18 and ≤ 80 years. Has diabetes mellitus, according to the American Diabetes Association criteria. Has a single infected skin ulcer below the knee, defined as moderate by the Infectious Disease Society of America (IDSA) Guidelines for whom, in the Investigator's opinion, intravenous (IV) or oral antimicrobial therapy is appropriate Has had an x ray of the infected area within the 2 days immediately preceding or at Visit 1 (Baseline/Randomization) to document the presence or absence of osteomyelitis. Patients with osteomyelitis must receive appropriate surgical intervention to remove all necrotic and infected bone and otherwise meet enrollment criteria before being enrolled in the study. Meets certain minimal laboratory criteria Has an ankle brachial index (ABI) > or = 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 > or = 40 mm Hg on limb with ulcer.) If female, is nonpregnant (negative pregnancy test results 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 a medically acceptable methods of birth control and agrees to continue with the regimen throughout the study 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 a target ulcer with a wound size > 10 × 10 cm. Has gangrenous tissue of the affected limb that cannot be removed with a single debridement. Has wound known to contain isolates resistant to levofloxacin. 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]). 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. Has serum creatinine > 3 mg/dL, is undergoing dialysis (renal or peritoneal) or has a 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>Gentamicin sponge applied into wound plus levofloxacin, 750 mg by mouth (po) or intravenous (IV) every 24 hours or, if ulcer culture results show resistance to levofloxacin, alternative antimicrobial therapy as determined by susceptibility testing | Drug: gentamicin-collagen sponge and levofloxacin<br>* Topical Gentamicin Collagen Sponge: 10 × 10 cm in size And 750 mg tablet po every 24 hours or 750 mg IV administered by slow infusion over 90 minutes every 24 hours.<br>* Other names: Collatamp G;|
| Active Comparator: B<br>Levofloxacin, 750 mg po or IV every 24 hours or, if ulcer culture results show resistance to levofloxacin, alternative antimicrobial therapy as determined by susceptibility testing | Drug: Levofloxacin only<br>* levofloxacin, 750 mg tablet po every 24 hours or 750 mg IV administered by slow infusion over 90 minutes every 24 hours<br>* Other names: Tavanic, Levaquin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Clinical Cure at Visit 3 (Day 7) | Number of participants with a clinical cure in each treatment group at Visit 3 (Day 7). Clinical Cure is defined as positive clinical response and with pathogen eradication. | Day 7 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Positive Clinical Response at Each Time Point | Number of patients with positive clinical response, defined as those with a clinical outcome of clinical cure or clinical improvement in each treatment group at/by each time point | Day 3, 7, 10,14, 21, 28 and 42 | 
| Number of Participants With a Clinical Cure at Each Visit Except Visit 3 (Day 7) | clinical cure is defined as having a positive clinical response and with pathogen eradication | Day 3, 10, 14, 21, 28 & 42 | 
| Number of Participants With Pathogen Eradication by Visit |  | Day 3, 7, 10, 14, 21 & 28 | 
| Change From Baseline in Total Wound Surface Area Measured in cm^2 | Wound Surface Area was measured in cm² Actual Values Total wound surface area was compared across treatments using 2-sample t-tests. Wound tracings were obtained at study visits by trained study personnel who were blinded to the patient data and regimen. A centralized imaging facility provided both wound perimeter and area measurements. | Day 3, 7, 10, 14, 21, 28 & 42 | 
| Time to Clinical Cure | clinical cure is defined as having a positive clinical response and with pathogen eradication | Days 1 through 49 | 
| Visual Analog Scale (VAS) for Pain Assessment | Measured on a Visual Analog Pain Scale (VAS) with the lowest possible value of 0 and highest 100 (0 - 100) at each time point. A lower score is better which means the patient experience lower pain. The score is calculated using the number of hours * the VAS score. This represents the AUC (Area Under the Curve) of the pain intensities when calculated with the trapezoidal rule. For each measure outcome - the minimum score is 0 and the maximum score is 100* the number of hours in that period. | Day 3, 7, 10, 14, 21, 28 & 42 | 
| Lipsky Wound Score | The Lipsky wound scoring scale consists of scoring categories for purulent drainage, non-purulent drainage, erythema, induration, tenderness, pain, local warmth and wound measurements. This wound scoring system allows us to take the size and depth of the wound into consideration as well as all signs and symptoms of inflammation and infection. A quantitative score that assess wounds both at baseline and during therapy to compare wound scores over time. The higher the score the worse the inflammation and/or infection is. The Lowest score possible is 3 and the highest score possible is 64. | Days 3, 7, 10, 14, 21, 28, 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, ulcers, ulcerations, infection