Prevention of Infection Using a Topical Gentamicin-Collagen Sponge in Diabetic Patients With An Uninfected Foot Ulcer

A Phase II, Randomized, Parallel, Double-blind, Placebo-controlled Study to Assess Prevention of Infection Using a Topical Gentamicin-Collagen Sponge in Diabetic Patients With Uninfected Lower Extremity Skin Ulcers

The purpose of this study is to determine the safety and efficacy of the topical gentamicin collagen sponge (gentamicin sponge) combined with standard of care (daily wound care, off-loading, diabetic control and debridement by a physician or podiatrist), compared with placebo sponge combined with standard of care, in preventing infection of diabetic lower extremity skin ulcers.

Study Overview

• Status: Terminated
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Drug: gentamicin-collagen sponge; Drug: placebo collagen sponge

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 prevent 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. Subjects will be randomly assigned to receive either the gentamicin-collagen sponge or a plain collagen sponge. The sponge will be applied into the ulcer twice a week during the treatment period.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Pasadena, Maryland, United States, 21122
      • Chesapeake Foot and Ankle Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 skin ulcer below the knee, defined as "uninfected" by the Infectious Disease Society of America Guidelines (Wound lacking purulence or any manifestations of inflammation).
• Has had an x-ray of the affected area within the 2 days immediately preceding or at Visit 1 (Baseline/Randomization) that is negative for osteomyelitis.
• 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.)
• Meets certain minimal laboratory criteria.
• 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 at least 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 study:

Oral, implantable or injectable contraceptives for 3 consecutive months before the Baseline/Randomization Visit.

Total abstinence from sexual intercourse (minimum of 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 Posttreatment Evaluation 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 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 > 5 × 5 cm.
• Has gangrene or infection of the affected limb.
• 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 history of myasthenia gravis or other neurological condition where gentamicin use is contraindicated as determined by the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Daily standard wound care and topical application of the gentamicin-collagen sponge twice weekly	Drug: gentamicin-collagen sponge; 5 × 5 cm sponge; Other Names: Collatamp G
Placebo Comparator: B; Daily standard wound care and topical application of the placebo sponge twice weekly	Drug: placebo collagen sponge; 5 × 5 cm sponge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage of patients who remain free of signs and symptoms of infection until the end of the study	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Time (days) to complete wound closure	Actual time
Time (days) to presence of ≥ 1 of the signs and symptoms of infection	Actual time
Absolute and percent decrease in total wound surface area	End of Study
Pathogen burden in patients who discontinue because of infection	Throughout study period
Treatment emergent Adverse Events	Throughout study period

Collaborators and Investigators

• Sponsor: Innocoll
• Collaborators: Premier Research Group plc

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: April 10, 2008
• First Submitted That Met QC Criteria: April 10, 2008
• First Posted (Estimate): April 16, 2008

Study Record Updates

• Last Update Posted (Estimate): March 23, 2012
• Last Update Submitted That Met QC Criteria: March 22, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Diabetes; Foot Ulcer
• 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; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Gentamicins
• Other Study ID Numbers: INN-TOP-002