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

Sponsor:	Innocoll Technologies
Collaborator:	Premier Research Group plc
Information provided by:	Innocoll Technologies
ClinicalTrials.gov Identifier:	NCT00659646

Purpose

The purpose of this study is to determine whether the gentamicin-collagen sponge (Collatamp G topical) 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).

Condition	Intervention	Phase
Diabetic Foot Ulcer	Drug: gentamicin-collagen sponge and levofloxacin Drug: Levofloxacin only	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics Diabetic Foot Foot Health

Drug Information available for: Ofloxacin Levofloxacin Ofloxacin hydrochloride Gentamicins

U.S. FDA Resources

Further study details as provided by Innocoll Technologies:

Primary Outcome Measures:

The percent of patients with a clinical outcome of "clinical cure" in each treatment group at Visit 3 [ Time Frame: Day 7 of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The percent of patients with a positive clinical response at each time point [ Time Frame: Every time point ] [ Designated as safety issue: No ]
The percent of patients with a "clinical cure" [ Time Frame: Every time point ] [ Designated as safety issue: No ]
The percent of patients with pathogen eradication [ Time Frame: Every timepoint ] [ Designated as safety issue: No ]
Absolute change in total wound surface area in each treatment group [ Time Frame: Every time point ] [ Designated as safety issue: No ]
Time to clinical cure [ Time Frame: Actual time assessed ] [ Designated as safety issue: No ]
Time to positive clinical response [ Time Frame: Actual time assessed ] [ Designated as safety issue: No ]
Time on parenteral antimicrobial therapy [ Time Frame: Actual time assessed ] [ Designated as safety issue: No ]
Visual Analog Scale (VAS) for pain assessment [ Time Frame: Every timepoint ] [ Designated as safety issue: No ]
Lipsky wound score [ Time Frame: Every timepoint ] [ Designated as safety issue: No ]
Treatment emergent adverse events [ Time Frame: Throughout study period ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	75
Study Start Date:	April 2008
Estimated Study Completion Date:	April 2009
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental 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 Collatamp G Topical Gentamicin Collagen Sponge: 10 × 10 cm in size containing 280 mg of Type I bovine collagen and 200 mg of gentamicin sulfate (equivalent to 130 mg gentamicin base) OR 5 × 5 cm in size containing 70 mg of Type I bovine collagen and 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) (gentamicin sulfate 2 mg/cm2 [equivalent to 1.3 mg/cm2 of gentamicin base]), depending on the size of the wound. The patient will continue using the same size sponge for the duration of the study. And 750 mg tablet po every 24 hours or 750 mg IV administered by slow infusion over 90 minutes every 24 hours.
B: Active Comparator 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 levofloxacin, 750 mg tablet po every 24 hours or 750 mg IV administered by slow infusion over 90 minutes every 24 hours

Arms

Assigned Interventions

A: Experimental

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

Collatamp G Topical Gentamicin Collagen Sponge: 10 × 10 cm in size containing 280 mg of Type I bovine collagen and 200 mg of gentamicin sulfate (equivalent to 130 mg gentamicin base) OR 5 × 5 cm in size containing 70 mg of Type I bovine collagen and 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) (gentamicin sulfate 2 mg/cm2 [equivalent to 1.3 mg/cm2 of gentamicin base]), depending on the size of the wound. The patient will continue using the same size sponge for the duration of the study.

And 750 mg tablet po every 24 hours or 750 mg IV administered by slow infusion over 90 minutes every 24 hours.

B: Active Comparator

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

levofloxacin, 750 mg tablet po every 24 hours or 750 mg IV administered by slow infusion over 90 minutes every 24 hours

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-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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00659646

Contacts

Contact: Lisa Hemsen

860-610-5530 ext 5530

skinulcers@premier-research.com

Locations

United States, Florida
Karr Foot Kare PA	Recruiting
Lakeland, Florida, United States, 33813
Principal Investigator: Jeffrey C. Karr, DPM

Sponsors and Collaborators

Innocoll Technologies

Premier Research Group plc

Investigators

Study Director:

David Prior

Innocoll Technologies

More Information

No publications provided

Responsible Party:	Innocoll Holdings Inc. ( David Prior, Executive Vice President, Scientific Affairs )
Study ID Numbers:	INN-TOP-003
Study First Received:	April 11, 2008
Last Updated:	January 8, 2009
ClinicalTrials.gov Identifier:	NCT00659646 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Innocoll Technologies:

Diabetes
ulcers
ulcerations
infection

Additional relevant MeSH terms:

Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Ofloxacin
Renal Agents
Foot Diseases
Diabetic Angiopathies
Anti-Bacterial Agents
Pathologic Processes
Therapeutic Uses
Cardiovascular Diseases
Diabetes Complications
Nucleic Acid Synthesis Inhibitors
Foot Ulcer
Skin Diseases

Diabetic Neuropathies
Ulcer
Diabetes Mellitus
Vascular Diseases
Endocrine System Diseases
Anti-Infective Agents, Urinary
Enzyme Inhibitors
Pharmacologic Actions
Protein Synthesis Inhibitors
Gentamicins
Skin Ulcer
Leg Ulcer
Diabetic Foot

ClinicalTrials.gov processed this record on February 08, 2010