Diabetic Foot Ulcer
Conditions
Keywords
Diabetic Foot Ulcer
Brief summary
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
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.
Interventions
Inserted daily into open ulcer
DRUGLevofloxacin
750mg oral levofloxacin daily
Sponsors
Premier Research
Innocoll
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Clinical Outcome of Clinical Cure | Final Study Visit (Day 21 [or 28 or 35]) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Number of Participants With a Clinical Outcome of Clinical Cure in Each Treatment Group | Each time point (Day 3, 7 [14 and 21 if necessary]) | 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. |
| Time to Pathogen Eradication | Actual time assessed (Day 1-21 | Time to Baseline Pathogen Eradication summed |
| Time to Positive Clinical Response | (Day 1, 3, 7 [14 and 21 if necessary] and Day 21 [or 28 or 35]) | — |
| Time to Clinical Cure | Actual time assessed (Day 1, 3, 7 [14 and 21 if necessary] and Day 21 [or 28 or 35]) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gentamicin Sponge Daily topical gentamicin sponge and standard daily wound care
gentamicin-collagen sponge: Inserted daily into open ulcer | 47 |
| Levofloxacin Daily oral levofloxacin 750 mg and standard daily wound care
Levofloxacin: 750mg oral levofloxacin daily | 22 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lack of Efficacy | 2 | 1 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Protocol Violation | 13 | 7 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Levofloxacin | Total | Gentamicin Sponge |
|---|---|---|---|
| Age, Continuous | 58.9 Years STANDARD_DEVIATION 14.04 | 59.4 Years STANDARD_DEVIATION 11.57 | 59.6 Years STANDARD_DEVIATION 10.54 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 10 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 57 Participants | 40 Participants |
| Sex: Female, Male Female | 12 Participants | 41 Participants | 29 Participants |
| Sex: Female, Male Male | 10 Participants | 28 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 22 |
| other Total, other adverse events | 15 / 47 | 5 / 22 |
| serious Total, serious adverse events | 0 / 47 | 0 / 22 |
Outcome results
Primary
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.
Time frame: Final Study Visit (Day 21 [or 28 or 35])
Population: Modified Intent-to-Treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gentamicin Sponge | Number of Participants With a Clinical Outcome of Clinical Cure | 14 Participants |
| Levofloxacin | Number of Participants With a Clinical Outcome of Clinical Cure | 7 Participants |
Secondary
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.
Time frame: Each time point (Day 3, 7 [14 and 21 if necessary])
Population: Modified intent to treat population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gentamicin Sponge | Number of Participants With a Clinical Outcome of Clinical Cure in Each Treatment Group | Visit 3 Day 7 | 4 Participants |
| Gentamicin Sponge | Number of Participants With a Clinical Outcome of Clinical Cure in Each Treatment Group | Visit 5 Day 21 | 8 Participants |
| Gentamicin Sponge | Number of Participants With a Clinical Outcome of Clinical Cure in Each Treatment Group | Visit 4 Day 14 | 4 Participants |
| Gentamicin Sponge | Number of Participants With a Clinical Outcome of Clinical Cure in Each Treatment Group | Final Study Visit | 14 Participants |
| Gentamicin Sponge | Number of Participants With a Clinical Outcome of Clinical Cure in Each Treatment Group | Visit 2 Day 3 | 0 Participants |
| Levofloxacin | Number of Participants With a Clinical Outcome of Clinical Cure in Each Treatment Group | Final Study Visit | 7 Participants |
| Levofloxacin | Number of Participants With a Clinical Outcome of Clinical Cure in Each Treatment Group | Visit 2 Day 3 | 0 Participants |
| Levofloxacin | Number of Participants With a Clinical Outcome of Clinical Cure in Each Treatment Group | Visit 3 Day 7 | 0 Participants |
| Levofloxacin | Number of Participants With a Clinical Outcome of Clinical Cure in Each Treatment Group | Visit 4 Day 14 | 6 Participants |
| Levofloxacin | Number of Participants With a Clinical Outcome of Clinical Cure in Each Treatment Group | Visit 5 Day 21 | 0 Participants |
Secondary
Number of Participants With Complete Wound Closure by Each Visit
Time frame: At each timepoint Day 3, 7, 14 & 21
Population: mITT
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gentamicin Sponge | Number of Participants With Complete Wound Closure by Each Visit | Visit 2 Day 3 | 0 Participants |
| Gentamicin Sponge | Number of Participants With Complete Wound Closure by Each Visit | Visit 3 Day 7 | 2 Participants |
| Gentamicin Sponge | Number of Participants With Complete Wound Closure by Each Visit | Visit 4 Day 14 | 3 Participants |
| Gentamicin Sponge | Number of Participants With Complete Wound Closure by Each Visit | Visit 5 Day 21 | 4 Participants |
| Levofloxacin | Number of Participants With Complete Wound Closure by Each Visit | Visit 5 Day 21 | 2 Participants |
| Levofloxacin | Number of Participants With Complete Wound Closure by Each Visit | Visit 2 Day 3 | 0 Participants |
| Levofloxacin | Number of Participants With Complete Wound Closure by Each Visit | Visit 4 Day 14 | 2 Participants |
| Levofloxacin | Number of Participants With Complete Wound Closure by Each Visit | Visit 3 Day 7 | 0 Participants |
Secondary
Time to Baseline Pathogen Eradication
Time frame: assessed at each time point on days 7, 14, 21, time to pathogen eradication from baseline up to day 21 reported
Population: mITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gentamicin Sponge | Time to Baseline Pathogen Eradication | 7.0 Days |
| Levofloxacin | Time to Baseline Pathogen Eradication | 14.5 Days |
Secondary
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.
Time frame: Actual time assessed (Day 1, 3, 7 [14 and 21 if necessary] and Day 21 [or 28 or 35])
Population: Modified ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gentamicin Sponge | Time to Clinical Cure | 22.0 Days |
| Levofloxacin | Time to Clinical Cure | NA Days |
Secondary
Time to Pathogen Eradication
Time to Baseline Pathogen Eradication summed
Time frame: Actual time assessed (Day 1-21
Population: Micro Modified Intent-to-Treat Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gentamicin Sponge | Time to Pathogen Eradication | 7.0 Days |
| Levofloxacin | Time to Pathogen Eradication | 14.5 Days |
Secondary
Time to Positive Clinical Response
Time frame: (Day 1, 3, 7 [14 and 21 if necessary] and Day 21 [or 28 or 35])
Population: mITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gentamicin Sponge | Time to Positive Clinical Response | 2.0 Days |
| Levofloxacin | Time to Positive Clinical Response | 3.0 Days |