Primary Objective:To determine the effect of the Topical Gentamicin-Collagen Sponge (gentamicin-sponge) in combination with systemic antibiotic therapy compared to placebo-sponge and no-sponge, both in combination with systemic antibiotic therapy on…
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
- Diabetic complications
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy variable is the percent of patients with a clinical
outcome of "clinical cure" at follow-up visist 1. (Clinical cure= Resolution of
all clinical signs and symptoms of infection).
Secondary outcome
* Percent of patients with both a clinical outcome of "clinical cure" and
"baseline pathogen eradication" at follow-up visit 1
* Percent of patients with re-infection
* Time (days) to a clinical outcome of "clinical cure"
* Percent of patients that have an amputation associated with the target ulcer
* Percent of patients with target ulcer closure at or before follow-up visit 2
* Time (days) to closure of the target ulcer
Background summary
Infected skin ulcerations in patients with diabetes mellitus can be
debilitating and may cause significant morbidity due to prolonged, more severe
infection difficulty in healing. Diabetic ulcers are responsible for frequent
health care visits, accounting for the largest number of diabetes-related
hospital days. A diabetic ulcer on the foot or lower extremity is a major
predictor of amputation. Coordinated patient management of the infected
diabetic ulcer, as well as treatment of any underlying metabolic abnormalities,
are required for successful healing of the ulcer.
A major predisposing factor for diabetic foot ulcers is foot sensory and motor
neuropathy which can result in a patient's inability to sense pain or warmth.
Another factor, peripheral vascular disease, causes diminished blood flow to
the foot; this can result in a lack of erythema or induration, which are the
visual cues of infection. These combined comorbidities make the diabetic foot
prone to repeat ulceration and infection with subsequent negative consequences.
Aggressive and early treatment is necessary to prevent the need for amputation.
Study objective
Primary Objective:
To determine the effect of the Topical Gentamicin-Collagen Sponge
(gentamicin-sponge) in combination with systemic antibiotic therapy compared
to placebo-sponge and no-sponge, both in combination with systemic antibiotic
therapy on diabetic patients' clinical outcome in the treatment of infected
foot ulcers.
Secondary Objectives:
To determine the effect of the genatmicin-sponge in combination with systemic
antibiotic therapy compared to placebo-sponge and no-sponge, both in
combination with systemic antibiotic therapy on microbiological outcome and
eradication of baseline ulcer pathogens.
To assess the safety and tolerability of the gentamicin-sponge in combination
with systemic antibiotic therapy.
Study design
This is a phase 3, randomized, controlled, blinded, multicenter study conducted
in 3 parallel cohorts of diabetic patients with at least 1 infected foot ulcer.
Patients will be randomized using an electronic randomization system to receive
1 of 3 study treatments; systemic antibiotic therapy and standard ulcer care
with either (A) daily application of a gentamicin-sponge, (B) daily application
of a placebo-sponge or (C) no-sponge, in the ratio 2:1:1. The investigator will
be blinded to the patient's treatment group assignment and patients randomized
to one of the 2 sponge groups will be blinded as to whether the sponge is
active or placebo.
If a patient has multiple infected ulcers, the assigned treatment will be
administered to all infected ulcers. The investigator will determine the
highest severity ulcer to be used for all efficacy evaluations and will also
determine the size and number of sponges (up to 4) that a patient will use in
order to completely cover all infected ulcers. The investigator will prescribe
an empiric systemic antibiotic therapy based on protocol instructions.
Patients will be treated for approximately 28 days and return to the clinic
weekly for safety and efficacy assessments. The investigator will stop study
treatment if a patient achieves clinical cure by or after the 3rd treatment
visit (approximately study day 15). After completing treatment, patients will
return to the clinic for scheduled follow-up visits or until ulcer closure. The
final efficacy assessments used in the primary efficacy analyses will be
obtained at the first follow-up visit approximately 10 days after treatment is
stopped. The remaining follow-up visits will occur at approximately 30, 60 and
90 days after treatment is stopped when patients will be assessed for ulcer
closure and any re-infection.
Intervention
Cohort A: The appropriate size and number of gentamicin-sponges to each
infected ulcer on a daily basis, systemic antibiotic therapy as prescribed and
standard ulcer care (= gentamicin-sponge group)
Cohort B: The appropriate size and number of placebo-sponges to each infected
ulcer on a daily basis, systemic antibiotic therapy as prescribed and standard
ulcer care (= placebo-sponge group)
Cohort C: Systemic antibiotic therapy as prescribed
Study burden and risks
Risks: possible side effects of the study medication
Burden:
* 9 visits at the study center
* at 6 of 9 visits: collection of urine and blood samples
* at 6 of 9 visits: assessment of the ulcer and (if deemed necessary) ulcer
débridement
* at 3 of 9 visits: collection of a culture of the ulcer
* at 5 of 9 visits: a full physical examination will be performed
Patients need to fill out a patient worksheet/diary on a daily basis.
Block D Monksland Business park, Monksland Unit 9
Athlone Co. Roscommon
IE
Block D Monksland Business park, Monksland Unit 9
Athlone Co. Roscommon
IE
Listed location countries
Age
Inclusion criteria
1. Is aged >= 18 and <= 85 years.
2. Has diabetes mellitus, according to the American Diabetes Association (ADA) criteria.
3. Has at least 1 skin ulcer located on or below the malleolus that presents with the following clinical manifestations of a moderate or severe infection based on the Infectious Disease Society of America guidelines for the *Diagnosis and Treatment of Diabetic Foot Infections* (CID 2012; 54:132-173) (IDSA guidelines):
• has >= 2 manifestations of inflammation (local swelling or induration, erythema, local tenderness or pain, local warmth, purulent discharge (thick, opaque to white or sanguineous secretion)
• has >= 1 of the following characteristics: erythema > 2cm, or involving structures deeper than skin and subcutaneous tissues (e.g. abscess, osteomyelitis, septic arthritis, fasciitis)
For patients with multiple infected ulcers, the ulcer with the highest Diabetic Foot Infection Wound score (DFI score) must be on or below the malleolus and all infected ulcers must be completely coverable using no more than 4 sponges (sponges cannot be cut).
4. Has documented adequate arterial perfusion in the affected limb(s) (either palpable dorsalis pedis and posterior tibial pulses, or normal Doppler wave forms, a toe blood pressure >= 45 mm Hg or participation is approved by a vascular surgeon);
5. Has received appropriate surgical intervention to remove all necrotic and infected bone if diagnosed with osteomyelitis. [Note: The investigator is referred to Diabetes Metab Res Rev 2008; 24(Suppl 1): S145-S161 for recommendations for the diagnosis of diabetic foot osteomyelitis.]
6. Has received appropriate surgical debridement to remove all gangrenous tissue.
7. If female, is nonpregnant (negative pregnancy test results at the baseline/randomization visit) and nonlactating.
8. 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).
9. Is willing and able to return to the study facility for all follow-up visits.
10. Is able to fluently speak and understand the local language and is able to provide meaningful written informed consent for the study.
Once baseline clinical laboratory results become available, a patient will continue to be eligible for study participation after enrollment if he or she meets the following criteria:
11. Has the following laboratory values
• white blood cells (WBC) >= 4000 cells/mm3 and/or absolute neutrophil count (ANC) >= 1500 cells/mm3
• hematocrit > 25%,
• hemoglobin > 8 g/L,
• platelet count >75 000/mm3
• coagulation test results less than 1.5 times the upper limit of normal (unless on anticoagulant therapy).
Any subject whose baseline laboratory results fall outside of these parameters will be withdrawn from the study.
Exclusion criteria
1. Has a known history of hypersensitivity to gentamicin (or other aminoglycosides).
2. Has a known or suspected hypersensitivity to bovine collagen.
3. Has an ulcer infection which, based upon the patient*s known history of hypersensitivity and/or as otherwise in the opinion of the investigator, cannot be adequately treated with at least one of the empiric systemic antibiotic regimens allowed by this protocol.
4. Has an ulcer associated with prosthetic material or an implanted device.
5. Has received any systemic or topical antibiotic therapy for any reason within 7 days of randomization unless it was administered to specifically treat the infected ulcer(s) and only within 36 hours of randomization.
6. Requires or is likely to require treatment with any concomitant topical product or wound therapy before the first follow-up study visit.
7. Is severely immunocompromised, or likely to become severely immunocompromised during the study, in the opinion of the investigator.
8. Has a history of myasthenia gravis or other neurological condition where gentamicin use is contraindicated as determined by the investigator.
9. Has a history of epilepsy.
10. Has a history of alcohol or substance abuse in the past 12 months.
11. Has an uncontrolled illness that, in the opinion of the investigator, is likely to cause the patient to be withdrawn from the trial or would otherwise interfere with interpreting the results of the study.
12. Has a known history of severe renal impairment or has a creatinine clearance <= 30 mL/min at
Visit 1/Day 1.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-000934-31-NL |
| CCMO | NL53797.091.15 |