Clinical trial NCT02447172: Study of a Topical Gentamicin-Collagen Sponge Along With Systemic Antibiotic in Infected Diabetic Foot Ulcers
Official title: A Phase 3 Randomized, Placebo-Controlled, Blinded Study to Investigate the Safety and Efficacy of a Topical Gentamicin-Collagen Sponge in Combination With Systemic Antibiotic Therapy in Diabetic Patients With an Infected Foot Ulcer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Foot Ulcer, Diabetic
Infection
Lead sponsor: Innocoll
Sponsor class: INDUSTRY
First posted: 2015-05-18
Enrollment: 524
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 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. Patients will be treated for approximately 28 days and return to the clinic weekly for safety and efficacy assessments. After completing treatment, patients will return to the clinic for scheduled follow-up visits approximately 10, 30, 60 and 90 days after treatment is stopped.

Detailed description: 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.

Eligibility criteria: * Has diabetes mellitus, according to the American Diabetes Association (ADA) criteria.
* 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).
* 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)
* Has received appropriate surgical intervention to remove all necrotic and infected bone if diagnosed with osteomyelitis.
* Has received appropriate surgical debridement to remove all gangrenous tissue.

Exclusion Criteria:

Has a known history of hypersensitivity to gentamicin (or other aminoglycosides).

* Has a known or suspected hypersensitivity to bovine collagen.
* 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.
* Has an ulcer associated with prosthetic material or an implanted device.
* 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.
* Requires or is likely to require treatment with any concomitant topical product or wound therapy before the first follow-up study visit.
* Is severely immunocompromised, or likely to become severely immunocompromised during the study, in the opinion of the investigator.
* 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 alcohol or substance abuse in the past 12 months.
* 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

Primary outcomes:
measure: Percent of Patients With a Clinical Outcome of Clinical Cure (Resolution of All Clinical Signs and Symptoms of Infection)
timeFrame: approximately 10 days after end of treatment
Secondary outcomes:
measure: Number of Patients With Re-infections
timeFrame: up to 90 days after treatment stopped
measure: Time to Clinical Response
timeFrame: up to 90 days after treatment stopped
measure: Percent of Subjects That Had an Amputation Associated With the Target Ulcer
timeFrame: up to 90 days after treatment stopped
Other outcomes:
Locations:
city: Anniston
country: United States
state: Alabama
city: Las Vegas
country: United States
state: Nevada
city: Cowra
country: Australia
state: New South Wales
city: Spring Hill
country: Australia
state: Queensland
city: Graz
country: Austria
state: Styria
city: Vienna
country: Austria
city: Vienna
country: Austria
city: Brussels
country: Belgium
city: Edegem
country: Belgium
city: Kortrijk
country: Belgium
city: Liége
country: Belgium
city: Pellenberg
country: Belgium
city: Brno
country: Czechia
city: Pardubice
country: Czechia
city: Praha 10
country: Czechia
city: Praha 2
country: Czechia
city: Praha 4
country: Czechia
city: Praha 6
country: Czechia
city: Třinec
country: Czechia
city: Zlín
country: Czechia
city: Hillerød
country: Denmark
city: København
country: Denmark
city: Bad Mergentheim
country: Germany
state: Baden-Württemberg
city: Aschaffenburg
country: Germany
state: Bayern
city: Fulda
country: Germany
state: Hessen
city: Dortmund
country: Germany
state: Nordrhein-Westfalen
city: Duisburg
country: Germany
state: Nordrhein-Westfalen
city: Münster
country: Germany
state: Nordrhein-Westfalen
city: Bosenheim
country: Germany
state: Reinland-Pfalz
city: Dresden
country: Germany
state: Sachsen
city: Pirna
country: Germany
state: Sachsen
city: Berlin
country: Germany
city: Debrecen
country: Hungary
city: Hatvan
country: Hungary
city: Orosháza
country: Hungary
city: Szekszárd
country: Hungary
city: Székesfehérvár
country: Hungary
city: Sátoraljaújhely
country: Hungary
city: Waterford
country: Ireland
city: Campobasso
country: Italy
state: CB
city: Abano Terme
country: Italy
state: PD
city: Pistoia
country: Italy
state: Point
city: Pavia
country: Italy
state: PV
city: Bassano del Grappa
country: Italy
state: VI
city: Almere
country: Netherlands
city: Eindhoven
country: Netherlands
city: Maastricht
country: Netherlands
city: Nijmegen
country: Netherlands
city: Nijmegen
country: Netherlands
city: the Hague
country: Netherlands
city: Utrecht
country: Netherlands
city: Wrocław
country: Poland
state: Lower Silesia
city: Chorzow
country: Poland
city: Czestochowa
country: Poland
city: Gdańsk
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Poznań
country: Poland
city: Studzionka
country: Poland
city: Warszawa
country: Poland
city: Zabrze
country: Poland
city: Bratislava
country: Slovakia
city: Bratislava
country: Slovakia
city: Nitra
country: Slovakia
city: Trenćín
country: Slovakia
city: Trnava
country: Slovakia
city: Ľubochňa
country: Slovakia
city: Badalona
country: Spain
state: Barcelona
city: San Sebastian
country: Spain
state: Gipuzkoa
city: Alcorcon
country: Spain
state: Madrid
city: Manises
country: Spain
state: Valencia
city: Girona
country: Spain
city: Lleida
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Linköping
country: Sweden
city: Lund
country: Sweden
city: Stockholm
country: Sweden
city: Bradford
country: United Kingdom
city: Bristol
country: United Kingdom
city: Burton on Trent
country: United Kingdom
city: Coventry
country: United Kingdom
city: Derby
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Lancaster
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Merthyr
country: United Kingdom
city: Stoke-on-Trent
country: United Kingdom
Study officials:
affiliation: Vice President, Global Clinical Operations, Innocoll Pharmaceutical
name: Nigel Jones
role: STUDY_DIRECTOR
References: