Clinical trial NCT02360358: Autologous Skin Substitute for Chronic Leg/Foot Ulcers.
Official title: A Phase II Randomized Multicenter Study on Efficacy and Safety of Cultured Autologous Skin (Tiscover®) and Acellular Dermal Matrix (AS210) in Chronic (Arterio-)Venous Ulcers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Varicose Ulcer
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2015-02-10
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A prospective, multicenter, randomised controlled phase II study in which patients with therapy resistant (arterio-) venous leg/foot ulcers are treated with Tiscover® (test group) or with AS210 (control group) to determine the safety and relative efficacy of both products.

Detailed description: Multicenter, randomised clinical trial in out patient in which patients with chronic (arterio-) venous leg/foot ulcers are treated with an autologous cultured human living skin substitute (Tiscover®: test group) or with Acellular donor dermis (AS210: control group). During a pre-inclusion evaluation period of 4 weeks (non healing) chronicity of ulcer is ensured (ulcer size change of \< 30%). To determine ulcer type ABI, Doppler and CEAP is performed.

The test group will receive 2 applications of Tiscover®. Week 0: wound activating pre-treatment, application of at least one quarter of the wound surface. Week 1: removal of patches, application of patches on total wound surface.

The control group (16 patients) will follow the same application protocol.

Eligibility criteria: Inclusion criteria:

* Have a (arterio) venous leg ulcer (VLU) between the knee and ankle (at or above the malleolus), or on foot (not plantar side of the foot) with a surface area ≥ 1.0 cm2 and ≤ 40.0 cm2
* Venous insufficiency confirmed by duplex Doppler ultrasound examination for valvular or venous incompetence.
* Arterial supply adequacy confirmed (ABPI ≥ 0.6 and ≤ 1.3)
* Target ulcer involves a full thickness skin loss, but WITHOUT exposure of tendon, muscle, or bone. Ulcer depth \< 1 cm
* Target ulcer duration ≥ 12 weeks but ≤ 15 years
* Acceptable state of health and nutrition
* Mobile, at least able to walk with medical walker, and able to return for required treatments and study evaluations

Exclusion Criteria:

* History of anaphylaxis, serum sickness, or erythema multiforme reaction to bovine serum proteins, gentamycin.
* Therapy with another investigational agent within thirty (30) days of Screening, or during the study.
* A target ulcer of non-venous etiologies (e.g., sickle cell anemia, necrobiosis lipoidica diabeticorum, pyoderma gangrenosum, vasculopathic or vasculitic).
* Documented history of osteomyelitis at the target wound location within 6 months preceding the Screening Visit.
* Refusal of or inability to tolerate compression therapy.
* Therapy of the target ulcer with autologous skin graft, Apligraf™, or Dermagraft™ within 30 days preceding the Screening Visit.
* History of cancer in the preceding 5 years (other than carcinoma in situ of the cervix or adequately treated non-melanoma skin cancers).
* \>30% change of wound size in 4 weeks or confirmed by historical data
* Presence of deep vein thrombosis or contra indication for compression therapy
* Severe co-morbidity reducing life expectance to \< 1 year
* Use of oral corticosteroids and/or cytostatics \>20 mg/per day;
* Severe infection of ulcer, active cellulitis, osteomyelitis
* Severe malnutrition
* Uncontrolled diabetes mellitus, HbA1c \> 12% (108 mmol/mol)
* Anaemia Hb \<6 mmol/l

Primary outcomes:
measure: Proportion of subjects with complete wound closure after 26 weeks.
timeFrame: 26 weeks
Secondary outcomes:
measure: Time in days to complete wound closure from baseline.
timeFrame: 12 weeks
measure: • Proportion of subjects with complete wound closure at each of the 12 treatment weeks.
timeFrame: 12 weeks
measure: Percentage of wound closure
timeFrame: 12 and 26 weeks
measure: Proportion of subjects with durable wound healing over the 3 months following complete wound closure
timeFrame: 3 months and 6 months follow up
measure: Wound size reduction
timeFrame: 12 and 26 weeks
measure: Pain
timeFrame: week 0, 1,2,4,8,12, 26 weeks and follow up
measure: Quality of Life
timeFrame: Week 0, 12, 26 weeks and follow up
measure: Number of SAE
timeFrame: 12, 26 weeks and follow up
Other outcomes:
Locations:
city: Alkmaar
country: Netherlands
facility: Centrum Oosterwal
city: Almere
country: Netherlands
facility: Flevo Ziekenhuis, afdeling dermatologie
city: Amsterdam
country: Netherlands
facility: VU University Medical center
city: Rotterdam
country: Netherlands
facility: St. Fransiscus Gasthuis
city: Zwolle
country: Netherlands
facility: Isala Ziekenhuis, dermatologie
Study officials:
affiliation: VU medical center, department of dermatology
name: Susan Gibss, Prof.dr.
role: STUDY_CHAIR
References: