Autologous Skin Substitute for Chronic Leg/Foot Ulcers.
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: autologous cultured skin autologous cultured skin patches (Tiscover) is applied on wound in 2-step procedure with 1 week interval. Dosage: number of patches depends on wound size. Application week 0 is removed after one week (week1). Week 1: wound is completely covered with new Tiscover patches. |
Drug: Tiscover
two step procedure, week 0 and week1. Dosage depends on wound size.
Other Names:
|
| Active Comparator: acellular donor dermis acellular donor dermis (AS210) is applied on wound in 2-step procedure with 1 week interval. Dosage: number of patches depends on wound size. Application week 0 is removed after one week (week1). Week 1: wound is completely covered with new AS210 patches. |
Other: AS210
two step procedure, week 0 and week1. Dosage depends on wound size.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of subjects with complete wound closure after 26 weeks. [26 weeks]
The primary objective of this study is to demonstrate the superiority of Tiscover® compared to AS210 for achieving wound healing in subjects with a chronic (arterio) venous leg or foot ulcer.
Secondary Outcome Measures
- Time in days to complete wound closure from baseline. [12 weeks]
- • Proportion of subjects with complete wound closure at each of the 12 treatment weeks. [12 weeks]
- Percentage of wound closure [12 and 26 weeks]
- Proportion of subjects with durable wound healing over the 3 months following complete wound closure [3 months and 6 months follow up]
- Wound size reduction [12 and 26 weeks]
The percentage of reduction in wound area
- Pain [week 0, 1,2,4,8,12, 26 weeks and follow up]
Measured with VAS Pain scale
- Quality of Life [Week 0, 12, 26 weeks and follow up]
Measured with SF 36
- Number of SAE [12, 26 weeks and follow up]
Eligibility Criteria
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)
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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.
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Therapy with another investigational agent within thirty (30) days of Screening, or during the study.
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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.
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Refusal of or inability to tolerate compression therapy.
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Therapy of the target ulcer with autologous skin graft, Apligraf™, or Dermagraft™ within 30 days preceding the Screening Visit.
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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
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Presence of deep vein thrombosis or contra indication for compression therapy
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Severe co-morbidity reducing life expectance to < 1 year
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Use of oral corticosteroids and/or cytostatics >20 mg/per day;
-
Severe infection of ulcer, active cellulitis, osteomyelitis
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Severe malnutrition
-
Uncontrolled diabetes mellitus, HbA1c > 12% (108 mmol/mol)
-
Anaemia Hb <6 mmol/l
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centrum Oosterwal | Alkmaar | Netherlands | 1817 MS | |
| 2 | Flevo Ziekenhuis, afdeling dermatologie | Almere | Netherlands | ||
| 3 | VU University Medical center | Amsterdam | Netherlands | 1081HZ | |
| 4 | St. Fransiscus Gasthuis | Rotterdam | Netherlands | ||
| 5 | Isala Ziekenhuis, dermatologie | Zwolle | Netherlands |
Sponsors and Collaborators
- Chantal Blok
- ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
- Study Chair: Susan Gibss, Prof.dr., VU medical center, department of dermatology
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TIS2012