Autologous Skin Substitute for Chronic Leg/Foot Ulcers.

• ClinicalTrials.gov Identifier: NCT02360358
• Recruitment Status: Terminated
• First Posted: February 10, 2015
• Last Update Posted: January 7, 2016
• Sponsor: Chantal Blok
• Collaborator: ZonMw: The Netherlands Organisation for Health Research and Development
• Information provided by (Responsible Party): Chantal Blok, VU University Medical Center

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
Varicose Ulcer	Drug: Tiscover; Other: AS210	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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: August 2012
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: December 2015

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 Name: autologous skin substitute
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 Name: Acellular donor dermis

Outcome Measures

Primary Outcome Measures :

1. Proportion of subjects with complete wound closure after 26 weeks. [ Time Frame: 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 :

1. Time in days to complete wound closure from baseline. [ Time Frame: 12 weeks ]
2. • Proportion of subjects with complete wound closure at each of the 12 treatment weeks. [ Time Frame: 12 weeks ]
3. Percentage of wound closure [ Time Frame: 12 and 26 weeks ]
4. Proportion of subjects with durable wound healing over the 3 months following complete wound closure [ Time Frame: 3 months and 6 months follow up ]
5. Wound size reduction [ Time Frame: 12 and 26 weeks ]
   The percentage of reduction in wound area
6. Pain [ Time Frame: week 0, 1,2,4,8,12, 26 weeks and follow up ]
   Measured with VAS Pain scale
7. Quality of Life [ Time Frame: Week 0, 12, 26 weeks and follow up ]
   Measured with SF 36
8. Number of SAE [ Time Frame: 12, 26 weeks and follow up ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Netherlands

Centrum Oosterwal

Alkmaar, Netherlands, 1817 MS

Flevo Ziekenhuis, afdeling dermatologie

Almere, Netherlands

VU University Medical center

Amsterdam, Netherlands, 1081HZ

St. Fransiscus Gasthuis

Rotterdam, Netherlands

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

More Information

• Responsible Party: Chantal Blok, trial coordinator, VU University Medical Center
• ClinicalTrials.gov Identifier: NCT02360358
• Other Study ID Numbers: TIS2012
• First Posted: February 10, 2015
• Last Update Posted: January 7, 2016
• Last Verified: January 2016

Additional relevant MeSH terms:

Varicose Ulcer; Ulcer; Pathologic Processes; Varicose Veins; Vascular Diseases; Cardiovascular Diseases; Leg Ulcer; Skin Ulcer; Skin Diseases