Autologous Skin Substitute for Chronic Leg/Foot Ulcers.
Primary Purpose
Varicose Ulcer
Status
Terminated
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Tiscover
AS210
Sponsored by
About this trial
This is an interventional treatment trial for Varicose Ulcer
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
Sites / Locations
- Centrum Oosterwal
- Flevo Ziekenhuis, afdeling dermatologie
- VU University Medical center
- St. Fransiscus Gasthuis
- Isala Ziekenhuis, dermatologie
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
autologous cultured skin
acellular donor dermis
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Proportion of subjects with complete wound closure after 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.
• Proportion of subjects with complete wound closure at each of the 12 treatment weeks.
Percentage of wound closure
Proportion of subjects with durable wound healing over the 3 months following complete wound closure
Wound size reduction
The percentage of reduction in wound area
Pain
Measured with VAS Pain scale
Quality of Life
Measured with SF 36
Number of SAE
Full Information
NCT ID
NCT02360358
First Posted
January 29, 2015
Last Updated
January 6, 2016
Sponsor
Chantal Blok
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development
1. Study Identification
Unique Protocol Identification Number
NCT02360358
Brief Title
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
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Terminated
Why Stopped
slow inclusion
Study Start Date
August 2012 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Chantal Blok
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Varicose Ulcer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
autologous cultured skin
Arm Type
Experimental
Arm Description
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.
Arm Title
acellular donor dermis
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tiscover
Other Intervention Name(s)
autologous skin substitute
Intervention Description
two step procedure, week 0 and week1. Dosage depends on wound size.
Intervention Type
Other
Intervention Name(s)
AS210
Other Intervention Name(s)
Acellular donor dermis
Intervention Description
two step procedure, week 0 and week1. Dosage depends on wound size.
Primary Outcome Measure Information:
Title
Proportion of subjects with complete wound closure after 26 weeks.
Description
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.
Time Frame
26 weeks
Secondary Outcome Measure Information:
Title
Time in days to complete wound closure from baseline.
Time Frame
12 weeks
Title
• Proportion of subjects with complete wound closure at each of the 12 treatment weeks.
Time Frame
12 weeks
Title
Percentage of wound closure
Time Frame
12 and 26 weeks
Title
Proportion of subjects with durable wound healing over the 3 months following complete wound closure
Time Frame
3 months and 6 months follow up
Title
Wound size reduction
Description
The percentage of reduction in wound area
Time Frame
12 and 26 weeks
Title
Pain
Description
Measured with VAS Pain scale
Time Frame
week 0, 1,2,4,8,12, 26 weeks and follow up
Title
Quality of Life
Description
Measured with SF 36
Time Frame
Week 0, 12, 26 weeks and follow up
Title
Number of SAE
Time Frame
12, 26 weeks and follow up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan Gibss, Prof.dr.
Organizational Affiliation
VU medical center, department of dermatology
Official's Role
Study Chair
Facility Information:
Facility Name
Centrum Oosterwal
City
Alkmaar
ZIP/Postal Code
1817 MS
Country
Netherlands
Facility Name
Flevo Ziekenhuis, afdeling dermatologie
City
Almere
Country
Netherlands
Facility Name
VU University Medical center
City
Amsterdam
ZIP/Postal Code
1081HZ
Country
Netherlands
Facility Name
St. Fransiscus Gasthuis
City
Rotterdam
Country
Netherlands
Facility Name
Isala Ziekenhuis, dermatologie
City
Zwolle
Country
Netherlands
12. IPD Sharing Statement
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Autologous Skin Substitute for Chronic Leg/Foot Ulcers.
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