Back to resultsOleogel-S10 in Wound Healing of Split-Thickness Skin Graft Donor Sites (BSH-12)
Primary Purpose
Wounds
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Oleogel-S10, non-adhesive wound dressing
Non-adhesive wound dressing only
Sponsored by
About this trial
This is an interventional treatment trial for Wounds focused on measuring Split-Thickness Skin Graft (STSG) donor site, Split-thickness skin graft, STSG, Wound healing, Skin grafting, Superficial wound, Partial-thickness wound, Time to wound closure
Eligibility Criteria
Inclusion Criteria:
- Presenting a split-thickness skin graft donor site wound with a minimum size of 15 cm2 and with a minimum width of 3 cm.
- Patient is able to understand the Informed Consent Form (ICF) provided and is prepared to comply with all study requirements, including the following: Visiting the trial site for wound dressing change and photo documentation every third or fourth day until both wound halves are closed (but no longer than 28 days after surgery).
- Willing to perform all necessary wound dressing changes at the trial site. Also the patient needs to agree to return to site for 3 and 12 months follow-up visits.
- Women of childbearing potential must apply highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly (e.g., implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices (IUDs), sexual abstinence, or a vasectomized partner)).
Exclusion Criteria:
- Diseases or conditions that could, in the opinion of the Investigator, interfere with the assessment of safety or efficacy.
- A skin disorder that is chronic or currently active and which the Investigator considers will adversely affect the healing of the acute wounds or involves the areas to be examined in this trial.
- A history of clinically significant hypersensitivity to any of the drugs, surgical dressings or excipients to be used in this trial.
- Known multiple allergic disorders.
- Taking, or have taken, any investigational drugs within 3 months prior to the screening visit.
- Pregnant or breast feeding women are not allowed to participate in the study.
- Inappropriate to participate in the study, for any reason, in the opinion of the investigator.
- Mental incapacity or language barriers precluding adequate understanding the Informed consent form or co-operation or willingness to follow study procedures.
- Previous participation in this study.
- Employee at the investigational site, relative or spouse of the investigator.
Sites / Locations
- Medical University of Graz
- Landesklinik für Dermatologie
- Medical University Vienna
- University Multiprofile Hospital for Active Treatment-"Dr. Georgi Stranski" EAD
- University Multiprofile Hospital for Active Treatment "Saint George"
- Multiprofile Hospital for Active Treatment- Ruse
- University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I.Pirogov"
- University Multiprofile Hospital for Active Treatment-Varna at MMA-Sofia
- Universtity Hospital Brno
- University Hospital Olomouc
- Päijät-Hämeen keskussairaala
- Satakunnan keskussairaala
- Trauma Hospital
- University Hospital
- Essen University Hospital
- University Hospital
- University Medical Center
- University Medicine Greifswald
- HELIOS Clinic
- University Medical Center
- Klinikum rechts der Isar
- Klinikum Offenbach am Main
- Univesity Hospital Gdansk
- Samodzelny Publiczny Szpital Kliniczny Nr. 1
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Oleogel-S10, non-adhesive wound dressing
Non-adhesive wound dressing only
Arm Description
A split-thickness skin graft (STSG) donor site wound >15cm2 in size was divided in 2 halves. One half was randomized to Oleogel-S10 treatment and non-adhesive wound dressing (intra-individual comparison). Oleogel-S10 was administered (1 cm or 100 mg per cm2 wound area corresponding to thickness of about 1 mm or 0.04 inch) every 3 to 4 days until 95% epithelialization of the wound or end of treatment at Day 28.
A STSG donor site wound >15cm2 in size was divided in 2 halves. One half was randomized to treatment with non-adhesive wound dressing only (intra-individual comparison). Non-adhesive wound dressings are standard of care (SOC) in the treatment of STSG donor sites. Wound dressings were changed every 3 to 4 days until 95% epithelialization of the wound or end of treatment at Day 28.
Outcomes
Primary Outcome Measures
Intra-individual Difference in Time to Wound Closure
Intra-individual difference in time to wound closure between wound halves, either treated with Oleogel-S10 and non-adhesive wound dressing or treated with non-adhesive wound dressing only. Independent experts were blind to treatment and assessed efficacy based on chronological series of cropped and coded photographs by wound half that were taken before start of treatment, during wound dressing changes and at the end of treatment. Difference in time to wound closure was calculated for every individual participant as [time taken for wound half treated with Oleogel-S10 to close] - [time taken for wound half treated with non-adhesive wound dressing to close], i.e., results below 0 indicate earlier wound closure of Oleogel-S10 treatment. The overall mean difference in time to wound closure was calculated based on all mean differences in time to wound closure of individual participants. Hence, primary outcome data derived from mean difference in time to wound closure by participant.
Secondary Outcome Measures
Time From Surgery Until Wound Closure is Achieved
Time from surgery until wound closure is achieved, separately for wound halves treated with Oleogel-S10 and non-adhesive wound dressing vs. non-adhesive wound dressing only. While outcome measure 1 (intra-individual difference in time to wound closure) was calculated based on mean intra-individual difference in time to wound closure in 107 participants with missing values replaced by a value of 0, for outcome measure 2 missing values were not replaced. For 5 of the 107 wounds data were missing, thus the reported values are calculated from 102 STSG donor site wound halves by intervention (Oleogel-S10 and non-adhesive wound dressing vs. non-adhesive wound dressing only).
Percentage of Participants With Earlier Healing
Percentage of participants with earlier healing of wound area treated with Oleogel-S10 and non-adhesive wound dressing compared to non-adhesive wound dressing only
Percentage of Participants With Wound Closure at Different Time Points
For separate time points (Day 7, Day 10, Day 14, Day 18, Day 21, and Day 28), the frequencies of wound areas which have reached wound closure were calculated.
Percentage of Wound Epithelialization at Different Time Points as Assessed by the Investigator
A study team member assessed the progress of wound healing by treatment regimen and noted the degree of epithelialization (expressed in percent of the original wound size) at wound dressing changes on Day 7, Day 10, Day 14, Day 18, Day 21, and Day 28.
Likert Scale Rating of Efficacy
Participants and investigators were asked to grade the efficacy of Oleogel-S10 and non-adhesive wound dressing versus non-adhesive wound dressing only on a 5-point Likert scale (treatment with Oleogel-S10 is much more effective, treatment with Oleogel-S10 is more effective, both treatments have the same efficacy, non-adhesive wound dressing only is more effective, non-adhesive wound dressing only is much more effective).
Cosmetic Outcome at 3 and 12 Months After Surgery, Respectively
Blinded photographic evaluation which wound half resembles more closely the surrounding skin with regard to texture, redness, growth of hair, and pigmentation.
Likert Scale Rating of Tolerability
Participants and investigators were asked to evaluate the tolerability of Oleogel-S10 and non-adhesive wound dressing versus non-adhesive wound dressing only (standard of care) on a 5-point Likert scale (treatment with Oleogel-S10 is much better tolerated, treatment with Oleogel-S10 is better tolerated, both treatments are equally well tolerated, standard of care is better tolerated, standard of care is much better tolerated).
Pharmacokinetic (PK) Data (Number of Plasma Samples With Measurable Betulin Concentration)
Systemic presence/concentration of betulin in blood plasma samples. Plasma samples were collected in weekly intervals and at the end of treatment (when wound closure was achieved or at Day 28). Samples were analysed in a central laboratory with a validated LC-MS/MS method with a lower limit of quantification (LLOQ) of 1 ng/mL.
Pharmacokinetic (PK) Data (Plasma Betulin Concentration)
Systemic presence/concentration of betulin in blood plasma samples - values for the number of samples with measurable values in samples above the lower limit of quantification (LLOQ) of 1 ng/mL
Frequency of Adverse Events
Severity of Adverse Events
Adverse Events were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) as being mild (NCI CTCAE Grade 1), moderate (NCI CTCAE Grade 2), severe (NCI CTCAE Grade 3), life-threatening (NCI CTCAE Grade 4) or death (NCI CTCAE Grade 5).
Adverse Events by Relationship to Study Medication
Adverse events were assessed as being 'unlikely', 'possibly' or 'probably' related to study medication, 'not related' to study medication or the relationship to study medication was rated as 'unknown'.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01657305
Brief Title
Oleogel-S10 in Wound Healing of Split-Thickness Skin Graft Donor Sites (BSH-12)
Official Title
Open, Blindly Evaluated, Prospective, Controlled, Randomized, Multicenter Phase III Clinical Trial to Compare Intra-individually the Efficacy and Tolerance of Oleogel-S10 Versus Standard of Care in Accelerating the Wound Healing of Split-Thickness Skin Graft Donor Sites
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
September 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Birken AG
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main purpose of this phase III clinical trial was to compare intra-individually the efficacy, safety and tolerability of Oleogel-S10 and non-adhesive wound dressing versus non-adhesive wound dressing only in accelerating the wound healing of Split-Thickness Skin Graft (STSG) donor sites.
Detailed Description
Oleogel-S10 has shown efficacy and was well tolerated in previous clinical trials in participants with skin lesions. Especially the results in a previous study with STSG donor sites suggested that Oleogel-S10 should be efficacious and safe in the treatment of superficial wounds.
The present phase III clinical trial in STSG donor sites was initiated to demonstrate wound healing progress, i.e., the time to healing and the grade of epithelialization of the wound.
In this study, STSG donor sites were separated into 2 wound halves. Randomly assigned, 1 wound half was treated with Oleogel-S10 and non-adhesive wound dressing, the other wound half with non-adhesive wound dressing only (standard of care).
Wound healing progress was documented by photos which were assessed by expert reviewers blind to the treatment of the wound halves.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wounds
Keywords
Split-Thickness Skin Graft (STSG) donor site, Split-thickness skin graft, STSG, Wound healing, Skin grafting, Superficial wound, Partial-thickness wound, Time to wound closure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
107 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Oleogel-S10, non-adhesive wound dressing
Arm Type
Experimental
Arm Description
A split-thickness skin graft (STSG) donor site wound >15cm2 in size was divided in 2 halves. One half was randomized to Oleogel-S10 treatment and non-adhesive wound dressing (intra-individual comparison). Oleogel-S10 was administered (1 cm or 100 mg per cm2 wound area corresponding to thickness of about 1 mm or 0.04 inch) every 3 to 4 days until 95% epithelialization of the wound or end of treatment at Day 28.
Arm Title
Non-adhesive wound dressing only
Arm Type
Other
Arm Description
A STSG donor site wound >15cm2 in size was divided in 2 halves. One half was randomized to treatment with non-adhesive wound dressing only (intra-individual comparison). Non-adhesive wound dressings are standard of care (SOC) in the treatment of STSG donor sites. Wound dressings were changed every 3 to 4 days until 95% epithelialization of the wound or end of treatment at Day 28.
Intervention Type
Drug
Intervention Name(s)
Oleogel-S10, non-adhesive wound dressing
Other Intervention Name(s)
Episalvan®
Intervention Description
1 cm or 100 mg Oleogel-S10 per cm2 wound area (corresponds to thickness of approximately 1 mm or 0.04 inch) every 3 to 4 days until 95% epithelialization of the wound or end of treatment at Day 28.
Intervention Type
Device
Intervention Name(s)
Non-adhesive wound dressing only
Other Intervention Name(s)
Mepilex®
Intervention Description
Soft silicone faced polyurethane foam dressing such as Mepilex® only every 3 to 4 days until 95% epithelialization of the wound or end of treatment at Day 28.
Primary Outcome Measure Information:
Title
Intra-individual Difference in Time to Wound Closure
Description
Intra-individual difference in time to wound closure between wound halves, either treated with Oleogel-S10 and non-adhesive wound dressing or treated with non-adhesive wound dressing only. Independent experts were blind to treatment and assessed efficacy based on chronological series of cropped and coded photographs by wound half that were taken before start of treatment, during wound dressing changes and at the end of treatment. Difference in time to wound closure was calculated for every individual participant as [time taken for wound half treated with Oleogel-S10 to close] - [time taken for wound half treated with non-adhesive wound dressing to close], i.e., results below 0 indicate earlier wound closure of Oleogel-S10 treatment. The overall mean difference in time to wound closure was calculated based on all mean differences in time to wound closure of individual participants. Hence, primary outcome data derived from mean difference in time to wound closure by participant.
Time Frame
up to 4 weeks
Secondary Outcome Measure Information:
Title
Time From Surgery Until Wound Closure is Achieved
Description
Time from surgery until wound closure is achieved, separately for wound halves treated with Oleogel-S10 and non-adhesive wound dressing vs. non-adhesive wound dressing only. While outcome measure 1 (intra-individual difference in time to wound closure) was calculated based on mean intra-individual difference in time to wound closure in 107 participants with missing values replaced by a value of 0, for outcome measure 2 missing values were not replaced. For 5 of the 107 wounds data were missing, thus the reported values are calculated from 102 STSG donor site wound halves by intervention (Oleogel-S10 and non-adhesive wound dressing vs. non-adhesive wound dressing only).
Time Frame
up to 4 weeks
Title
Percentage of Participants With Earlier Healing
Description
Percentage of participants with earlier healing of wound area treated with Oleogel-S10 and non-adhesive wound dressing compared to non-adhesive wound dressing only
Time Frame
up to 4 weeks
Title
Percentage of Participants With Wound Closure at Different Time Points
Description
For separate time points (Day 7, Day 10, Day 14, Day 18, Day 21, and Day 28), the frequencies of wound areas which have reached wound closure were calculated.
Time Frame
up to 4 weeks
Title
Percentage of Wound Epithelialization at Different Time Points as Assessed by the Investigator
Description
A study team member assessed the progress of wound healing by treatment regimen and noted the degree of epithelialization (expressed in percent of the original wound size) at wound dressing changes on Day 7, Day 10, Day 14, Day 18, Day 21, and Day 28.
Time Frame
up to 4 weeks
Title
Likert Scale Rating of Efficacy
Description
Participants and investigators were asked to grade the efficacy of Oleogel-S10 and non-adhesive wound dressing versus non-adhesive wound dressing only on a 5-point Likert scale (treatment with Oleogel-S10 is much more effective, treatment with Oleogel-S10 is more effective, both treatments have the same efficacy, non-adhesive wound dressing only is more effective, non-adhesive wound dressing only is much more effective).
Time Frame
up to 4 weeks
Title
Cosmetic Outcome at 3 and 12 Months After Surgery, Respectively
Description
Blinded photographic evaluation which wound half resembles more closely the surrounding skin with regard to texture, redness, growth of hair, and pigmentation.
Time Frame
3 months and 12 months
Title
Likert Scale Rating of Tolerability
Description
Participants and investigators were asked to evaluate the tolerability of Oleogel-S10 and non-adhesive wound dressing versus non-adhesive wound dressing only (standard of care) on a 5-point Likert scale (treatment with Oleogel-S10 is much better tolerated, treatment with Oleogel-S10 is better tolerated, both treatments are equally well tolerated, standard of care is better tolerated, standard of care is much better tolerated).
Time Frame
up to 4 weeks
Title
Pharmacokinetic (PK) Data (Number of Plasma Samples With Measurable Betulin Concentration)
Description
Systemic presence/concentration of betulin in blood plasma samples. Plasma samples were collected in weekly intervals and at the end of treatment (when wound closure was achieved or at Day 28). Samples were analysed in a central laboratory with a validated LC-MS/MS method with a lower limit of quantification (LLOQ) of 1 ng/mL.
Time Frame
up to 4 weeks
Title
Pharmacokinetic (PK) Data (Plasma Betulin Concentration)
Description
Systemic presence/concentration of betulin in blood plasma samples - values for the number of samples with measurable values in samples above the lower limit of quantification (LLOQ) of 1 ng/mL
Time Frame
up to 4 weeks
Title
Frequency of Adverse Events
Time Frame
Day 0 (start of treatment) until end of treatment (Day 28 or earlier if full wound closure was achieved earlier).
Title
Severity of Adverse Events
Description
Adverse Events were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) as being mild (NCI CTCAE Grade 1), moderate (NCI CTCAE Grade 2), severe (NCI CTCAE Grade 3), life-threatening (NCI CTCAE Grade 4) or death (NCI CTCAE Grade 5).
Time Frame
Day 0 (start of treatment) until end of treatment (Day 28 or earlier if full wound closure was achieved earlier).
Title
Adverse Events by Relationship to Study Medication
Description
Adverse events were assessed as being 'unlikely', 'possibly' or 'probably' related to study medication, 'not related' to study medication or the relationship to study medication was rated as 'unknown'.
Time Frame
Day 0 (start of treatment) until end of treatment (Day 28 or earlier if full wound closure was achieved earlier).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Presenting a split-thickness skin graft donor site wound with a minimum size of 15 cm2 and with a minimum width of 3 cm.
Patient is able to understand the Informed Consent Form (ICF) provided and is prepared to comply with all study requirements, including the following: Visiting the trial site for wound dressing change and photo documentation every third or fourth day until both wound halves are closed (but no longer than 28 days after surgery).
Willing to perform all necessary wound dressing changes at the trial site. Also the patient needs to agree to return to site for 3 and 12 months follow-up visits.
Women of childbearing potential must apply highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly (e.g., implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices (IUDs), sexual abstinence, or a vasectomized partner)).
Exclusion Criteria:
Diseases or conditions that could, in the opinion of the Investigator, interfere with the assessment of safety or efficacy.
A skin disorder that is chronic or currently active and which the Investigator considers will adversely affect the healing of the acute wounds or involves the areas to be examined in this trial.
A history of clinically significant hypersensitivity to any of the drugs, surgical dressings or excipients to be used in this trial.
Known multiple allergic disorders.
Taking, or have taken, any investigational drugs within 3 months prior to the screening visit.
Pregnant or breast feeding women are not allowed to participate in the study.
Inappropriate to participate in the study, for any reason, in the opinion of the investigator.
Mental incapacity or language barriers precluding adequate understanding the Informed consent form or co-operation or willingness to follow study procedures.
Previous participation in this study.
Employee at the investigational site, relative or spouse of the investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hans Robert Metelmann, Prof
Organizational Affiliation
Universitätsmedizin Greifswald MKG-Chirurgie/Plastische Operationen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of Graz
City
Graz
Country
Austria
Facility Name
Landesklinik für Dermatologie
City
Salzburg
Country
Austria
Facility Name
Medical University Vienna
City
Vienna
Country
Austria
Facility Name
University Multiprofile Hospital for Active Treatment-"Dr. Georgi Stranski" EAD
City
Pleven
Country
Bulgaria
Facility Name
University Multiprofile Hospital for Active Treatment "Saint George"
City
Plovdiv
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment- Ruse
City
Ruse
Country
Bulgaria
Facility Name
University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I.Pirogov"
City
Sofia
Country
Bulgaria
Facility Name
University Multiprofile Hospital for Active Treatment-Varna at MMA-Sofia
City
Varna
Country
Bulgaria
Facility Name
Universtity Hospital Brno
City
Brno
Country
Czechia
Facility Name
University Hospital Olomouc
City
Olomouc
Country
Czechia
Facility Name
Päijät-Hämeen keskussairaala
City
Lahti
Country
Finland
Facility Name
Satakunnan keskussairaala
City
Pori
Country
Finland
Facility Name
Trauma Hospital
City
Berlin
Country
Germany
Facility Name
University Hospital
City
Düsseldorf
Country
Germany
Facility Name
Essen University Hospital
City
Essen
Country
Germany
Facility Name
University Hospital
City
Frankfurt
Country
Germany
Facility Name
University Medical Center
City
Freiburg
Country
Germany
Facility Name
University Medicine Greifswald
City
Greifswald
Country
Germany
Facility Name
HELIOS Clinic
City
Krefeld
Country
Germany
Facility Name
University Medical Center
City
Mainz
Country
Germany
Facility Name
Klinikum rechts der Isar
City
München
Country
Germany
Facility Name
Klinikum Offenbach am Main
City
Offenbach
Country
Germany
Facility Name
Univesity Hospital Gdansk
City
Gdansk
Country
Poland
Facility Name
Samodzelny Publiczny Szpital Kliniczny Nr. 1
City
Lublin
Country
Poland
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
28400148
Citation
Barret JP, Podmelle F, Lipovy B, Rennekampff HO, Schumann H, Schwieger-Briel A, Zahn TR, Metelmann HR; BSH-12 and BSG-12 study groups. Accelerated re-epithelialization of partial-thickness skin wounds by a topical betulin gel: Results of a randomized phase III clinical trials program. Burns. 2017 Sep;43(6):1284-1294. doi: 10.1016/j.burns.2017.03.005. Epub 2017 Apr 8.
Results Reference
result
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Oleogel-S10 in Wound Healing of Split-Thickness Skin Graft Donor Sites (BSH-12)
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