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Oleogel-S10 in Wound Healing of Split-Thickness Skin Graft Donor Sites (BSG-12) (BSG-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
Birken AG
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Participants at least 18 years old who have provided written informed consent
  • Presenting a split-thickness skin graft donor site wound with a minimum size of 15 cm2 and with a minimum width of 3 cm.
  • Participant was able to understand the Informed Consent Form (ICF) provided and was 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 were closed (but no longer than 28 days after surgery).
  • Willing to perform all necessary wound dressing changes at the trial site. Also the participant needed to agree to return to site for 3 and 12 months follow-up visits.
  • Women of childbearing potential who were in the period between menarche and menopause needed to apply a 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). Birth control method needed to have been applied for at least 1 monthly cycle prior to first administration of study drug, be maintained during the study treatment phase and continued for at least 30 days after the last administration of study drug. Sexually active, non-vasectomized men needed to use a barrier method (condoms) during the treatment phase of this clinical trial.

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 was chronic or currently active and which the Investigator considered would adversely affect the healing of the acute wounds or involved 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 were 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 ICF 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

  • CHU de Bordeaux
  • Hôpital de la Conception
  • CHU de Nantes
  • KAT General Hospital of Attica
  • National University, "Andreas Syggros" Skin & Venereal Diseases Hospital
  • Aristotle University General Hospital
  • Riga East University Hospital, Microsurgery Center
  • Riga East University Hospital, State Burn Center
  • Hospital de la Santa Creu i Sant Pau
  • Hospital Universitari Vall d'Hebron
  • Hospital Universitario de Getafe
  • Hopital Universitari i Politecnic La Fe
  • Hospital Universitario Rio Ortega
  • Hospital Miguel Servet

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.

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 110 participants with missing values replaced by a value of 0, for outcome measure 2 missing values were not replaced. For 2 of the 110 wounds data were missing, thus the reported values are calculated from 108 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, non-adhesive wound dressing only is better tolerated, non-adhesive wound dressing only 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

First Posted
March 5, 2013
Last Updated
July 17, 2018
Sponsor
Birken AG
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1. Study Identification

Unique Protocol Identification Number
NCT01807650
Brief Title
Oleogel-S10 in Wound Healing of Split-Thickness Skin Graft Donor Sites (BSG-12)
Acronym
BSG-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
July 2018
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
September 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 show safety and efficacy of Oleogel-S10 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 blinded 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
112 (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.
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
2 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 110 participants with missing values replaced by a value of 0, for outcome measure 2 missing values were not replaced. For 2 of the 110 wounds data were missing, thus the reported values are calculated from 108 STSG donor site wound halves by intervention (Oleogel-S10 and non-adhesive wound dressing vs. non-adhesive wound dressing only).
Time Frame
2 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
2 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
2 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
2 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
2 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, non-adhesive wound dressing only is better tolerated, non-adhesive wound dressing only is much better tolerated).
Time Frame
2 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: Participants at least 18 years old who have provided written informed consent Presenting a split-thickness skin graft donor site wound with a minimum size of 15 cm2 and with a minimum width of 3 cm. Participant was able to understand the Informed Consent Form (ICF) provided and was 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 were closed (but no longer than 28 days after surgery). Willing to perform all necessary wound dressing changes at the trial site. Also the participant needed to agree to return to site for 3 and 12 months follow-up visits. Women of childbearing potential who were in the period between menarche and menopause needed to apply a 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). Birth control method needed to have been applied for at least 1 monthly cycle prior to first administration of study drug, be maintained during the study treatment phase and continued for at least 30 days after the last administration of study drug. Sexually active, non-vasectomized men needed to use a barrier method (condoms) during the treatment phase of this clinical trial. 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 was chronic or currently active and which the Investigator considered would adversely affect the healing of the acute wounds or involved 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 were 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 ICF 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
Juan Pedro Barret Nerin, MD
Organizational Affiliation
Hospital Universitari Vall d´Hebron, Barcelona, Spain
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Bordeaux
City
Bordeaux
Country
France
Facility Name
Hôpital de la Conception
City
Marseille
Country
France
Facility Name
CHU de Nantes
City
Nantes
Country
France
Facility Name
KAT General Hospital of Attica
City
Athens
Country
Greece
Facility Name
National University, "Andreas Syggros" Skin & Venereal Diseases Hospital
City
Athens
Country
Greece
Facility Name
Aristotle University General Hospital
City
Thessaloniki
Country
Greece
Facility Name
Riga East University Hospital, Microsurgery Center
City
Riga
Country
Latvia
Facility Name
Riga East University Hospital, State Burn Center
City
Riga
Country
Latvia
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario de Getafe
City
Madrid
Country
Spain
Facility Name
Hopital Universitari i Politecnic La Fe
City
Valencia
Country
Spain
Facility Name
Hospital Universitario Rio Ortega
City
Valladolid
Country
Spain
Facility Name
Hospital Miguel Servet
City
Zaragoza
Country
Spain

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
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Oleogel-S10 in Wound Healing of Split-Thickness Skin Graft Donor Sites (BSG-12)

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