Oleogel-S10 Versus Standard of Care in Healing of Grade 2a Burn Wounds

• Sponsor: Birken AG (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01657292
• Collaborator: (none)
• Enrollment: 61
• Locations: 9
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The main goal of this phase III clinical trial is to show safety and efficacy of Oleogel-S10 in the acceleration of wound healing of grade 2a burn wounds.

Condition or Disease	Intervention/Treatment	Phase
Burns	Drug: Oleogel-S10 ointment; Device: Octenilin® wound gel	Phase 3

Detailed Description

Oleogel-S10 has shown efficacy and was well tolerated in previous clinical trials in patients with skin lesions. Especially the results in the split-thickness skin graft donor site, which is regarded as an excellent model for any kind of superficial wounds in human skin, suggest that Oleogel-S10 should be efficacious and safe in treatment of grade 2a burns.

The present Phase III clinical trial in grade 2a burns is initiated in order to measure the wound healing progress applying objective methods, i.e., the time to healing and the grade of epithelialization of the wound.

In this study, grade 2a burn wounds are separated into two halves: Following wound cleaning and disinfection, wounds are separated into two wound halves. Randomly assigned, one wound half receives Oleogel-S10 ointment, the other wound half standard of care treatment.

Wound healing progress is documented by photos which are assessed by expert reviewers blinded to the treatment of the wound halves.

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Healing of Grade 2a Partial-Thickness Burn Wounds
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oleogel-S10 ointment Intra-individual comparison. Oleogel-S10 ointment is administered to one randomly assigned wound half.	Drug: Oleogel-S10 ointment; Intraindividual comparison: One randomly assigned wound half is treated with Oleogel-S10 ointment and fatty gauze wound dressing; Device: Octenilin® wound gel; Intraindividual comparison: The other wound half is treated with Octenilin® wound gel and fatty gauze wound dressing; Other Names: Contains Octenidine
Other: Octenilin® wound gel Intraindividual comparison: The other wound half receives disinfectant Octenilin® wound gel.	Drug: Oleogel-S10 ointment; Intraindividual comparison: One randomly assigned wound half is treated with Oleogel-S10 ointment and fatty gauze wound dressing; Device: Octenilin® wound gel; Intraindividual comparison: The other wound half is treated with Octenilin® wound gel and fatty gauze wound dressing; Other Names: Contains Octenidine

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With Earlier Healing of the Wound Half Treated With Oleogel-S10 Compared to the Wound Half Receiving Standard of Care [2 to 3 weeks]

   Photo-based evaluation by independent experts blinded to the treatment regime.

Secondary Outcome Measures

1. Intra-individual Difference in Time to Wound Closure Between Wound Halves, Either Treated With Oleogel-S10 or Treated With Standard of Care [2 to 3 weeks]

2. Time From Study Start After Burn Accident Until Wound Closure is Achieved Separately for Wound Halves Treated With Oleogel-S10 vs. Standard of Care [2 to 3 weeks]

3. Percentage of Patients With Wound Closure at Different Time Points [2 to 3 weeks]

4. Percentage of Wound Epithelialization at Different Time Points as Assessed by the Investigator [2 to 3 weeks]

5. Likert Scale Rating of Efficacy (Evaluated by Both the Investigators and Patients) [2 to 3 weeks]

   By direct comparison of the separate simultaneous treatments for the two wound halves, patients and investigators, respectively, are asked to grade the efficacy of Oleogel-S10 Versus Standard of Care on a questionnaire with a 5-point graded visual analogue scale

6. Cosmetic Outcome After 3 and 12 Months After Burn Accident, in Relation to Texture, Redness, Growth of Hair and Pigmentation, Based on Blinded Photo Evaluation [3 and 12 months]

7. Likert Scale Rating of Tolerance (Evaluated by Both the Investigators and Patients) [2 to 3 weeks]

   By direct comparison of the separate simultaneous treatments for the two wound halves, patients and investigators, respectively, are asked to provide their opinion on the tolerance of Oleogel-S10 Versus Standard of Care on a questionnaire with a 5-point graded visual analogue scale

8. PK Data: Systemic Presence/Concentration of Betulin in Blood Plasma Samples [2 to 3 weeks]

9. Microbial Colonization of the Wound Halves [2 to 3 weeks]

10. Assessment of Adverse Events [2 to 3 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients at least 18 years old who have provided written informed consent.

• Presenting with acute grade 2a burn wounds (as graded by an expert surgeon assisted by LDI or a multispectral imaging system) within 48 hours after injury.

• Burn wound caused by fire burn, heat burn or scalding.

• Burn patients with grade 2a burn wounds between 80 cm2 and less than 25% of their TBSA (alternatively, 2 comparable wounds with size more than 40 cm2 each and less than 12.5% of the TBSA each are allowed).

• Patient is able to understand the Informed Consent Form provided and is prepared to comply with all study requirements, including the following: Visiting the trial site for wound dressing changes at least every second day (if patient is not hospitalized) and photo documentation until full wound closure or until the Investigator decides to change medication and/or treatment after day 21 after start of treatment

• 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:

• Suffering from chemical burns, or electrical burns or sunburns

• Having already received treatment for their burn with silver sulfadiazine (obscures photographic wound evaluation).

• Positive blood culture after the burn.

• Diseases or conditions that could, in the opinion of the Investigator, interfere with the assessment of safety, tolerance 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 or surgical dressings 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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Unfallkrankenhaus Berlin	Berlin		Germany
2	Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil	Bochum		Germany
3	Universitätsklinikum Schleswig-Holstein	Lübeck		Germany
4	Linköping University Hospital	Linköping		Sweden
5	University Hospital	Uppsala		Sweden
6	Centre Hospitalier Universitaire Vaudois	Lausanne		Switzerland
7	University Hospitals Birmingham NHS Foundation Trust	Birmingham		United Kingdom
8	Broomfield Hospital	Chelmsford		United Kingdom
9	Queen Victoria Hospital	East Grinstead		United Kingdom

Sponsors and Collaborators

• Birken AG

Investigators

• Principal Investigator: Bernd Hartmann, Dr., Trauma Hospital Berlin, Warener Str. 7, 12683 Berlin, Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Birken AG
• ClinicalTrials.gov Identifier: NCT01657292
• Other Study ID Numbers: BBW-11; 2012-000362-38
• First Posted: Aug 6, 2012
• Last Update Posted: Sep 28, 2015
• Last Verified: Aug 1, 2015

• Keywords provided by Birken AG: Wound healing; Burn wound; Superficial partial-thickness burn wound; Grade 2a burn wounds; Time to wound closure
• Additional relevant MeSH terms: Burns; Octenidine

Study Results

Participant Flow

Recruitment Details	Study participants were enrolled from 31-Aug-2012 to 10-Jul-2013, in 10 clinical centres in 4 countries: Germany (4 centers), Uk (3 centers), Sweden (2 centers), and Switzerland (1 center).
Pre-assignment Detail	66 patients were screened of which 5 violated eligibility criteria and thus 61 subjects were treated.

Arm/Group Title	Entire Study Population
Arm/Group Description	All patients treated with Oleogel-S10 and Octenilin® wound gel.
Period Title: Overall Study
STARTED	61
COMPLETED	51
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	All patients treated with Oleogel-S10 and Octenilin® wound gel.
Overall Participants	61
Age (Count of Participants)
<=18 years	1 1.6%
Between 18 and 65 years	54 88.5%
>=65 years	6 9.8%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	41
Sex: Female, Male (Count of Participants)
Female	19 31.1%
Male	42 68.9%
Region of Enrollment (participants) [Number]
Sweden	3 4.9%
United Kingdom	28 45.9%
Switzerland	4 6.6%
Germany	26 42.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Earlier Healing of the Wound Half Treated With Oleogel-S10 Compared to the Wound Half Receiving Standard of Care
Description	Photo-based evaluation by independent experts blinded to the treatment regime.
Time Frame	2 to 3 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all patients who were treated at least once with Oleogel-S10 or Octenilin® wound gel (as randomised) and for whom a difference in wound healing between the treatment was observed.

Arm/Group Title	Entire Study Population
Arm/Group Description	All patients treated with Oleogel-S10 and Octenilin® wound gel.
Measure Participants	35
Number (95% Confidence Interval) [percentage of patients]	85.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Entire Study Population
	Comments	All patients received both treatments and treatments were intra-individually compared. Hypotheses tested: H0: s0 ≤0.5 and H1: s0 >0.5 (with s0=rate of superiority of Oleogel-S10).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	1-sided, significance level = 0.025
	Method	Binomial test
	Comments

2. Secondary Outcome

Title	Intra-individual Difference in Time to Wound Closure Between Wound Halves, Either Treated With Oleogel-S10 or Treated With Standard of Care
Time Frame	2 to 3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Time From Study Start After Burn Accident Until Wound Closure is Achieved Separately for Wound Halves Treated With Oleogel-S10 vs. Standard of Care
Time Frame	2 to 3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Percentage of Patients With Wound Closure at Different Time Points
Time Frame	2 to 3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Percentage of Wound Epithelialization at Different Time Points as Assessed by the Investigator
Time Frame	2 to 3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Likert Scale Rating of Efficacy (Evaluated by Both the Investigators and Patients)
Description	By direct comparison of the separate simultaneous treatments for the two wound halves, patients and investigators, respectively, are asked to grade the efficacy of Oleogel-S10 Versus Standard of Care on a questionnaire with a 5-point graded visual analogue scale
Time Frame	2 to 3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Cosmetic Outcome After 3 and 12 Months After Burn Accident, in Relation to Texture, Redness, Growth of Hair and Pigmentation, Based on Blinded Photo Evaluation
Time Frame	3 and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Likert Scale Rating of Tolerance (Evaluated by Both the Investigators and Patients)
Description	By direct comparison of the separate simultaneous treatments for the two wound halves, patients and investigators, respectively, are asked to provide their opinion on the tolerance of Oleogel-S10 Versus Standard of Care on a questionnaire with a 5-point graded visual analogue scale
Time Frame	2 to 3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	PK Data: Systemic Presence/Concentration of Betulin in Blood Plasma Samples
Time Frame	2 to 3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Microbial Colonization of the Wound Halves
Time Frame	2 to 3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Assessment of Adverse Events
Time Frame	2 to 3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Day 0 (start of treatment) till end of treatment (Day 21 or earlier if full wound closure was achieved earlier, or later, if the investigator decided to change medication and/or treatment due to unsatisfying wound closure after Day 21).
Arm/Group Title	Entire Study Population - Systemic AEs		Oleogel-S10 Localized AE		Octenilin Localized AE		Localized AE Both Wound Halves
Arm/Group Description	All patients treated with Oleogel-S10 and Octenilin® wound gel. Systemic AEs which are not localized to the wound application site are reported under this arm.		All patients treated with Oleogel-S10 and Octenilin® wound gel. Application site reactions which occurred only at the Oleogel-S10 wound half are reported under this arm.		All patients treated with Oleogel-S10 and Octenilin® wound gel. Application site reactions which occurred only at the Octenilin® wound half are reported under this arm.		All patients treated with Oleogel-S10 and Octenilin® wound gel. Application site reactions which occurred at both the Octenilin® wound half and Oleogel-S10 wound half in one patient are reported under this arm.
All Cause Mortality
	Entire Study Population - Systemic AEs		Oleogel-S10 Localized AE		Octenilin Localized AE		Localized AE Both Wound Halves
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Entire Study Population - Systemic AEs		Oleogel-S10 Localized AE		Octenilin Localized AE		Localized AE Both Wound Halves
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/61 (3.3%)		1/61 (1.6%)		1/61 (1.6%)		4/61 (6.6%)
General disorders
Condition aggravated	0/61 (0%)		0/61 (0%)		0/61 (0%)		2/61 (3.3%)
Pyrexia	1/61 (1.6%)		0/61 (0%)		0/61 (0%)		0/61 (0%)
Infections and infestations
Soft tissue infection	0/61 (0%)		0/61 (0%)		1/61 (1.6%)		0/61 (0%)
Wound infection	0/61 (0%)		0/61 (0%)		0/61 (0%)		2/61 (3.3%)
Injury, poisoning and procedural complications
Wound necrosis	0/61 (0%)		1/61 (1.6%)		0/61 (0%)		0/61 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tonsil cancer	1/61 (1.6%)		0/61 (0%)		0/61 (0%)		0/61 (0%)
Other (Not Including Serious) Adverse Events
	Entire Study Population - Systemic AEs		Oleogel-S10 Localized AE		Octenilin Localized AE		Localized AE Both Wound Halves
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/61 (0%)		0/61 (0%)		0/61 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Publication requires approval of the sponsor without specification of an embargo time period.