EPIGRAAFT: Epidermal Grafting in Wound Healing

• Sponsor: University College, London (Other)
• Overall Status: Completed
• CT.gov ID: NCT02535481
• Collaborator: (none)
• Enrollment: 44
• Location: 1
• Arms: 2
• Actual Duration (Months): 25
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

Split thickness skin grafting is the normal standard of care for wound closure. However, this is an invasive procedure and associated with pain also there can be additional donor site morbidity. Epidermal grafting is an emerging clinical alternative that is gaining clinical practise. Epidermal grafting (EG) is an alternative method of autologous skin grafting that 'harvests' a finer layer of skin than traditional Split thickness skin grafting (SSG). This potentially results in less pain and reduced donor site morbidity but only delivers several cell layers to the wound so may be less effective at healing a wound. It is not known if EG is an effective alternative to SSG.

Further the mechanism to achieve wound healing may be different. EG promotes wound healing by expressing growth factors that accelerates wound healing and encourages keratinocyte migration. Whereas SSG is a transplant of several skin layers that integrated to the existing wound bed as a formal skin covering.

The investigators wish to compare these two clinical practises; epidermal grafting and split thickness skin grafting in wound healing. Further to undertake a translational study to investigate the mechanism by which each technique achieves wound healing.

Condition or Disease	Intervention/Treatment	Phase
Ulcer; Skin Ulcer; Wounds and Injuries	Device: Epidermal grafting; Procedure: Split thickness skin grafting	N/A

Detailed Description

This study evaluates the efficacy of EG, as an alternative to current wound management therapy, SSG. In a pilot study carried out in our centre (unpublished data), the investigators noted that this technique offers a method of autologous skin harvesting with minimal or no pain and a scar free donor site. Moreover, complete wound epithelialisation was achieved while maintaining patient independence. Therefore, this device has the potential to save healthcare resources, by eliminating the need for theatre space and a hospital bed, and result in better Patient Reported Outcomes Measures.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-centre Randomised Controlled Trial to Compare Epidermal Grafting With Split Skin Grafting for Wound Healing
• Actual Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Aug 1, 2017
• Actual Study Completion Date: Nov 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Epidermal Graft The Cellutome Epidermal Graft Harvesting System will be used to harvest epidermal grafts as per existing normal clinical practice.	Device: Epidermal grafting; The Cellutome Epidermal Graft Harvesting System will be used to harvest epidermal grafts.; Other Names: CelluTome
Experimental: Split Thickness Skin Graft Split thickness skin graft will be harvested using air dermatome as per normal clinical practise.	Procedure: Split thickness skin grafting; Split thickness skin grafting will be performed as per normal clinical practice.

Outcome Measures

Primary Outcome Measures

1. Number of Wounds With Complete Healing [6 weeks and 3 months]

   Number of wounds with complete healing at 6 weeks

2. Mean Time for Donor Site Healing [3 months]

   Complete donor site healing was defined as 100% re-epithelialisation and not requiring further dressings

Secondary Outcome Measures

1. Time for Wound Healing [3 months]

   Complete wound healing was defined as 100% re-epithelialisation and not requiring further dressings

2. Donor Site Morbidity [6 weeks and 3 months]

   The donor site morbidity was measured using the Vancouver Scar Scale (VSS). Total score scale ranges from 0 to 13. Lower score is more desirable as it represents a scar resembling normal surrounding skin. The scale assesses 4 categories: vascularity, height, pliability, and pigmentation. Total score is obtained by the sum of the categories.

3. Patient Reported Outcome Measure (PROM) [6 weeks and 3 months]

   Patient reported outcome measure was assessed using a validated skin graft satisfaction questionnaire.The skin graft satisfaction questionnaire has a scale ranging from 1 to 7, with 1 representing very unsatisfied while 7 represents very satisfied. Hence, higher score represent higher satisfaction.

4. Adverse Events [3 months]

   Number of participants with of adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Male or female

2. Age 18-90

3. Wound measuring more than 1cm x 1cm and lesser than 5cm x 5cm (1% TBSA)

4. Wound with clean, healthy granulating bed, with minimal adherent slough

5. Patient understands and is willing to participate and can comply with weekly visits and follow-up regime

Exclusion Criteria:

1. Wound with active infection

2. Wound at plantar of the foot

3. Patients unsuitable for Split Skin Grafting

4. Previous history of excessive bleeding associated with surgical biopsies or trauma

5. Allergies to tegaderm (and other dressings used in the study)

6. Known uncontrolled Diabetes Mellitus, as measured by an HbA1c > 10%.

7. Presence of one or more medical conditions, including renal, hepatic, hematologic, active auto-immune or immune diseases that, would make the subject an inappropriate candidate for this ulcer healing study

8. Patient not fit for surgery (ASA classification > 4)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Free Hampstead NHS Trust Hospital	London		United Kingdom	NW3 2QG

Sponsors and Collaborators

• University College, London

Investigators

• Principal Investigator: Toby Richards, MD FRCS, University College, London
• Principal Investigator: Afshin Mosahebi, MBBS FRCS PhD MBA, Royal Free Hospital NHS Foundation Trust

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 18, 2016

More Information

Publications

None provided.

• Responsible Party: University College, London
• ClinicalTrials.gov Identifier: NCT02535481
• Other Study ID Numbers: 15/0079
• First Posted: Aug 28, 2015
• Last Update Posted: Aug 10, 2020
• Last Verified: Jul 1, 2020

• Keywords provided by University College, London: epidermal graft; suction blister; blister graft; suction graft; Epidermis/su, tr [Surgery, Transplantation]
• Additional relevant MeSH terms: Skin Ulcer; Ulcer; Wounds and Injuries

Study Results

Participant Flow

Recruitment Details	A total of 61 patients were screened for eligibility; 44 of them fulfilled the inclusion criteria and were randomized to the two study groups (EG and SSG) between October 2015 and September 2017. Participants were recruited at the Royal Free London NHS Foundation Trust Hospital.

Arm/Group Title	Epidermal Graft	Split Thickness Skin Graft
Arm/Group Description	Epidermal grafting: The Cellutome Epidermal Graft Harvesting System was used to harvest epidermal grafts.	Split thickness skin grafting: Split thickness skin grafting was performed as per normal clinical practice.
Period Title: Overall Study
STARTED	22	22
COMPLETED	22	22
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Epidermal Graft	Split Thickness Skin Graft	Total
Arm/Group Description	Epidermal grafting: The Cellutome Epidermal Graft Harvesting System was used to harvest epidermal grafts.	Split thickness skin grafting: Split thickness skin grafting was performed as per normal clinical practice.	Total of all reporting groups
Overall Participants	22	22	44
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.1 (19.9)	59 (18)	58.7 (19)
Sex: Female, Male (Count of Participants)
Female	9 40.9%	5 22.7%	14 31.8%
Male	13 59.1%	17 77.3%	30 68.2%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Wound size (cm^2) (cm^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm^2]	12.7 (9.9)	16.5 (11)	14.6 (10.7)
Duration of wound (week) (week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [week]	48.9 (75.4)	7.86 (16.1)	28.4 (58.3)

Outcome Measures

1. Primary Outcome

Title	Number of Wounds With Complete Healing
Description	Number of wounds with complete healing at 6 weeks
Time Frame	6 weeks and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epidermal Graft	Split Thickness Skin Graft
Arm/Group Description	Epidermal grafting: The Cellutome Epidermal Graft Harvesting System was used to harvest epidermal grafts.	Split thickness skin grafting: Split thickness skin grafting was performed as per normal clinical practice.
Measure Participants	22	22
Measure Number of wounds	22	22
6 weeks	9	13
3 months	16	20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Epidermal Graft, Split Thickness Skin Graft
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.366
	Comments	At 6 weeks
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Epidermal Graft, Split Thickness Skin Graft
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments	At 3 months
	Method	Fisher Exact
	Comments

2. Primary Outcome

Title	Mean Time for Donor Site Healing
Description	Complete donor site healing was defined as 100% re-epithelialisation and not requiring further dressings
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epidermal Graft	Split Thickness Skin Graft
Arm/Group Description	Epidermal grafting: The Cellutome Epidermal Graft Harvesting System was used to harvest epidermal grafts.	Split thickness skin grafting: Split thickness skin grafting was performed as per normal clinical practice.
Measure Participants	22	22
Mean (95% Confidence Interval) [days]	4.86	21.32

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Epidermal Graft, Split Thickness Skin Graft
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments	Kaplan-Meier analysis of cumulative wound healing followed by a log rank test

3. Secondary Outcome

Title	Time for Wound Healing
Description	Complete wound healing was defined as 100% re-epithelialisation and not requiring further dressings
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epidermal Graft	Split Thickness Skin Graft
Arm/Group Description	Epidermal grafting: The Cellutome Epidermal Graft Harvesting System was used to harvest epidermal grafts.	Split thickness skin grafting: Split thickness skin grafting was performed as per normal clinical practice.
Measure Participants	22	22
Mean (95% Confidence Interval) [week]	7.81	6.59

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Epidermal Graft, Split Thickness Skin Graft
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Log Rank
	Comments

4. Secondary Outcome

Title	Donor Site Morbidity
Description	The donor site morbidity was measured using the Vancouver Scar Scale (VSS). Total score scale ranges from 0 to 13. Lower score is more desirable as it represents a scar resembling normal surrounding skin. The scale assesses 4 categories: vascularity, height, pliability, and pigmentation. Total score is obtained by the sum of the categories.
Time Frame	6 weeks and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epidermal Graft	Split Thickness Skin Graft
Arm/Group Description	Epidermal grafting: The Cellutome Epidermal Graft Harvesting System was used to harvest epidermal grafts.	Split thickness skin grafting: Split thickness skin grafting was performed as per normal clinical practice.
Measure Participants	22	22
6 weeks	0.14 (0.45)	3.73 (0.69)
3 months	0.09 (0.29)	2.91 (0.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Epidermal Graft, Split Thickness Skin Graft
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Patient Reported Outcome Measure (PROM)
Description	Patient reported outcome measure was assessed using a validated skin graft satisfaction questionnaire.The skin graft satisfaction questionnaire has a scale ranging from 1 to 7, with 1 representing very unsatisfied while 7 represents very satisfied. Hence, higher score represent higher satisfaction.
Time Frame	6 weeks and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epidermal Graft	Split Thickness Skin Graft
Arm/Group Description	Epidermal grafting: The Cellutome Epidermal Graft Harvesting System was used to harvest epidermal grafts.	Split thickness skin grafting: Split thickness skin grafting was performed as per normal clinical practice.
Measure Participants	22	22
6 weeks	7	6
3 months	7	6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Epidermal Graft, Split Thickness Skin Graft
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	At 6 weeks
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Epidermal Graft, Split Thickness Skin Graft
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	At 3 months
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

Title	Adverse Events
Description	Number of participants with of adverse events
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epidermal Graft	Split Thickness Skin Graft
Arm/Group Description	Epidermal grafting: The Cellutome Epidermal Graft Harvesting System was used to harvest epidermal grafts.	Split thickness skin grafting: Split thickness skin grafting was performed as per normal clinical practice.
Measure Participants	22	22
Number [participants]	0 0%	0 0%

Adverse Events

Time Frame	3 months
Adverse Event Reporting Description	The incidence of serious adverse events (SAEs) include mortality of any cause within the three months duration from the time of initial therapy, and the incidence of device-related adverse events (DAEs) and wound-related adverse events (WAEs) occurring within the study duration.
Arm/Group Title	Epidermal Graft		Split Thickness Skin Graft
Arm/Group Description	Epidermal grafting: The Cellutome Epidermal Graft Harvesting System was used to harvest epidermal grafts.		Split thickness skin grafting: Split thickness skin grafting was performed as per normal clinical practice.
All Cause Mortality
	Epidermal Graft		Split Thickness Skin Graft
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)
Serious Adverse Events
	Epidermal Graft		Split Thickness Skin Graft
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Epidermal Graft		Split Thickness Skin Graft
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.