Effect of Platelet Rich Plasma and Keratinocyte Suspensions on Wound Healing

• Sponsor: Centre Hospitalier Universitaire Vaudois (Other)
• Overall Status: Completed
• CT.gov ID: NCT00856934
• Collaborator: (none)
• Enrollment: 45
• Location: 1
• Arms: 3

Study Details

Study Description

Brief Summary

This prospective randomized trial evaluated the impact of autologous keratinocytes suspended in platelet concentrates on healing skin graft donor site wounds. It was hypothesized that the treatment would speed and improve wound healing.

Condition or Disease	Intervention/Treatment	Phase
Skin Graft	Biological: Autologous Platelet Rich Plasma; Biological: Keratinocyte suspension; Other: Standard dressings	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A New Model to Enhance Wound Healing Using Autologous Keratinocytes in Platelet Concentrates - a Prospective Randomized Trial.
• Study Start Date: Jun 1, 2005
• Actual Primary Completion Date: Mar 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Control Wounds covered with standard dressings: three layers of paraffin gauze, standard bandages, elastic bandage.	Other: Standard dressings; Three layers of paraffin gauze, topped with standard dry bandages and an elastic bandage.
Experimental: PRP PRP sprayed onto the wound bed with Calcium Choride. Wounds covered with same standard dressings used in control group.	Biological: Autologous Platelet Rich Plasma; Platelet Rich Plasma isolated from patient blood sprayed onto wound bed along with 10% Calcium Chloride solution in a 10 to 1 proportion.; Other: Standard dressings; Three layers of paraffin gauze, topped with standard dry bandages and an elastic bandage.
Experimental: PRP+K Keratinocytes suspended in PRP sprayed onto the wound bed with Calcium Choride. Wounds covered with same standard dressings used in control group.	Biological: Autologous Platelet Rich Plasma; Platelet Rich Plasma isolated from patient blood sprayed onto wound bed along with 10% Calcium Chloride solution in a 10 to 1 proportion.; Biological: Keratinocyte suspension; Autologous keratinocytes isolated from skin biopsy suspended in platelet rich plasma before spraying.; Other: Standard dressings; Three layers of paraffin gauze, topped with standard dry bandages and an elastic bandage.

Outcome Measures

Primary Outcome Measures

1. Complete Wound Healing [Post operative day 5 and every other day thereafter]

   Time required for complete epithelialization in days

Secondary Outcome Measures

1. Pain [Post operative day 5]

   Pain evaluated on a Visual Analog Scale (VAS) from 0 (no pain) to 10 (extreme pain), specifically during dressing replacement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Skin graft donor sites total surface < 15% BSA

• Skin graft donor site size: 0.2mm deep, 30 to 40 cm2 surface area

Exclusion Criteria:

• Patients treated with immunosuppressors

• Patients treated with corticoids

• Patients suffering from terminal renal insufficiency

• Patients suffering from severe peripheral arteriopathy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre hospitalier Universitaire Vaudois	Lausanne	Vaud	Switzerland	1011

Sponsors and Collaborators

• Centre Hospitalier Universitaire Vaudois

Investigators

• Principal Investigator: Wassim Raffoul, PD, MER, CHUV - CPR

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ansel JC, Tiesman JP, Olerud JE, Krueger JG, Krane JF, Tara DC, Shipley GD, Gilbertson D, Usui ML, Hart CE. Human keratinocytes are a major source of cutaneous platelet-derived growth factor. J Clin Invest. 1993 Aug;92(2):671-8.
• Atiyeh BS, Gunn SW, Hayek SN. State of the art in burn treatment. World J Surg. 2005 Feb;29(2):131-48. Review.
• Ballaun C, Weninger W, Uthman A, Weich H, Tschachler E. Human keratinocytes express the three major splice forms of vascular endothelial growth factor. J Invest Dermatol. 1995 Jan;104(1):7-10.
• Brissett AE, Hom DB. The effects of tissue sealants, platelet gels, and growth factors on wound healing. Curr Opin Otolaryngol Head Neck Surg. 2003 Aug;11(4):245-50. Review.
• Brown LF, Yeo KT, Berse B, Yeo TK, Senger DR, Dvorak HF, van de Water L. Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med. 1992 Nov 1;176(5):1375-9.
• Carter CA, Jolly DG, Worden CE Sr, Hendren DG, Kane CJ. Platelet-rich plasma gel promotes differentiation and regeneration during equine wound healing. Exp Mol Pathol. 2003 Jun;74(3):244-55.
• Decline F, Rousselle P. Keratinocyte migration requires alpha2beta1 integrin-mediated interaction with the laminin 5 gamma2 chain. J Cell Sci. 2001 Feb;114(Pt 4):811-23.
• Di Giulio AM, Picotti GB, Cesura AM, Panerai AE, Mantegazza P. Met-enkephalin immunoreactivity in blood platelets. Life Sci. 1982 May 10;30(19):1605-14.
• Eaglstein WH, Falanga V. Chronic wounds. Surg Clin North Am. 1997 Jun;77(3):689-700. Review.
• Edwards R, Harding KG. Bacteria and wound healing. Curr Opin Infect Dis. 2004 Apr;17(2):91-6. Review.
• Feldman DL. Which dressing for split-thickness skin graft donor sites? Ann Plast Surg. 1991 Sep;27(3):288-91. Review.
• Feliciani C, Gupta AK, Sauder DN. Keratinocytes and cytokine/growth factors. Crit Rev Oral Biol Med. 1996;7(4):300-18. Review.
• Fu X, Li X, Cheng B, Chen W, Sheng Z. Engineered growth factors and cutaneous wound healing: success and possible questions in the past 10 years. Wound Repair Regen. 2005 Mar-Apr;13(2):122-30. Review.
• Gharaee-Kermani M, Phan SH. Role of cytokines and cytokine therapy in wound healing and fibrotic diseases. Curr Pharm Des. 2001 Jul;7(11):1083-103. Review.
• Hierner R, Degreef H, Vranckx JJ, Garmyn M, Massagé P, van Brussel M. Skin grafting and wound healing-the "dermato-plastic team approach". Clin Dermatol. 2005 Jul-Aug;23(4):343-52. Review.
• Knighton DR, Ciresi KF, Fiegel VD, Austin LL, Butler EL. Classification and treatment of chronic nonhealing wounds. Successful treatment with autologous platelet-derived wound healing factors (PDWHF). Ann Surg. 1986 Sep;204(3):322-30.
• Mazzucco L, Medici D, Serra M, Panizza R, Rivara G, Orecchia S, Libener R, Cattana E, Levis A, Betta PG, Borzini P. The use of autologous platelet gel to treat difficult-to-heal wounds: a pilot study. Transfusion. 2004 Jul;44(7):1013-8.
• McKay IA, Leigh IM. Epidermal cytokines and their roles in cutaneous wound healing. Br J Dermatol. 1991 Jun;124(6):513-8. Review.
• Robson MC, Stenberg BD, Heggers JP. Wound healing alterations caused by infection. Clin Plast Surg. 1990 Jul;17(3):485-92. Review.
• Smith DJ Jr, Thomson PD, Garner WL, Rodriguez JL. Donor site repair. Am J Surg. 1994 Jan;167(1A):49S-51S. Review.
• Tamariz-Domínguez E, Castro-Muñozledo F, Kuri-Harcuch W. Growth factors and extracellular matrix proteins during wound healing promoted with frozen cultured sheets of human epidermal keratinocytes. Cell Tissue Res. 2002 Jan;307(1):79-89. Epub 2001 Nov 14.
• Valbonesi M, Giannini G, Migliori F, Dalla Costa R, Galli A. The role of autologous fibrin-platelet glue in plastic surgery: a preliminary report. Int J Artif Organs. 2002 Apr;25(4):334-8.
• Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev. 2003 Jul;83(3):835-70. Review.

• ClinicalTrials.gov Identifier: NCT00856934
• Other Study ID Numbers: 132/03
• First Posted: Mar 6, 2009
• Last Update Posted: Mar 6, 2009
• Last Verified: Feb 1, 2009

• Keywords provided by , ,: Skin graft donor site healing; skin; wound; platelet concentrate; keratinocytes; burns

Study Results

Participant Flow

Arm/Group Title	Control	PRP	PRP+K
Arm/Group Description	Wounds covered with standard dressings: three layers of paraffin gauze, standard bandages, elastic bandage.	Platelet Rich Plasma (PRP) sprayed onto the wound bed with Calcium Chloride. Wounds covered with same standard dressings used in control group.	Keratinocytes suspended in Platelet Rich Plasma (PRP) sprayed onto the wound bed with Calcium Chloride. Wounds covered with same standard dressings used in control group.
Period Title: Overall Study
STARTED	15	15	15
COMPLETED	15	15	15
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Control	PRP	PRP+K	Total
Arm/Group Description	Wounds covered with standard dressings: three layers of paraffin gauze, standard bandages, elastic bandage.	Platelet Rich Plasma (PRP) sprayed onto the wound bed with Calcium Chloride. Wounds covered with same standard dressings used in control group.	Keratinocytes suspended in Platelet Rich Plasma (PRP) sprayed onto the wound bed with Calcium Chloride. Wounds covered with same standard dressings used in control group.	Total of all reporting groups
Overall Participants	15	15	15	45
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	14 93.3%	12 80%	41 91.1%
>=65 years	0 0%	1 6.7%	3 20%	4 8.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.5 (11.9)	45.5 (15.3)	46.9 (20.5)	44.7 (16.2)
Sex: Female, Male (Count of Participants)
Female	4 26.7%	6 40%	10 66.7%	20 44.4%
Male	11 73.3%	9 60%	5 33.3%	25 55.6%

Outcome Measures

1. Primary Outcome

Title	Complete Wound Healing
Description	Time required for complete epithelialization in days
Time Frame	Post operative day 5 and every other day thereafter

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	PRP	PRP+K
Arm/Group Description	Wounds covered with standard dressings: three layers of paraffin gauze, standard bandages, elastic bandage.	Platelet Rich Plasma (PRP) sprayed onto the wound bed with Calcium Chloride. Wounds covered with same standard dressings used in control group.	Keratinocytes suspended in Platelet Rich Plasma (PRP) sprayed onto the wound bed with Calcium Chloride. Wounds covered with same standard dressings used in control group.
Measure Participants	15	15	15
Mean (Standard Deviation) [Days]	13.9 (2.0)	7.2 (0.8)	5.7 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, PRP, PRP+K
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	Pain
Description	Pain evaluated on a Visual Analog Scale (VAS) from 0 (no pain) to 10 (extreme pain), specifically during dressing replacement.
Time Frame	Post operative day 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	PRP	PRP+K
Arm/Group Description	Wounds covered with standard dressings: three layers of paraffin gauze, standard bandages, elastic bandage.	Platelet Rich Plasma (PRP) sprayed onto the wound bed with Calcium Chloride. Wounds covered with same standard dressings used in control group.	Keratinocytes suspended in Platelet Rich Plasma (PRP) sprayed onto the wound bed with Calcium Chloride. Wounds covered with same standard dressings used in control group.
Measure Participants	15	15	15
Mean (Standard Deviation) [VAS Pain Score]	7.2 (0.7)	1.5 (0.9)	0.4 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, PRP, PRP+K
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	ANOVA
	Comments

Adverse Events

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.