PRP Versus PRF Versus Conventional Treatment in Chronic Non-healing Skin Ulcers

NCT ID: NCT06281483

Last Updated: 2025-03-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-01

Study Completion Date

2026-01-31

Brief Summary

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To compare the therapeutic efficacy of PRP and PRF: two relatively newer modalities in the management of chronic non-healing ulcers versus conventional treatment.

Detailed Description

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An ulcer is a breach in the continuity of skin, epithelium or mucous membrane caused by sloughing out of inflamed necrotic tissue. Chronic ulcers are formed because of the failure in the orderly process that produces anatomic and functional integrity. Ulcers are considered chronic if they show no tendency to heal after six weeks of appropriate treatment or those that have not fully healed after 12 months.

Despite greater understanding of the biology of wound healing over the past 20 years, some chronic wounds, such as venous leg ulcers, pressure ulcers, and diabetic foot ulcers, are recalcitrant to healing.

In addition to local wound-related factors (eg, ischemia, infection) and patient related factors (eg, diabetes, old age, obesity, malnutrition) that can impair healing, reduction in tissue growth factors, an imbalance between proteolytic enzymes and their inhibitors, and the presence of senescent cells seem to be particularly important in chronic wounds.

Regardless of the underlying etiology, non-healing ulcers tend to have chronic pain, discharge, sleep impairment, and subsequent adverse repercussions in quality of life and productivity, and impose a huge economic burden on the medical system.

In the United States, chronic ulcers including decubitus, vascular, inflammatory, and rheumatologic subtypes affect 6 million people, with increasing numbers anticipated in a growing elderly and diabetic populations.

Venous, arterial, and neuropathic ulcers account for up to 90 percent of ulcers. In a survey study in which wound care professionals in Germany reported the etiologies of chronic leg ulcers in over 31,000 patients, venous insufficiency, arterial insufficiency, and mixed venous and arterial insufficiency accounted for 48, 15, and 18 percent of chronic ulcers, respectively. There are multiple less common causes of ulcers, including physical injury, infection, vasculopathy, pyoderma gangrenosum, panniculitis, malignancy, medications.

The characteristics and difficulties in healing chronic ulcers lie in the lack of an adequate blood supply, long-term repeated inflammatory stimulation in the surrounding tissues, and the presence of a dead cavity. For chronic ulcers, the key is to determine the cause, determine the factors that affect the healing process, and create an environment suitable for healing to effectively treat the wound.

Current therapies include debridement, offloading, etc. However, the response to treatment is often poor, and the outcome is disappointing. These wounds place the limb at the risk of infection and amputation and also puts the patients at risk of mortality.

Chronic ulcers are known to have reduced levels of platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, and transforming growth factorβ compared with acute wounds. It has been suggested that growth factors may become trapped by extracellular matrix molecules or may be degraded by proteases to an excessive degree, resulting in non-healing.

Many of the growth factors released from platelets play an important role in the wound-healing process, and topical application of concentrated activated platelets can stimulate wound healing in situations where standard wound care treatments are ineffective.

Platelet-rich concentrates, known as autologous platelet concentrates (APCs), have garnered significant attention in recent years and demonstrate remarkable potential in wound treatment.

Previous studies have shown that activated platelets undergo exocytosis of intracellular granules containing growth factors such as platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and insulin like growth factor (IGF). These growth factors contribute to wound healing by promoting regeneration and wound repair, thereby elucidating the efficacy of APCs therapy in skin regeneration, acne scar treatment, and enhanced wound healing.

APCs can be further classified into platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) based on distinct preparation processes, each with varied clinical applications. PRP, as the first-generation platelet concentrate, is plasma with a high platelet concentration obtained through specific centrifugation of fresh whole blood. PRP contains platelet concentrations four to five times higher than that of whole blood. It has demonstrated positive effects on bone regeneration and wound healing.

PRF, on the other hand, as the second-generation platelet concentrate, exhibits a slow release of growth factors, thereby prolonging their action.

APCs has a greater capacity to modulate the local microenvironment and expedite tissue regeneration. It has also been observed to alleviate pain, accelerate epithelization, and facilitate complete wound healing.

Currently, PRP and PRF, whose therapeutic value is equal to that of stem cells, are currently one of the most promising therapy agents in regenerative medicine. They are increasingly being used in different areas of medicine including aesthetic dermatology, orthopedics, sports medicine and surgery.

Because of the lack of sufficient literature, our study aimed to compare the efficacy of PRP versus PRF versus conventional treatment as a relatively newer modalities in the management of chronic non-healing skin ulcers.

Conditions

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Chronic Non-healing Skin Ulcers

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PRP / Group A

12 patient

Group Type ACTIVE_COMPARATOR

platelet-rich plasma

Intervention Type OTHER

Under aseptic conditions, 20 mL of whole blood will be withdrawn from each patient and will be collected in the centrifuge tube prefilled with Anticoagulant Citrate Dextrose (1.5 mL each). A two-stage centrifugation process (double-spin method) will be employed for the preparation of PRP. The first spin is at 100 relative centrifugal force (RCF) (g) for 10 min, while the second spin is at 400 RCF for 10 min. PRP will be injected into the base of the ulcer and the surrounding skin. Group A: will receive treatment that will include PRP application, conventional debridement, and dressing coverage. Sessions will be repeated weekly for a maximum of eight sessions.

PRF / Group B

12 patient

Group Type ACTIVE_COMPARATOR

platelet-rich fibrin

Intervention Type OTHER

20 ml blood will be drawn from each patient by venipuncture under aseptic precautions in four sterile glass tubes of 5-ml capacity without anticoagulant and immediately centrifuged. A single stage centrifugation process, that is (200 g for 8 min), has been found to produce a fibrin clot with the highest platelet and WBC count and highest overall cumulative growth factor yield. Group B: will receive treatment that will include PRF application, conventional debridement, and dressing coverage. Sessions will be repeated weekly for a maximum of eight sessions.

Group C (the control group)

12 patient

Group Type ACTIVE_COMPARATOR

Surgical debridement, normal saline washing and dressing coverage

Intervention Type OTHER

Each patient will receive the same conventional debridement and dressing coverage (After opening the bandage, the ulcer will be irrigated with normal saline and will be prepared for debridement as required to remove dead tissues and hyperkeratotic skin. Then, a second wash with normal saline will be done to remove any debris), but without any PRP nor PRF application.

Interventions

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platelet-rich plasma

Under aseptic conditions, 20 mL of whole blood will be withdrawn from each patient and will be collected in the centrifuge tube prefilled with Anticoagulant Citrate Dextrose (1.5 mL each). A two-stage centrifugation process (double-spin method) will be employed for the preparation of PRP. The first spin is at 100 relative centrifugal force (RCF) (g) for 10 min, while the second spin is at 400 RCF for 10 min. PRP will be injected into the base of the ulcer and the surrounding skin. Group A: will receive treatment that will include PRP application, conventional debridement, and dressing coverage. Sessions will be repeated weekly for a maximum of eight sessions.

Intervention Type OTHER

platelet-rich fibrin

20 ml blood will be drawn from each patient by venipuncture under aseptic precautions in four sterile glass tubes of 5-ml capacity without anticoagulant and immediately centrifuged. A single stage centrifugation process, that is (200 g for 8 min), has been found to produce a fibrin clot with the highest platelet and WBC count and highest overall cumulative growth factor yield. Group B: will receive treatment that will include PRF application, conventional debridement, and dressing coverage. Sessions will be repeated weekly for a maximum of eight sessions.

Intervention Type OTHER

Surgical debridement, normal saline washing and dressing coverage

Each patient will receive the same conventional debridement and dressing coverage (After opening the bandage, the ulcer will be irrigated with normal saline and will be prepared for debridement as required to remove dead tissues and hyperkeratotic skin. Then, a second wash with normal saline will be done to remove any debris), but without any PRP nor PRF application.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Patients presenting with cutaneous ulcers greater than six weeks of duration and a size ranging between 0.5 and 10 cm, having a normal platelet count and hemoglobin \>10 gm%.

Exclusion Criteria

* Patients with known bleeding disorders, and/or on oral anticoagulant therapy, uncontrolled diabetes, proven malignancy.
* Patients who are pregnant or lactating.
* Patients with actively infected ulcers, clinically defined by purulent discharge, green discoloration or fever, or positive culture, ulcers with exposed bone with no underlying granulation tissue, HIV, HCV, HBV patients.
* Patients who are with unrealistic expectations and unwilling to give consent for treatment or photography.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Helwan University

OTHER

Sponsor Role collaborator

Kafrelsheikh University

OTHER

Sponsor Role lead

Responsible Party

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Mohamed Aboshabana Hussein Mohamed

Assistant Lecturer of Dermatology and Venereology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Heba Mahmoud Diab, Professor

Role: STUDY_CHAIR

Ain Shams University

Locations

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Badr Hospital - Helwan University and Kafrelseikh University Hospital

Cairo, , Egypt

Site Status RECRUITING

Countries

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Egypt

Central Contacts

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Mohamed Aboshabana Hussein, Assistant Lecturer

Role: CONTACT

01007981008

Eman Mohamed Salah, Assistant Prof

Role: CONTACT

Facility Contacts

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Mohamed Aboshabana Hussein, Assistant Lecturer

Role: primary

01007981008

References

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Badran Z, Abdallah MN, Torres J, Tamimi F. Platelet concentrates for bone regeneration: Current evidence and future challenges. Platelets. 2018 Mar;29(2):105-112. doi: 10.1080/09537104.2017.1327656. Epub 2017 Jun 26.

Reference Type BACKGROUND
PMID: 28649897 (View on PubMed)

Chen J, Wan Y, Lin Y, Jiang H. Platelet-rich fibrin and concentrated growth factors as novel platelet concentrates for chronic hard-to-heal skin ulcers: a systematic review and Meta-analysis of randomized controlled trials. J Dermatolog Treat. 2022 Mar;33(2):613-621. doi: 10.1080/09546634.2020.1773386. Epub 2020 Jun 1.

Reference Type BACKGROUND
PMID: 32441168 (View on PubMed)

Dashore S, Chouhan K, Nanda S, Sharma A. Platelet-Rich Fibrin, Preparation and Use in Dermatology. Indian Dermatol Online J. 2021 Nov 25;12(Suppl 1):S55-S65. doi: 10.4103/idoj.idoj_282_21. eCollection 2021 Nov.

Reference Type BACKGROUND
PMID: 34976881 (View on PubMed)

Evans AG, Ivanic MG, Botros MA, Pope RW, Halle BR, Glassman GE, Genova R, Al Kassis S. Rejuvenating the periorbital area using platelet-rich plasma: a systematic review and meta-analysis. Arch Dermatol Res. 2021 Nov;313(9):711-727. doi: 10.1007/s00403-020-02173-z. Epub 2021 Jan 12.

Reference Type BACKGROUND
PMID: 33433716 (View on PubMed)

Muthuprabakaran K, Pai VV, Ahmad S, Shukla P. A cross-sectional analysis of the effects of various centrifugation speeds and inclusion of the buffy coat in platelet-rich plasma preparation. Indian J Dermatol Venereol Leprol. 2021 Nov-Dec;87(6):792-799. doi: 10.25259/IJDVL_1050_20.

Reference Type BACKGROUND
PMID: 34245527 (View on PubMed)

Other Identifiers

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APCs in chronic skin ulcers

Identifier Type: -

Identifier Source: org_study_id

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