Registry Trial of the Effectiveness of Platelet Rich Plasma for Chronic Non-Healing Wounds (CMS)

Effectiveness of Autologous Platelet Rich Plasma in the Treatment of Chronic Skin Wounds

This study will examine differences in the process of wound-healing in patients treated with platelet rich plasma (a concentration of proteins derived from a patients own blood) applied to the wound as a gel; injected into the wound or surrounding tissue; or both; compared to patients treated with usual medical treatment . This study seeks to enroll patients who are 18 or older with a non-healing skin wound that is at least 30 days old. Only patients with Diabetic Foot Ulcers, Venous Ulcers, or Pressure Ulcers will be included in the study.

Study Overview

• Status: Terminated
• Conditions: Diabetic Foot Ulcers; Pressure Ulcers; Venous Ulcers
• Intervention / Treatment: Device: Autologous PRP Gel; Procedure: Standard Wound Care; Device: Autologous PRP Injections; Device: Autologous PRP Gel plus PRP Injections

Detailed Description

The proposed investigation is designed to solicit a large number of patients (N=1,500) with non-healing wounds (Diabetic Foot Ulcers, Venous Ulcers, or Pressure Ulcers) that have not responded to standard wound care in the previous 30 days or more. A prospective, interventional, single-blinded, controlled, registry trial will be used. Data will be analyzed to compare patients who received PRP therapy (PRP gel application, PRP injection, or both) and standard wound care (usual customary care) with patients who received standard wound care (usual customary care), only. Wound size, rate of healing, quality of life, and recurrence of wound will be measured during the 16-week period at usual office visits.

Hypotheses to be tested:

1. Treatment of a chronic wound with standard of care and autologous platelet rich plasma (PRP) will increase the velocity of healing (rate of wound closure) over a twenty week period as compared to patients receiving standard wound care only (Control Group), which results in the patient's ability to return to previous function and resumption of normal activities.
2. Treatment of a chronic wound with standard of care and autologous platelet rich plasma (PRP) will result in complete wound healing within twenty weeks, whereas complete wound healing will not be observed within twenty weeks in patients receiving standard wound care only (Control Group).

• Study Type: Interventional
• Enrollment (Anticipated): 1500
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Bakersfield, California, United States, 93313
      • Good Samaritan Wound Care Center
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Sunnyside Foot and Ankle
  • New Jersey
    • Englewood, New Jersey, United States, 07631
      • Wound Care Center, Englewood Hospital and Medical Center
  • New York
    • Lake Success, New York, United States, 11042
      • Comprehensive Wound Healing Center and Hyperbarics
  • Ohio
    • Cleveland, Ohio, United States, 44107
      • Total Foot Care
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Heritage Valley Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Medicare Eligible
• Written informed consent obtained from either the subject or the subject's legally acceptable representative prior to screening activities
• Male or female ≥ 18 years of age
• Duration of Diabetic Foot Ulcers (DFU),Venous Ulcers (VU), or Pressure Ulcers (PU) is greater than 30 days at first visit/subject screening
• DFU is classified as Wagner 1 -2 on the Wagner classification system
• If more than one non-healing wound is present, the largest of the wounds that is classified as a Wagner 1 - 2.
• If a subject has multiple eligible wounds, the largest wound will be selected. There must be at least 4 cm between the index wound and other wounds; if all wounds are closer than 4 cm, the subject should not be enrolled (screen failure).
• The ulcer must be clinically non-infected
• Able and willing to comply with the procedures required by the protocol. Subjects may be managed as either inpatient or outpatient.
• If a female of childbearing potential, the subject must have a negative urine pregnancy test at screening and must agree to use adequate contraception methods for the duration of the study.
• Ankle Brachial Index (ABI) greater than or equal to 0.7.

Exclusion Criteria:

• Subjects with known sensitivity to components of the Arteriocyte BioBandage™ (calcium chloride, thrombin, acid citrate dextrose solution A (ACDA)).
• Current treatment of another chronic wound in the same limb (defined as arm or leg).
• Wound is not of DFU, PU, or VU pathophysiology.
• PU is classified as late stage III or stage IV.
• Confirmed presence of osteomyelitis, or if osteomyelitis is suspected.
• Received systemic corticosteroids or immunosuppressive agents, hyperbaric oxygen therapy (HBOT), electrostimulation, growth factors, or any cell or tissue-derived products for wounds during the 30 days preceding the screening visit.
• Any chronic condition requiring the use of systemic corticosteroids 30 days prior to study entry and anytime during the course of the study.
• Received radiation therapy or chemotherapy within previous 6 months.
• Any malignancy other than non-melanoma skin cancer.
• Patient has radiographic evidence consistent with diagnosis of neuropathic osteoarthropathy (Charcot foot) in the treatment limb.
• Ulcer area decreases by greater than or equal to 30% during screening period
• Subjects who are cognitively impaired and do not have a healthcare proxy.
• Subject has inadequate venous access for repeated blood draw required for PRP preparation.
• Subject has sickle cell anemia.
• Subject is pregnant or plans to become pregnant during the duration of the trial.
• Concurrent participation in a clinical trial in which an investigational agent is used.
• Females who are nursing.
• Subjects with Thrombocytopenia < 100,000 platelets/µL.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous PRP Gel; The method of application for PRP treatment will be decided by the clinician in accordance with the appearance of the wound bed. The application of topical PRP gel may be used in chronic wounds possessing an open, moist wound bed according to following treatment schedule: Baseline/Week 0, Week 1, Week 2, Week 3, Week 7, and Week 11. The Arteriocyte Magellan® System (510(k) cleared) will be used to prepare the autologous PRP gel. For data analysis, the data from these patients will be classified as PRP Treatment Group (Topical application) data.	Device: Autologous PRP Gel; Autologous PRP Gel is prepared using the Arteriocyte Magellan® System (510(k) approved), an Autologous Platelet Separator Instrument, which is a microprocessor-controlled centrifuge designed to be used in the clinical laboratory or intraoperatively at point of care for the safe and rapid preparation of platelet poor plasma and platelet concentrate (platelet rich plasma) from a small sample of blood. The Arteriocyte Magellan® automatically and quickly separates PRP from anticoagulated blood and dispenses it into a separate sterile syringe. The prepared PRP is then activated (by mixing with thrombin and calcium chloride) and sprayed directly on the area to be treated.; Procedure: Standard Wound Care; Subjects in the control group will receive Standard Wound Care treatment for chronic wounds according to accepted medical practices.
Experimental: Autologous PRP Injections; The method of application for PRP treatment will be decided by the clinician in accordance with the appearance of the wound bed. Autologous PRP Injections may be used where chronic wounds possess a raised, hyperproliferative wound margin and/or plaque, according to following treatment schedule: Baseline/Week 0, Week 1, Week 2, Week 3, Week 7, and Week 11. The Arteriocyte Magellan® System (510(k) cleared) will be used to prepare Autologous PRP for injections. For data analysis, the data from these patients will be classified as PRP Treatment Group (Direct Injection) data.	Procedure: Standard Wound Care; Subjects in the control group will receive Standard Wound Care treatment for chronic wounds according to accepted medical practices.; Device: Autologous PRP Injections; Autologous PRP Gel is prepared using the Arteriocyte Magellan® System (510(k) approved), an Autologous Platelet Separator Instrument, which is a microprocessor-controlled centrifuge designed to be used in the clinical laboratory or intraoperatively at point of care for the safe and rapid preparation of platelet poor plasma and platelet concentrate (platelet rich plasma) from a small sample of blood. The Arteriocyte Magellan® automatically and quickly separates PRP from anticoagulated blood and dispenses it into a separate sterile syringe. The prepared PRP is then drawn into multiple small syringes and injected directly into the wound bed or the skin surrounding it.
Experimental: Autologous PRP Gel plus PRP Injections; The method of application for PRP treatment will be decided by the clinician in accordance with the appearance of the wound bed. Some wounds may be suitable for both Autologous PRP Gel plus PRP Injections. Autologous PRP injections into, or to the periphery of, a moist wound bed in which no scarification or raised wound margin is apparent (where autologous PRP Gel can also be used) may further augment wound healing by addressing wound healing in multiple areas, following the treatment schedule: Baseline/Week 0, Week 1, Week 2, Week 3, Week 7, and Week 11. The Arteriocyte Magellan® System (510(k) cleared) will be used to prepare the autologous PRP gel. For data analysis, the data from these patients will be classified as PRP Treatment Group (Topical and Direct) data.	Device: Autologous PRP Gel; Autologous PRP Gel is prepared using the Arteriocyte Magellan® System (510(k) approved), an Autologous Platelet Separator Instrument, which is a microprocessor-controlled centrifuge designed to be used in the clinical laboratory or intraoperatively at point of care for the safe and rapid preparation of platelet poor plasma and platelet concentrate (platelet rich plasma) from a small sample of blood. The Arteriocyte Magellan® automatically and quickly separates PRP from anticoagulated blood and dispenses it into a separate sterile syringe. The prepared PRP is then activated (by mixing with thrombin and calcium chloride) and sprayed directly on the area to be treated.; Procedure: Standard Wound Care; Subjects in the control group will receive Standard Wound Care treatment for chronic wounds according to accepted medical practices.; Device: Autologous PRP Injections; Autologous PRP Gel is prepared using the Arteriocyte Magellan® System (510(k) approved), an Autologous Platelet Separator Instrument, which is a microprocessor-controlled centrifuge designed to be used in the clinical laboratory or intraoperatively at point of care for the safe and rapid preparation of platelet poor plasma and platelet concentrate (platelet rich plasma) from a small sample of blood. The Arteriocyte Magellan® automatically and quickly separates PRP from anticoagulated blood and dispenses it into a separate sterile syringe. The prepared PRP is then drawn into multiple small syringes and injected directly into the wound bed or the skin surrounding it.; Device: Autologous PRP Gel plus PRP Injections; Autologous PRP Gel is prepared using the Arteriocyte Magellan® System (510(k) approved), an Autologous Platelet Separator Instrument, which is a microprocessor-controlled centrifuge designed to be used in the clinical laboratory or intraoperatively at point of care for the safe and rapid preparation of platelet poor plasma and PRP from a small sample of blood. The Arteriocyte Magellan® automatically and quickly separates PRP from anticoagulated blood and dispenses it into a separate sterile syringe. The prepared PRP is then divided into equal parts and half is drawn into multiple small syringes and injected directly into the skin surrounding the wound bed, half is activated (by mixing with thrombin and calcium chloride) and sprayed the wound bed.
No Intervention: Standard Wound Care; Subjects in the control group will receive Standard Wound Care treatment for chronic wounds according to accepted medical practices. For data analysis, the data from these patients will be classified as Control (Standard of Care) Group data

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound Size	Wound size will be measured with ruler/probe for length, width and depth as well as with digital imaging. Wound size will be assessed in digital images taken of the wound.	16 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of wound closure (change in wound size over time)	The ratio of wound percent change over time will be used	16 weeks
Complete wound healing	Complete wound healing is determined when the wound shows no sign of drainage for two consecutive visits (over two weeks)	16 weeks
Health Related Quality of Life	The Center for Disease Control (CDC) Health Related Quality of Life (HRQoL)-14, "Healthy Days Measure" will be administered	16 weeks
Wound recurrence	Incidence of wound recurrence over the course of 16 weeks	16 weeks

Collaborators and Investigators

• Sponsor: Arteriocyte, Inc.
• Investigators: Study Director: Brittany Hamilton, Compass Biomedical (Formerly Arteriocyte, Inc.)

Publications and helpful links

General Publications

• Mustoe TA, O'Shaughnessy K, Kloeters O. Chronic wound pathogenesis and current treatment strategies: a unifying hypothesis. Plast Reconstr Surg. 2006 Jun;117(7 Suppl):35S-41S. doi: 10.1097/01.prs.0000225431.63010.1b.
• Martinez-Zapata MJ, Marti-Carvajal AJ, Sola I, Exposito JA, Bolibar I, Rodriguez L, Garcia J. Autologous platelet-rich plasma for treating chronic wounds. Cochrane Database Syst Rev. 2012 Oct 17;10:CD006899. doi: 10.1002/14651858.CD006899.pub2.
• Lacci KM, Dardik A. Platelet-rich plasma: support for its use in wound healing. Yale J Biol Med. 2010 Mar;83(1):1-9.
• Crovetti G, Martinelli G, Issi M, Barone M, Guizzardi M, Campanati B, Moroni M, Carabelli A. Platelet gel for healing cutaneous chronic wounds. Transfus Apher Sci. 2004 Apr;30(2):145-51. doi: 10.1016/j.transci.2004.01.004.
• 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. doi: 10.1111/j.1537-2995.2004.03366.x.
• Shan GQ, Zhang YN, Ma J, Li YH, Zuo DM, Qiu JL, Cheng B, Chen ZL. Evaluation of the effects of homologous platelet gel on healing lower extremity wounds in patients with diabetes. Int J Low Extrem Wounds. 2013 Mar;12(1):22-9. doi: 10.1177/1534734613477113.
• Yang HS, Shin J, Bhang SH, Shin JY, Park J, Im GI, Kim CS, Kim BS. Enhanced skin wound healing by a sustained release of growth factors contained in platelet-rich plasma. Exp Mol Med. 2011 Nov 30;43(11):622-9. doi: 10.3858/emm.2011.43.11.070.
• Driver VR, Hanft J, Fylling CP, Beriou JM; Autologel Diabetic Foot Ulcer Study Group. A prospective, randomized, controlled trial of autologous platelet-rich plasma gel for the treatment of diabetic foot ulcers. Ostomy Wound Manage. 2006 Jun;52(6):68-70, 72, 74 passim.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): January 1, 2018
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: February 20, 2014
• First Submitted That Met QC Criteria: February 25, 2014
• First Posted (Estimate): February 26, 2014

Study Record Updates

• Last Update Posted (Actual): January 16, 2018
• Last Update Submitted That Met QC Criteria: January 11, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Chronic; Non-healing; Wounds
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Varicose Veins; Diabetic Foot; Foot Ulcer; Ulcer; Varicose Ulcer; Pressure Ulcer
• Other Study ID Numbers: ART-13-006; CAG-00190R3 (Other Identifier: CMS)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No