Clinical Efficacy of Platelet Gel From Cord Blood for the Treatment of Diabetic Foot Ulcers

NCT02389010 | Completed Phase 3

• 1 other identifier: 1-2014
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 9

Brief Summary

A novel method (PCT n. WO 2010/007502 A2, 2010) has been developed to obtain platelet gel from umbilical cord blood (CBPG). The main advantages so far identified in CBPG as compared to platelet gel derived from adult platelets relate to the lack of microbiological contamination in the former and to a different profile of growth factors concentrations, such as a higher content of VEGF and lower content of TGF in CBPG. Recent developments have led to a procedure in which CBPG can be prepared, stored in a cryopreservation bag and applied to the skin ulcer without breaking the sterility chain. In spite of promising results on allogeneic CBPG, a randomized clinical trial of sufficient statistical power to detect significant advantages (clinical and economical) will be performed in patients affected by diabetic foot ulcers and randomly treated with CBPG versus standard local medications (SLM).This study is a multicenter (8 centers) controlled randomized clinical trial. Outcomes: (1) primary objective is to evaluate the number of closed skin ulcers within 4 weeks of treatment with CBPG vs standard local medications; (2) secondary objectives are percent skin ulcer closure area, number and type of adverse events and cost of treatment. Sample size calculation: 95 + 5 (dropout) test and 95 + 5 (dropout) control patients ensure 80% power to detect as statistically significant (p\<0.05) \>60% healing in test vs 40% healing in control.Each clinical centre has been invited to enrol 15 treated and 15 control patients, according to local availability in 12 months. CB units are routinely collected after mother's informed consent before and after placenta delivery in accredited public cord blood banks belonging to the Italian Cord Blood Network (ITCBN) coordinated by the Centro Nazionale Sangue (CNS). After storage and transportation at monitored room temperature, the units will be processed for the preparation of CBPG within 48 hours of collection. CBPG will be prepared according to standard procedures with a defined final platelet concentration (0.8-1.2 x 109/L). The CBPC units will be finally cryopreserved in a -80°C freezer in view of the clinical use of the CBPG, which will require thawing at 37°C in a waterbath and activation with Calcium gluconate. For SLM, each clinical center will use their validated standard procedures.

Conditions

Diabetic Foot Ulcers

Keywords

Umbilical Cord Blood; Diabetic Foot; Ulcer; Cost; Effectiveness; Safety; Platelet Gel; Cord Blood Platelet Gel; Adverse Event

Outcome Measures

Primary Outcomes (1)

• Number of closed skin ulcers within 4 weeks of treatment with cord blood platelet gel (CBPG) vs standard local medications

  The major end-point will be to test feasibility and compare efficacy of treating diabetic foot skin ulcers (Texas C I-II) with allogeneic CBPG versus SLM and their respective costs. The primary outcome measures will be: number of healed wounds after 4 weeks of CBPG treatment versus control and time to achieve complete closure. Lesions will be assessed two times per week. Wounds with less than 50% closure after 4 weeks will be considered as a failure. The main target will be to validate the clinical use of an allogeneic product matching several requirements: to comply with routine process of periodic blood collection and blood component preparation; to maintain closed and aseptic conditions through the entire process; to contain platelet growth factor concentrations reported to be clinically effective; to be suitable to treat one medium-size ulcer per aliquot, defined as 'CBPG unit' (on average 10 mL of CB plasma containing 10 billion platelets); to be ABO compatible with the patient.

  4 weeks

Secondary Outcomes (3)

• Percent skin ulcer closure area

  4 weeks

• Number and type of adverse events

  4 weeks

• Cost of treatment

  4 weeks

Study Arms (2)

Allogeneic Cord Blood Platelet Gel-CBPG

EXPERIMENTAL

For the medication of patients, one CBPG unit (mean volume 10 mL, range 5-15; mean platelet concentration 1 x 109/L, range 0.8 - 1.2 x 109/L. 10 mL in plasma) will be administered every 3-4 days. CBPG units, cryopreserved and stored in a plastic bag in a -80°C freezer, will be thawed at 37°C in a waterbath and activated with Calcium gluconate and immediately transported to sites of clinical use and applied to the skin ulcer without breaking the sterility chain.

Biological: Allogeneic cord blood platelet gel-CBPG

Standard Local Medications-SLM

ACTIVE COMPARATOR

1 administration every 3-4 days for 4 weeks. Each clinical center will use their validated standard local medications. Details and specifications of the local standard medication procedures will be collected from each participating centre.

Other: Standard Local Medications-SLM

Interventions

Allogeneic cord blood platelet gel-CBPG BIOLOGICAL

For the medication of patients, one CBPG unit (mean volume 10 mL, range 5-15; mean platelet concentration 1 x 109/L, range 0.8 - 1.2 x 109/L. 10 mL in plasma) will be administered every 3-4 days. CBPG units, cryopreserved and stored in a plastic bag in a -80°C freezer, will be thawed at 37°C in a waterbath and activated with Calcium gluconate and immediately transported to sites of clinical use and applied to the skin ulcer without breaking the sterility chain.

Allogeneic Cord Blood Platelet Gel-CBPG

Standard Local Medications-SLM OTHER

Each clinical center will use their validated standard local medications. Details and specifications of the local standard medication procedures will be collected from each participating centre.

Standard Local Medications-SLM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Patient with diabetic foot ulcers
• Size of ulcer (5 cm\^2 \< X \< 30 cm\^2)
• Absence of undermining or tunneling
• TUC I and II C. At the time of 1st application, ulcer is not clinically infected (smelly, perilesional edematous tissue, hot and flushed)
• Effective Revascularization ( TcPO2 foot \>30 mmHg and Patency of one or more tibial arteries until the ankle/foot)
• Informed consent
• Patient able to understand the conditions of the study and to participate for its entire duration

You may not qualify if:

• Patient with serious medical conditions that contraindicate the patient's participation in the study
• Ineffective revascularization
• Heel ulcer and outcomes of amputation
• Patient with present clinical infection
• Bone and/or sinew exposure
• Current pregnancy
• Use of experimental drugs.
• Negative Pressure (possible use in control arm patients)

Sponsors & Collaborators

• Centro Nazionale Sangue: lead
• Italian National Cord Blood Network: collaborator

Study Sites (9)

Ospedaliero-Universitaria di Bologna

Bologna, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Italy

Location

Presidio Ospedaliero "Spirito Santo"

Pescara, Italy

Location

Azienda Ospedalero-Universitaria Pisana

Pisa, Italy

Location

Presidio Ospedaliero "E. Morelli"

Reggio Calabria, Italy

Location

Policlinico Umberto I - "Sapienza" Università di Roma

Roma, Italy

Location

Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

A.O.U. Citta della Salute e della Scienza di Torino

Torino, Italy

Location

Hospital de la Santa Creu i Sant Pau - Servicio de Angiología, Cirugía Vascular y Endovascular

Barcelona, Catalonia, 08026, Spain

Location

Related Publications (10)

• Rosso L, Parazzi V, Damarco F, Righi I, Santambrogio L, Rebulla P, Gatti S, Ferrero S, Nosotti M, Lazzari L. Pleural tissue repair with cord blood platelet gel. Blood Transfus. 2014 Jan;12 Suppl 1(Suppl 1):s235-42. doi: 10.2450/2013.0214-12. Epub 2013 May 14.

  PMID: 23736928 RESULT

• Parazzi V, Lazzari L, Rebulla P. Platelet gel from cord blood: a novel tool for tissue engineering. Platelets. 2010;21(7):549-54. doi: 10.3109/09537104.2010.514626.

  PMID: 20873963 RESULT

• Giusti I, Rughetti A, D'Ascenzo S, Millimaggi D, Pavan A, Dell'Orso L, Dolo V. Identification of an optimal concentration of platelet gel for promoting angiogenesis in human endothelial cells. Transfusion. 2009 Apr;49(4):771-8. doi: 10.1111/j.1537-2995.2008.02033.x. Epub 2008 Dec 23.

  PMID: 19170984 RESULT

• Mishra A, Woodall J Jr, Vieira A. Treatment of tendon and muscle using platelet-rich plasma. Clin Sports Med. 2009 Jan;28(1):113-25. doi: 10.1016/j.csm.2008.08.007.

  PMID: 19064169 RESULT

• Spyridakis M, Christodoulidis G, Chatzitheofilou C, Symeonidis D, Tepetes K. The role of the platelet-rich plasma in accelerating the wound-healing process and recovery in patients being operated for pilonidal sinus disease: preliminary results. World J Surg. 2009 Aug;33(8):1764-9. doi: 10.1007/s00268-009-0046-y.

  PMID: 19424751 RESULT

• O'Connell SM, Impeduglia T, Hessler K, Wang XJ, Carroll RJ, Dardik H. Autologous platelet-rich fibrin matrix as cell therapy in the healing of chronic lower-extremity ulcers. Wound Repair Regen. 2008 Nov-Dec;16(6):749-56. doi: 10.1111/j.1524-475X.2008.00426.x.

  PMID: 19128245 RESULT

• Gope ML, Gope R. Tyrosine phosphorylation of EGF-R and PDGF-R proteins during acute cutaneous wound healing process in mice. Wound Repair Regen. 2009 Jan-Feb;17(1):71-9. doi: 10.1111/j.1524-475X.2008.00443.x.

  PMID: 19152653 RESULT

• Nikolidakis D, Jansen JA. The biology of platelet-rich plasma and its application in oral surgery: literature review. Tissue Eng Part B Rev. 2008 Sep;14(3):249-58. doi: 10.1089/ten.teb.2008.0062.

  PMID: 18601587 RESULT

• 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. doi: 10.1097/00000658-198609000-00011.

  PMID: 3753059 RESULT

• Knighton DR, Ciresi K, Fiegel VD, Schumerth S, Butler E, Cerra F. Stimulation of repair in chronic, nonhealing, cutaneous ulcers using platelet-derived wound healing formula. Surg Gynecol Obstet. 1990 Jan;170(1):56-60.

  PMID: 2403699 RESULT

Related Links

• Competent authority website

MeSH Terms

Conditions

Diabetic Foot; Ulcer

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Maurizio Marconi, MD

  Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

  PRINCIPAL INVESTIGATOR

• Simonetta Pupella, MD

  Centro Nazionale Sangue

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2015
• First Posted: March 17, 2015
• Study Start: January 1, 2015
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: July 21, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (8); ES (1)