<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02211521</url>
  </required_header>
  <id_info>
    <org_study_id>2013-12-056</org_study_id>
    <nct_id>NCT02211521</nct_id>
  </id_info>
  <brief_title>Comparison of Autologous Platelet-rich Plasma With Hyaluronic Acid for the Treatment of Osteoarthritis of the Knee Joint</brief_title>
  <official_title>Randomized, Double Blind, Comparison Clinical Trial to Test the Efficacy and Safety of Intraarticular Injection of Autologous Platelet-rich Plasma (PRP) for the Treatment of Osteoarthritis of the Knee Joint</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Samsung Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Samsung Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the efficacy of platelet-rich plasma versus&#xD;
      hyaluronic acid intra-articular injections for the treatment of osteoarthritis of knee joint.&#xD;
&#xD;
      The hypothesis is that PRP intra-articular injection is comparable or even better than&#xD;
      hyaluronic acid injection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Osteoarthritis (OA) has a significant impact on our society. The limited regenerative&#xD;
      capacity of cartilage is part of this problem. Existing degenerative lesions lead to&#xD;
      accelerated deterioration of the articular (joint) surface leading to end-stage arthritis. In&#xD;
      particular, the most recent knowledge regarding tissue biology highlights a complex&#xD;
      regulation of growth factors (GFs) for the normal tissue structure and the reaction to tissue&#xD;
      damage. The influence of GFs on cartilage repair is now widely investigated in vitro and in&#xD;
      vivo. Platelet Rich Plasma (PRP) is a simple, low- cost and minimally- invasive method that&#xD;
      allows one to obtain a natural concentrate of autologous GFs from the blood, and it is&#xD;
      increasingly applied in the clinical practice to treat knee degenerative pathology, such as&#xD;
      chondropathy and early OA. The biological rational of PRP is that platelets contain storage&#xD;
      pools of GFs, cytokines, chemokines and many other mediators.Although its widespread&#xD;
      application, there are little high level studies in the literature to demonstrate the real&#xD;
      efficacy of PRP.&#xD;
&#xD;
      The investigators hypothesized that intra-articular injections of PRP to treat knee&#xD;
      osteoarthritis could determine pain relief and recovery of knee function with overall&#xD;
      clinical outcome comparable or even better than viscosupplementation, which is a common&#xD;
      injective approach applied in this kind of pathology. To this purpose the investigators&#xD;
      designed a double blind randomized controlled trial comparing PRP vs viscosupplementation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in International Knee Documentation Committee subjective score at week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>International Knee Documentation Committee subjective score for both groups</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in VAS (Visual Analogue scale) for pain during walking</measure>
    <time_frame>Baseline, Week 6, Week 12, Week 24</time_frame>
    <description>VAS (Visual Analogue scale) for pain during walking for both groups of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Western Ontario and McMaster Universities Arthritis Index</measure>
    <time_frame>Baseline, Week 6, Week 12, Week 24</time_frame>
    <description>Western Ontario and McMaster Universities Arthritis Index variation for both groups&#xD;
Subscale analysis of pain, stiffness, function also contain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events</measure>
    <time_frame>Week 6, Week 12, Week 24</time_frame>
    <description>All adverse events included</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Samsung Medical Center Patellofemoral score (SMC patellofemoral score)</measure>
    <time_frame>Baseline, Week 6, Week 12, Week 24</time_frame>
    <description>Samsung Medical Center Patellofemoral score for both groups of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient global assessment</measure>
    <time_frame>Week 6, Week 12, Week 24</time_frame>
    <description>Patient global assessment was evaluated for improvement of symptoms using 100mm VAS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in International Knee Documentation Committee subjective score at week 6, week 12</measure>
    <time_frame>Baseline, Week 6, Week 12</time_frame>
    <description>International Knee Documentation Committee subjective score for both groups</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Level of white blood cell count of platelet rich plasma</measure>
    <time_frame>baseline</time_frame>
    <description>Assessment of level of WBC, platelet and several growth factors of platelet rich plasma Assessment of level of white blood cell count of platelet rich plasma</description>
  </other_outcome>
  <other_outcome>
    <measure>Level of platelet of platelet rich plasma</measure>
    <time_frame>baseline</time_frame>
    <description>Assessment of level of platelet of platelet rich plasma</description>
  </other_outcome>
  <other_outcome>
    <measure>Level of growth factors of platelet rich plasma</measure>
    <time_frame>baseline</time_frame>
    <description>Assessment of level several growth factors of platelet rich plasma (platelet derived growth factor, transforming growth factor -b1, vascular endothelial growth factor, epidermal growth factor, fibroblast growth factor etc)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">110</enrollment>
  <condition>Osteoarthritis, Knee</condition>
  <arm_group>
    <arm_group_label>PRP group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to this group of treatment will receive 1 blinded knee intra-articular injections of autologous Platelet-Rich Plasma (3ml).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hyaloronan group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomized to this group of treatment will receive 1 blinded knee intra-articular injections of hyaluronic acid (3ml)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PRP</intervention_name>
    <description>3ml of PRP</description>
    <arm_group_label>PRP group</arm_group_label>
    <other_name>GPS III, Biomet Biologics, Warsaw, Ind, USA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hyaluronic acid</intervention_name>
    <description>3ml hyaluronic acid</description>
    <arm_group_label>Hyaloronan group</arm_group_label>
    <other_name>LBSA0103, 60 mg/3ml, LG Life Sciences, Korea</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with osteoarthritis of knee (by American College of Rheumatology Criteria)&#xD;
             and Kellgren-Lawrence grade I ~ III&#xD;
&#xD;
          -  More than 40 out of 100-mm VAS scale for pain at screening and baseline&#xD;
&#xD;
          -  Participant is willing and able to give informed consent for participation in the&#xD;
             study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with Hb values &lt; 10 g/dl and platelet values &lt; 100,000/ul&#xD;
&#xD;
          -  Patients with a current or medical history of autoimmune disease&#xD;
&#xD;
          -  Recent fever ( within 2 weeks) or serious illness&#xD;
&#xD;
          -  Local infection at the site of the procedure&#xD;
&#xD;
          -  Corticosteroid injection at treatment site within 1 month&#xD;
&#xD;
          -  Systematic use of corticosteroids within 2 weeks&#xD;
&#xD;
          -  Female participants who are pregnant, lactating or planning pregnancy during the&#xD;
             course of the study&#xD;
&#xD;
          -  Patients who have been administered with immunosuppressants within the past 6 weeks&#xD;
&#xD;
          -  Patients who are enrolled in any other clinical trials within 4 weeks&#xD;
&#xD;
          -  Patients who the principal investigator considers inappropriate for participation in&#xD;
             the clinical trial for reasons other than those listed above&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chul-WOn Ha, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Samsung Medical Center, Sungkyunkwan University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>135-710</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <reference>
    <citation>Cerza F, Carni S, Carcangiu A, Di Vavo I, Schiavilla V, Pecora A, De Biasi G, Ciuffreda M. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med. 2012 Dec;40(12):2822-7. doi: 10.1177/0363546512461902. Epub 2012 Oct 25.</citation>
    <PMID>23104611</PMID>
  </reference>
  <reference>
    <citation>Spakova T, Rosocha J, Lacko M, Harvanova D, Gharaibeh A. Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil. 2012 May;91(5):411-7. doi: 10.1097/PHM.0b013e3182aab72.</citation>
    <PMID>22513879</PMID>
  </reference>
  <reference>
    <citation>Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A, Fornasari PM, Giannini S, Marcacci M. Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy. 2011 Nov;27(11):1490-501. doi: 10.1016/j.arthro.2011.05.011. Epub 2011 Aug 10.</citation>
    <PMID>21831567</PMID>
  </reference>
  <reference>
    <citation>Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, Fortier LA. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med. 2014 Jan;42(1):35-41. doi: 10.1177/0363546513507766. Epub 2013 Nov 5.</citation>
    <PMID>24192391</PMID>
  </reference>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>July 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 7, 2014</study_first_posted>
  <last_update_submitted>December 9, 2015</last_update_submitted>
  <last_update_submitted_qc>December 9, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 10, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Samsung Medical Center</investigator_affiliation>
    <investigator_full_name>ChulWon Ha</investigator_full_name>
    <investigator_title>Professor of Department of Orthopaedic Surgery</investigator_title>
  </responsible_party>
  <keyword>Osteoarthritis, platelet-rich plasma, hyaluronic acid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyaluronic Acid</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02211521
org study id: 2013-12-056
nct id: NCT02211521
lead sponsor: 
has dmc: Yes
The purpose of this study is to compare the efficacy of platelet-rich plasma versus
      hyaluronic acid intra-articular injections for the treatment of osteoarthritis of knee joint.

      The hypothesis is that PRP intra-articular injection is comparable or even better than
      hyaluronic acid injection.
Osteoarthritis (OA) has a significant impact on our society. The limited regenerative
      capacity of cartilage is part of this problem. Existing degenerative lesions lead to
      accelerated deterioration of the articular (joint) surface leading to end-stage arthritis. In
      particular, the most recent knowledge regarding tissue biology highlights a complex
      regulation of growth factors (GFs) for the normal tissue structure and the reaction to tissue
      damage. The influence of GFs on cartilage repair is now widely investigated in vitro and in
      vivo. Platelet Rich Plasma (PRP) is a simple, low- cost and minimally- invasive method that
      allows one to obtain a natural concentrate of autologous GFs from the blood, and it is
      increasingly applied in the clinical practice to treat knee degenerative pathology, such as
      chondropathy and early OA. The biological rational of PRP is that platelets contain storage
      pools of GFs, cytokines, chemokines and many other mediators.Although its widespread
      application, there are little high level studies in the literature to demonstrate the real
      efficacy of PRP.

      The investigators hypothesized that intra-articular injections of PRP to treat knee
      osteoarthritis could determine pain relief and recovery of knee function with overall
      clinical outcome comparable or even better than viscosupplementation, which is a common
      injective approach applied in this kind of pathology. To this purpose the investigators
      designed a double blind randomized controlled trial comparing PRP vs viscosupplementation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from baseline in International Knee Documentation Committee subjective score at week 24
time frame: Baseline, Week 24
description: International Knee Documentation Committee subjective score for both groups
measure: Change from baseline in VAS (Visual Analogue scale) for pain during walking
time frame: Baseline, Week 6, Week 12, Week 24
description: VAS (Visual Analogue scale) for pain during walking for both groups of treatment
measure: Change from baseline in Western Ontario and McMaster Universities Arthritis Index
time frame: Baseline, Week 6, Week 12, Week 24
description: Western Ontario and McMaster Universities Arthritis Index variation for both groups
Subscale analysis of pain, stiffness, function also contain
measure: Number of Participants with Adverse Events
time frame: Week 6, Week 12, Week 24
description: All adverse events included
measure: Change from baseline in Samsung Medical Center Patellofemoral score (SMC patellofemoral score)
time frame: Baseline, Week 6, Week 12, Week 24
description: Samsung Medical Center Patellofemoral score for both groups of treatment
measure: Patient global assessment
time frame: Week 6, Week 12, Week 24
description: Patient global assessment was evaluated for improvement of symptoms using 100mm VAS.
measure: Change from baseline in International Knee Documentation Committee subjective score at week 6, week 12
time frame: Baseline, Week 6, Week 12
description: International Knee Documentation Committee subjective score for both groups
measure: Level of white blood cell count of platelet rich plasma
time frame: baseline
description: Assessment of level of WBC, platelet and several growth factors of platelet rich plasma Assessment of level of white blood cell count of platelet rich plasma
measure: Level of platelet of platelet rich plasma
time frame: baseline
description: Assessment of level of platelet of platelet rich plasma
measure: Level of growth factors of platelet rich plasma
time frame: baseline
description: Assessment of level several growth factors of platelet rich plasma (platelet derived growth factor, transforming growth factor -b1, vascular endothelial growth factor, epidermal growth factor, fibroblast growth factor etc)
arm group label: PRP group
arm group type: Experimental
description: Patients randomized to this group of treatment will receive 1 blinded knee intra-articular injections of autologous Platelet-Rich Plasma (3ml).
arm group label: Hyaloronan group
arm group type: Active Comparator
description: Patients randomized to this group of treatment will receive 1 blinded knee intra-articular injections of hyaluronic acid (3ml)
intervention type: Biological
intervention name: PRP
description: 3ml of PRP
arm group label: PRP group
other name: GPS III, Biomet Biologics, Warsaw, Ind, USA
intervention type: Drug
intervention name: Hyaluronic acid
description: 3ml hyaluronic acid
arm group label: Hyaloronan group
other name: LBSA0103, 60 mg/3ml, LG Life Sciences, Korea
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Chul-WOn Ha, MD, PhD
role: Principal Investigator
affiliation: Samsung Medical Center, Sungkyunkwan University School of Medicine
facility: 
country: Korea, Republic of
citation: Cerza F, Carni S, Carcangiu A, Di Vavo I, Schiavilla V, Pecora A, De Biasi G, Ciuffreda M. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med. 2012 Dec;40(12):2822-7. doi: 10.1177/0363546512461902. Epub 2012 Oct 25.
PMID: 23104611
citation: Spakova T, Rosocha J, Lacko M, Harvanova D, Gharaibeh A. Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil. 2012 May;91(5):411-7. doi: 10.1097/PHM.0b013e3182aab72.
PMID: 22513879
citation: Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A, Fornasari PM, Giannini S, Marcacci M. Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy. 2011 Nov;27(11):1490-501. doi: 10.1016/j.arthro.2011.05.011. Epub 2011 Aug 10.
PMID: 21831567
citation: Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, Fortier LA. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med. 2014 Jan;42(1):35-41. doi: 10.1177/0363546513507766. Epub 2013 Nov 5.
PMID: 24192391
responsible party type: Principal Investigator
investigator affiliation: Samsung Medical Center
investigator full name: ChulWon Ha
investigator title: Professor of Department of Orthopaedic Surgery
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
mesh term: Hyaluronic Acid