<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/NCT03290365</url>
  </required_header>
  <id_info>
    <org_study_id>PRP and HA for OA knee</org_study_id>
    <nct_id>NCT03290365</nct_id>
  </id_info>
  <brief_title>The Combination Effect of Platelet-rich Plasma and Hyaluronic Acid for Knee Osteoarthritis</brief_title>
  <official_title>The Combination Long-term Effect of Platelet-rich Plasma and Hyaluronic Acid in Patients With Knee Osteoarthritis: a Prospective Randomized Double-blind Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tri-Service General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tri-Service General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Although platelet rich plasma (PRP) and Hyaluronic acid (HA) are beneficial for&#xD;
      osteoarthritis of knee (OA knee), the combined effect of PRP with HA was not clear so far.&#xD;
      Hence, investigator assess a prospective randomized double-blind controlled trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with single or bilateral OA knee will be enrolled and randomized into intervention&#xD;
      and control group. One dose of PRP is applied into both groups. One week later, one dose of&#xD;
      HA is injected in intervention group and one dose of normal saline is injected in control&#xD;
      group. Outcome measurements included visual analog scale (VAS)、Lequesne's severity&#xD;
      index、Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)、balance test&#xD;
      (Biodex) and analysis of synovial fluid at different follow-up frame (1st month, 3rd month,&#xD;
      6th month and 1 year after treatment).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2018</start_date>
  <completion_date type="Actual">July 1, 2021</completion_date>
  <primary_completion_date type="Actual">July 1, 2021</primary_completion_date>
  <phase>N/A</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in severity of symptoms and functional status on 1st month, 3rd month, 6th month and one year after injection.</measure>
    <time_frame>Pre-treatment, 1st month, 3rd month, 6th month and one year after injection.</time_frame>
    <description>Using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) to measure the symptoms and functional status before treatment and multiple time frame after treatment. Both subscales has the scores ranged from 1 to 5 for each item and a higher score indicating more severe of symptom or impaired functional status.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in severity of symptoms and functional status on 1st month, 3rd month, 6th month and one year after injection.</measure>
    <time_frame>Pre-treatment, 1st month, 3rd month, 6th month and one year after injection.</time_frame>
    <description>Using the Lequesne's severity index to measure the symptoms and functional status before treatment and multiple time frame after treatment. A higher score indicate more severe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of pain on 1st month, 3rd month, 6th month and one year after injection.</measure>
    <time_frame>Pre-treatment, 1st month, 3rd month, 6th month and one year after injection.</time_frame>
    <description>Using the Visual analog scale (VAS) to measure the pain scale before treatment and multiple time frame after treatment. The score ranging from 10 (remarkable pain) to 0 (no pain).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in balance function on 1st month, 3rd month, 6th month and one year after injection.</measure>
    <time_frame>Pre-treatment, 1st month, 3rd month, 6th month and one year after injection.</time_frame>
    <description>Using the balance test (Biodex) to measure the balance function before treatment and multiple time frame after treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in analysis of synovial fluid on 6th month and one year after injection.</measure>
    <time_frame>Pre-treatment, 6th month and one year after injection.</time_frame>
    <description>The synovial fluid is aspirated to measure the parameters before treatment and multiple time frame after treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Knee Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>Platelet rich plasma + Hyaluronic acid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Platelet rich plasma (PRP) and Hyaluronic acid (HA) are beneficial for patients with osteoarthritis of knee. Patients received one dose of PRP injection. One week later, the one dose of HA is injected for intervention group.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Platelet rich plasma + normal saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients received one dose of PRP injection. One week later, the one dose of normal saline is injected for control group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>platelet rich plasma + Hyaluronic acid</intervention_name>
    <description>Platelet rich plasma (PRP) and Hyaluronic acid (HA) are beneficial for patients with osteoarthritis of knee.</description>
    <arm_group_label>Platelet rich plasma + Hyaluronic acid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>platelet rich plasma + normal saline</intervention_name>
    <description>The normal salin as the placebo intervention was injection control group.</description>
    <arm_group_label>Platelet rich plasma + normal saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age between 50 to 75 y/o.&#xD;
&#xD;
          2. Alert consciousness&#xD;
&#xD;
          3. Symptom of knee osteoarthritis persist at least 6 months and stage I to III scored by&#xD;
             Ahlbäck grading system&#xD;
&#xD;
          4. The pain score measured by VAS at least 4 points&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has received hyaluronic acid, PRP or steroid injection within 6 months&#xD;
&#xD;
          2. Has received NSAIDs or steroid within one week&#xD;
&#xD;
          3. Tumor or metastasis surrounding the knee joint&#xD;
&#xD;
          4. Has received total knee replacement, major surgery in knee, rheumatoid arthritis&#xD;
&#xD;
          5. Patient who cant tolerance the balance test.&#xD;
&#xD;
          6. Thrombocytopenia or coagulopathy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yung-Tsan Wu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, National Defense Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital</name>
      <address>
        <city>Taipei</city>
        <state>Neihu District</state>
        <zip>886</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <results_reference>
    <citation>Abate M, Verna S, Schiavone C, Di Gregorio P, Salini V. Efficacy and safety profile of a compound composed of platelet-rich plasma and hyaluronic acid in the treatment for knee osteoarthritis (preliminary results). Eur J Orthop Surg Traumatol. 2015 Dec;25(8):1321-6. doi: 10.1007/s00590-015-1693-3. Epub 2015 Sep 24.</citation>
    <PMID>26403468</PMID>
  </results_reference>
  <results_reference>
    <citation>Lana JF, Weglein A, Sampson SE, Vicente EF, Huber SC, Souza CV, Ambach MA, Vincent H, Urban-Paffaro A, Onodera CM, Annichino-Bizzacchi JM, Santana MH, Belangero WD. Randomized controlled trial comparing hyaluronic acid, platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee. J Stem Cells Regen Med. 2016 Nov 29;12(2):69-78. doi: 10.46582/jsrm.1202011. eCollection 2016.</citation>
    <PMID>28096631</PMID>
  </results_reference>
  <results_reference>
    <citation>Chen SH, Kuan TS, Kao MJ, Wu WT, Chou LW. Clinical effectiveness in severe knee osteoarthritis after intra-articular platelet-rich plasma therapy in association with hyaluronic acid injection: three case reports. Clin Interv Aging. 2016 Sep 8;11:1213-1219. doi: 10.2147/CIA.S114795. eCollection 2016.</citation>
    <PMID>27660427</PMID>
  </results_reference>
  <results_reference>
    <citation>Dallari D, Stagni C, Rani N, Sabbioni G, Pelotti P, Torricelli P, Tschon M, Giavaresi G. Ultrasound-Guided Injection of Platelet-Rich Plasma and Hyaluronic Acid, Separately and in Combination, for Hip Osteoarthritis: A Randomized Controlled Study. Am J Sports Med. 2016 Mar;44(3):664-71. doi: 10.1177/0363546515620383. Epub 2016 Jan 21.</citation>
    <PMID>26797697</PMID>
  </results_reference>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 21, 2017</study_first_posted>
  <last_update_submitted>July 10, 2021</last_update_submitted>
  <last_update_submitted_qc>July 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tri-Service General Hospital</investigator_affiliation>
    <investigator_full_name>Yung-Tsan Wu</investigator_full_name>
    <investigator_title>Attending Physician</investigator_title>
  </responsible_party>
  <keyword>Platelet rich plasma</keyword>
  <keyword>Osteoarthritis of knee</keyword>
  <keyword>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/NCT03290365
org study id: PRP and HA for OA knee
nct id: NCT03290365
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Although platelet rich plasma (PRP) and Hyaluronic acid (HA) are beneficial for
      osteoarthritis of knee (OA knee), the combined effect of PRP with HA was not clear so far.
      Hence, investigator assess a prospective randomized double-blind controlled trial.
Patients with single or bilateral OA knee will be enrolled and randomized into intervention
      and control group. One dose of PRP is applied into both groups. One week later, one dose of
      HA is injected in intervention group and one dose of normal saline is injected in control
      group. Outcome measurements included visual analog scale (VAS)、Lequesne's severity
      index、Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)、balance test
      (Biodex) and analysis of synovial fluid at different follow-up frame (1st month, 3rd month,
      6th month and 1 year after treatment).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change from baseline in severity of symptoms and functional status on 1st month, 3rd month, 6th month and one year after injection.
time frame: Pre-treatment, 1st month, 3rd month, 6th month and one year after injection.
description: Using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) to measure the symptoms and functional status before treatment and multiple time frame after treatment. Both subscales has the scores ranged from 1 to 5 for each item and a higher score indicating more severe of symptom or impaired functional status.
measure: Change from baseline in severity of symptoms and functional status on 1st month, 3rd month, 6th month and one year after injection.
time frame: Pre-treatment, 1st month, 3rd month, 6th month and one year after injection.
description: Using the Lequesne's severity index to measure the symptoms and functional status before treatment and multiple time frame after treatment. A higher score indicate more severe.
measure: Change from baseline of pain on 1st month, 3rd month, 6th month and one year after injection.
time frame: Pre-treatment, 1st month, 3rd month, 6th month and one year after injection.
description: Using the Visual analog scale (VAS) to measure the pain scale before treatment and multiple time frame after treatment. The score ranging from 10 (remarkable pain) to 0 (no pain).
measure: Change from baseline in balance function on 1st month, 3rd month, 6th month and one year after injection.
time frame: Pre-treatment, 1st month, 3rd month, 6th month and one year after injection.
description: Using the balance test (Biodex) to measure the balance function before treatment and multiple time frame after treatment.
measure: Change from baseline in analysis of synovial fluid on 6th month and one year after injection.
time frame: Pre-treatment, 6th month and one year after injection.
description: The synovial fluid is aspirated to measure the parameters before treatment and multiple time frame after treatment.
arm group label: Platelet rich plasma + Hyaluronic acid
arm group type: Active Comparator
description: Platelet rich plasma (PRP) and Hyaluronic acid (HA) are beneficial for patients with osteoarthritis of knee. Patients received one dose of PRP injection. One week later, the one dose of HA is injected for intervention group.
arm group label: Platelet rich plasma + normal saline
arm group type: Placebo Comparator
description: Patients received one dose of PRP injection. One week later, the one dose of normal saline is injected for control group.
intervention type: Drug
intervention name: platelet rich plasma + Hyaluronic acid
description: Platelet rich plasma (PRP) and Hyaluronic acid (HA) are beneficial for patients with osteoarthritis of knee.
arm group label: Platelet rich plasma + Hyaluronic acid
intervention type: Drug
intervention name: platelet rich plasma + normal saline
description: The normal salin as the placebo intervention was injection control group.
arm group label: Platelet rich plasma + normal saline
criteria: 
gender: All
minimum age: 50 Years
maximum age: 75 Years
healthy volunteers: No
last name: Yung-Tsan Wu, MD
role: Principal Investigator
affiliation: Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, National Defense Medical Center
facility: 
country: Taiwan
citation: Abate M, Verna S, Schiavone C, Di Gregorio P, Salini V. Efficacy and safety profile of a compound composed of platelet-rich plasma and hyaluronic acid in the treatment for knee osteoarthritis (preliminary results). Eur J Orthop Surg Traumatol. 2015 Dec;25(8):1321-6. doi: 10.1007/s00590-015-1693-3. Epub 2015 Sep 24.
PMID: 26403468
citation: Lana JF, Weglein A, Sampson SE, Vicente EF, Huber SC, Souza CV, Ambach MA, Vincent H, Urban-Paffaro A, Onodera CM, Annichino-Bizzacchi JM, Santana MH, Belangero WD. Randomized controlled trial comparing hyaluronic acid, platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee. J Stem Cells Regen Med. 2016 Nov 29;12(2):69-78. doi: 10.46582/jsrm.1202011. eCollection 2016.
PMID: 28096631
citation: Chen SH, Kuan TS, Kao MJ, Wu WT, Chou LW. Clinical effectiveness in severe knee osteoarthritis after intra-articular platelet-rich plasma therapy in association with hyaluronic acid injection: three case reports. Clin Interv Aging. 2016 Sep 8;11:1213-1219. doi: 10.2147/CIA.S114795. eCollection 2016.
PMID: 27660427
citation: Dallari D, Stagni C, Rani N, Sabbioni G, Pelotti P, Torricelli P, Tschon M, Giavaresi G. Ultrasound-Guided Injection of Platelet-Rich Plasma and Hyaluronic Acid, Separately and in Combination, for Hip Osteoarthritis: A Randomized Controlled Study. Am J Sports Med. 2016 Mar;44(3):664-71. doi: 10.1177/0363546515620383. Epub 2016 Jan 21.
PMID: 26797697
responsible party type: Principal Investigator
investigator affiliation: Tri-Service General Hospital
investigator full name: Yung-Tsan Wu
investigator title: Attending Physician
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
mesh term: Hyaluronic Acid