<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/NCT03783455</url>
  </required_header>
  <id_info>
    <org_study_id>NAJL</org_study_id>
    <nct_id>NCT03783455</nct_id>
  </id_info>
  <brief_title>Effectiveness of Five Intraarticular Strategies on Knee Osteoarthritis</brief_title>
  <official_title>Assessment of Short-term Effectiveness of Five Local Treatment Modalities in Patients With Symptomatic Knee Osteoarthritis: a Randomized Prospective Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maimónides Biomedical Research Institute of Córdoba</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maimónides Biomedical Research Institute of Córdoba</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      BACKGROUND: Current medical treatment strategies for knee osteoarthritis (OA) are aimed at&#xD;
      pain reduction and symptom control. The Non-Arthroscopic Joint Lavage (NAJL) is included&#xD;
      inside the therapeutic algorithm of knee OA when other therapies are contraindicated or have&#xD;
      lost effectiveness. The large variety of potentially invasive interventions available (joint&#xD;
      lavage included) has raised the need to assess their efficacy. The objective of this study is&#xD;
      to compare the short-term effectiveness of five treatment strategies in patients with knee&#xD;
      osteoarthritis (OA).&#xD;
&#xD;
      METHODS: It was conducted a randomized prospective study involving 150 patients of whom 76.7%&#xD;
      were females. The age range was 40-81 years. All patients had knee OA according to the&#xD;
      American College of Rheumatology criteria, with Kellgren-Lawrence radiographic grades II and&#xD;
      III. Patients were assigned to five groups, 1) non-arthroscopic joint lavage (NAJL) (n= 30),&#xD;
      2) NAJL plus hyaluronic acid (HA) (n= 32), 3) NAJL plus corticosteroid (CS) (n= 32), 4) HA&#xD;
      (n= 31), 5) CS (n= 25). Evaluations took place at baseline, one and three months after&#xD;
      enrollment. Demographic variables, Western Ontario and McMaster University Osteoarthritis&#xD;
      Index (WOMAC) and Lequesne scores were recorded. Statistical analysis included mixed analysis&#xD;
      of variance, post-hoc comparisons with Sidak's adjustment, and multiple linear regression&#xD;
      using as outcome WOMAC total at 3 months.&#xD;
&#xD;
      TRIAL REGISTRATION: The protocol of the study was approved by the &quot;Hospital Universitario&#xD;
      Reina Sofía&quot; Ethics Committee, under the number 1996, in the Minutes 208 of 29 May 2012.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2015</start_date>
  <completion_date type="Actual">June 1, 2016</completion_date>
  <primary_completion_date type="Actual">June 1, 2016</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>
    <intervention_model_description>Open, controlled, randomized and prospective study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>WOMAC 3.1 Index total</measure>
    <time_frame>WOMAC total at 3 months</time_frame>
    <description>The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Lequesne Index</measure>
    <time_frame>baseline, at one month and at three months</time_frame>
    <description>Lequesne Index is a ten question questionnaire that asseses pain and function in patients with osteoarthritis of the knee. It is composed by five questions about pain, being three of them from 0 to 2, and two of them from 0 to 1 point, two questions about maximum distance walked (from 0 to 6 points one and from 0 to 2 the second) and four questions about activities of daily living (from 0 to 2). The total values is the sum of all questions points and range from 1 to 24, being 1-4 mild handicap, 5-7 moderate, 8-10 severe, 11-13 very severe, and &gt;14 extremely severe handicap.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC 3.1 Index pain</measure>
    <time_frame>WOMAC pain at baseline</time_frame>
    <description>The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC 3.1 Index pain</measure>
    <time_frame>WOMAC pain at one month</time_frame>
    <description>The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC 3.1 Index pain</measure>
    <time_frame>WOMAC pain at three months</time_frame>
    <description>The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC 3.1 Index function</measure>
    <time_frame>WOMAC function at baseline</time_frame>
    <description>The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC 3.1 Index function</measure>
    <time_frame>WOMAC function at one month</time_frame>
    <description>The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC 3.1 Index function</measure>
    <time_frame>WOMAC function at three months</time_frame>
    <description>The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC 3.1 Index stiffness</measure>
    <time_frame>WOMAC stiffness at baseline</time_frame>
    <description>The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC 3.1 Index stiffness</measure>
    <time_frame>WOMAC stiffness at one month</time_frame>
    <description>The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC 3.1 Index stiffness</measure>
    <time_frame>WOMAC stiffness at three months</time_frame>
    <description>The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC 3.1 Index total</measure>
    <time_frame>WOMAC total at baseline</time_frame>
    <description>The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC 3.1 Index total</measure>
    <time_frame>WOMAC total at one month</time_frame>
    <description>The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Osteo Arthritis Knee</condition>
  <arm_group>
    <arm_group_label>Non arthroscopic joint lavage (NAJL)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution, followed by an injection of local anesthetic (5 mL of 2% mepivacaine hydrochloride) into the outer mediopatellar zone. The anesthetic was allowed to act, and an access way was then opened with a No. 16 abocat. Any effusion in the joint was drained. Then, approximately 100 mL of cold saline was instilled through the outer access way. Once the knee was distended, a further 5 mL of local anesthetic was injected into the inner mediopatellar zone, and a new abocat guide was used to establish the inner drainage way. The lavage proper involved instillation of 4 L of cold (8ºC) saline at a constant flow-rate using a dropper line connected to the entry way; the inner zone was also connected to another, free-fall dropper.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non arthroscopic joint lavage plus corticosteroid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution, followed by an injection of local anesthetic (5 mL of 2% mepivacaine hydrochloride) into the outer mediopatellar zone. The anesthetic was allowed to act, and an access way was then opened with a No. 16 abocat. Any effusion in the joint was drained. Then, approximately 100 mL of cold saline was instilled through the outer access way. Once the knee was distended, a further 5 mL of local anesthetic was injected into the inner mediopatellar zone, and a new abocat guide was used to establish the inner drainage way. The lavage proper involved instillation of 4 L of cold (8ºC) saline at a constant flow-rate using a dropper line connected to the entry way; the inner zone was also connected to another, free-fall dropper. Following administration of the joint lavage, the NAJL plus corticosteroid group was given an intra-articular injection containing 40 mg of triamcinolone acetonide.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non arthroscopic joint lavage plus hyaluronic acid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution, followed by an injection of local anesthetic (5 mL of 2% mepivacaine hydrochloride) into the outer mediopatellar zone. The anesthetic was allowed to act, and an access way was then opened with a No. 16 abocat. Any effusion in the joint was drained. Then, approximately 100 mL of cold saline was instilled through the outer access way. Once the knee was distended, a further 5 mL of local anesthetic was injected into the inner mediopatellar zone, and a new abocat guide was used to establish the inner drainage way. The lavage proper involved instillation of 4 L of cold (8ºC) saline at a constant flow-rate using a dropper line connected to the entry way; the inner zone was also connected to another, free-fall dropper. Following administration of the joint lavage, the patients were given an intra-articular injection containing 4 ml of a bioengineered hyaluronic acid.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intraarticular injection of hyaluronic acid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution. This was followed by an intraarticular injection containing 4 mL of a bioengineered hyaluronic acid.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intraarticular injection of corticosteroid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution. This was followed by an intraarticular injection containing 40 mg of triamcinolone acetonide.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Non arthroscopic joint lavage</intervention_name>
    <description>Instillation of 4 litters of cold physiological serum</description>
    <arm_group_label>Non arthroscopic joint lavage (NAJL)</arm_group_label>
    <other_name>NAJL</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Non arthroscopic joint lavage plus corticosteroid</intervention_name>
    <description>Instillation of 4 litters of cold physiological serum followed by intraarticular injection of triamcinolone</description>
    <arm_group_label>Non arthroscopic joint lavage plus corticosteroid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Non arthroscopic joint lavage plus hyaluronic acid</intervention_name>
    <description>Instillation of 4 litters of cold physiological serum followed by intraarticular injection of hyaluronic acid</description>
    <arm_group_label>Non arthroscopic joint lavage plus hyaluronic acid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Intraarticular injection of corticosteroid</intervention_name>
    <description>Intraarticular injection containing 40 mg of triamcinolone acetonide.</description>
    <arm_group_label>Intraarticular injection of corticosteroid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Intraarticular injection of hyaluronic acid</intervention_name>
    <description>Intraarticular injection containing 4 mL of a bioengineered hyaluronic acid.</description>
    <arm_group_label>Intraarticular injection of hyaluronic acid</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Meeting American College of Rheumatology (ACR) criteria for knee OA, symptoms for at&#xD;
             least three months despite conservative medical treatment, knee OA grade II or III on&#xD;
             the radiological Kellgren-Lawrence scale, and voluntary collaboration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ankylosis of joint;&#xD;
&#xD;
          -  total arthroplasty or previous osteotomy&#xD;
&#xD;
          -  infected injury;&#xD;
&#xD;
          -  treatment with dicumarinic drugs or alterations in blood coagulation,&#xD;
&#xD;
          -  venous insufficiency or episode of venous thrombosis;&#xD;
&#xD;
          -  administration of hyaluronic acid (HA) in the previous year, and/or corticosteroid&#xD;
             (CS) infiltration or NAJL in the previous three months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lourdes Ladehesa, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario Reina Sofía</affiliation>
  </overall_official>
  <reference>
    <citation>Cope PJ, Ourradi K, Li Y, Sharif M. Models of osteoarthritis: the good, the bad and the promising. Osteoarthritis Cartilage. 2019 Feb;27(2):230-239. doi: 10.1016/j.joca.2018.09.016. Epub 2018 Oct 25.</citation>
    <PMID>30391394</PMID>
  </reference>
  <reference>
    <citation>Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, Towheed T, Welch V, Wells G, Tugwell P; American College of Rheumatology. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012 Apr;64(4):465-74. doi: 10.1002/acr.21596.</citation>
    <PMID>22563589</PMID>
  </reference>
  <reference>
    <citation>Cooper C, Rannou F, Richette P, Bruyere O, Al-Daghri N, Altman RD, Brandi ML, Collaud Basset S, Herrero-Beaumont G, Migliore A, Pavelka K, Uebelhart D, Reginster JY. Use of Intraarticular Hyaluronic Acid in the Management of Knee Osteoarthritis in Clinical Practice. Arthritis Care Res (Hoboken). 2017 Sep;69(9):1287-1296. doi: 10.1002/acr.23204. Epub 2017 Aug 8. No abstract available.</citation>
    <PMID>28118523</PMID>
  </reference>
  <reference>
    <citation>Escobar A, Quintana JM, Bilbao A, Azkarate J, Guenaga JI. Validation of the Spanish version of the WOMAC questionnaire for patients with hip or knee osteoarthritis. Western Ontario and McMaster Universities Osteoarthritis Index. Clin Rheumatol. 2002 Nov;21(6):466-71. doi: 10.1007/s100670200117.</citation>
    <PMID>12447629</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>December 18, 2018</last_update_submitted>
  <last_update_submitted_qc>December 18, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Corticosteroid</keyword>
  <keyword>Hyaluronic acid</keyword>
  <keyword>Joint Lavage</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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03783455
org study id: NAJL
nct id: NCT03783455
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
BACKGROUND: Current medical treatment strategies for knee osteoarthritis (OA) are aimed at
      pain reduction and symptom control. The Non-Arthroscopic Joint Lavage (NAJL) is included
      inside the therapeutic algorithm of knee OA when other therapies are contraindicated or have
      lost effectiveness. The large variety of potentially invasive interventions available (joint
      lavage included) has raised the need to assess their efficacy. The objective of this study is
      to compare the short-term effectiveness of five treatment strategies in patients with knee
      osteoarthritis (OA).

      METHODS: It was conducted a randomized prospective study involving 150 patients of whom 76.7%
      were females. The age range was 40-81 years. All patients had knee OA according to the
      American College of Rheumatology criteria, with Kellgren-Lawrence radiographic grades II and
      III. Patients were assigned to five groups, 1) non-arthroscopic joint lavage (NAJL) (n= 30),
      2) NAJL plus hyaluronic acid (HA) (n= 32), 3) NAJL plus corticosteroid (CS) (n= 32), 4) HA
      (n= 31), 5) CS (n= 25). Evaluations took place at baseline, one and three months after
      enrollment. Demographic variables, Western Ontario and McMaster University Osteoarthritis
      Index (WOMAC) and Lequesne scores were recorded. Statistical analysis included mixed analysis
      of variance, post-hoc comparisons with Sidak's adjustment, and multiple linear regression
      using as outcome WOMAC total at 3 months.

      TRIAL REGISTRATION: The protocol of the study was approved by the "Hospital Universitario
      Reina Sofía" Ethics Committee, under the number 1996, in the Minutes 208 of 29 May 2012.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Open, controlled, randomized and prospective study.
primary purpose: Treatment
masking: None (Open Label)
measure: WOMAC 3.1 Index total
time frame: WOMAC total at 3 months
description: The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.
measure: Lequesne Index
time frame: baseline, at one month and at three months
description: Lequesne Index is a ten question questionnaire that asseses pain and function in patients with osteoarthritis of the knee. It is composed by five questions about pain, being three of them from 0 to 2, and two of them from 0 to 1 point, two questions about maximum distance walked (from 0 to 6 points one and from 0 to 2 the second) and four questions about activities of daily living (from 0 to 2). The total values is the sum of all questions points and range from 1 to 24, being 1-4 mild handicap, 5-7 moderate, 8-10 severe, 11-13 very severe, and >14 extremely severe handicap.
measure: WOMAC 3.1 Index pain
time frame: WOMAC pain at baseline
description: The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.
measure: WOMAC 3.1 Index pain
time frame: WOMAC pain at one month
description: The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.
measure: WOMAC 3.1 Index pain
time frame: WOMAC pain at three months
description: The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.
measure: WOMAC 3.1 Index function
time frame: WOMAC function at baseline
description: The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.
measure: WOMAC 3.1 Index function
time frame: WOMAC function at one month
description: The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.
measure: WOMAC 3.1 Index function
time frame: WOMAC function at three months
description: The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.
measure: WOMAC 3.1 Index stiffness
time frame: WOMAC stiffness at baseline
description: The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.
measure: WOMAC 3.1 Index stiffness
time frame: WOMAC stiffness at one month
description: The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.
measure: WOMAC 3.1 Index stiffness
time frame: WOMAC stiffness at three months
description: The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.
measure: WOMAC 3.1 Index total
time frame: WOMAC total at baseline
description: The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.
measure: WOMAC 3.1 Index total
time frame: WOMAC total at one month
description: The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.
arm group label: Non arthroscopic joint lavage (NAJL)
arm group type: Active Comparator
description: Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution, followed by an injection of local anesthetic (5 mL of 2% mepivacaine hydrochloride) into the outer mediopatellar zone. The anesthetic was allowed to act, and an access way was then opened with a No. 16 abocat. Any effusion in the joint was drained. Then, approximately 100 mL of cold saline was instilled through the outer access way. Once the knee was distended, a further 5 mL of local anesthetic was injected into the inner mediopatellar zone, and a new abocat guide was used to establish the inner drainage way. The lavage proper involved instillation of 4 L of cold (8ºC) saline at a constant flow-rate using a dropper line connected to the entry way; the inner zone was also connected to another, free-fall dropper.
arm group label: Non arthroscopic joint lavage plus corticosteroid
arm group type: Active Comparator
description: Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution, followed by an injection of local anesthetic (5 mL of 2% mepivacaine hydrochloride) into the outer mediopatellar zone. The anesthetic was allowed to act, and an access way was then opened with a No. 16 abocat. Any effusion in the joint was drained. Then, approximately 100 mL of cold saline was instilled through the outer access way. Once the knee was distended, a further 5 mL of local anesthetic was injected into the inner mediopatellar zone, and a new abocat guide was used to establish the inner drainage way. The lavage proper involved instillation of 4 L of cold (8ºC) saline at a constant flow-rate using a dropper line connected to the entry way; the inner zone was also connected to another, free-fall dropper. Following administration of the joint lavage, the NAJL plus corticosteroid group was given an intra-articular injection containing 40 mg of triamcinolone acetonide.
arm group label: Non arthroscopic joint lavage plus hyaluronic acid
arm group type: Active Comparator
description: Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution, followed by an injection of local anesthetic (5 mL of 2% mepivacaine hydrochloride) into the outer mediopatellar zone. The anesthetic was allowed to act, and an access way was then opened with a No. 16 abocat. Any effusion in the joint was drained. Then, approximately 100 mL of cold saline was instilled through the outer access way. Once the knee was distended, a further 5 mL of local anesthetic was injected into the inner mediopatellar zone, and a new abocat guide was used to establish the inner drainage way. The lavage proper involved instillation of 4 L of cold (8ºC) saline at a constant flow-rate using a dropper line connected to the entry way; the inner zone was also connected to another, free-fall dropper. Following administration of the joint lavage, the patients were given an intra-articular injection containing 4 ml of a bioengineered hyaluronic acid.
arm group label: Intraarticular injection of hyaluronic acid
arm group type: Active Comparator
description: Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution. This was followed by an intraarticular injection containing 4 mL of a bioengineered hyaluronic acid.
arm group label: Intraarticular injection of corticosteroid
arm group type: Active Comparator
description: Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution. This was followed by an intraarticular injection containing 40 mg of triamcinolone acetonide.
intervention type: Procedure
intervention name: Non arthroscopic joint lavage
description: Instillation of 4 litters of cold physiological serum
arm group label: Non arthroscopic joint lavage (NAJL)
other name: NAJL
intervention type: Procedure
intervention name: Non arthroscopic joint lavage plus corticosteroid
description: Instillation of 4 litters of cold physiological serum followed by intraarticular injection of triamcinolone
arm group label: Non arthroscopic joint lavage plus corticosteroid
intervention type: Procedure
intervention name: Non arthroscopic joint lavage plus hyaluronic acid
description: Instillation of 4 litters of cold physiological serum followed by intraarticular injection of hyaluronic acid
arm group label: Non arthroscopic joint lavage plus hyaluronic acid
intervention type: Procedure
intervention name: Intraarticular injection of corticosteroid
description: Intraarticular injection containing 40 mg of triamcinolone acetonide.
arm group label: Intraarticular injection of corticosteroid
intervention type: Procedure
intervention name: Intraarticular injection of hyaluronic acid
description: Intraarticular injection containing 4 mL of a bioengineered hyaluronic acid.
arm group label: Intraarticular injection of hyaluronic acid
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Lourdes Ladehesa, MD
role: Principal Investigator
affiliation: Hospital Universitario Reina Sofía
citation: Cope PJ, Ourradi K, Li Y, Sharif M. Models of osteoarthritis: the good, the bad and the promising. Osteoarthritis Cartilage. 2019 Feb;27(2):230-239. doi: 10.1016/j.joca.2018.09.016. Epub 2018 Oct 25.
PMID: 30391394
citation: Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, Towheed T, Welch V, Wells G, Tugwell P; American College of Rheumatology. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012 Apr;64(4):465-74. doi: 10.1002/acr.21596.
PMID: 22563589
citation: Cooper C, Rannou F, Richette P, Bruyere O, Al-Daghri N, Altman RD, Brandi ML, Collaud Basset S, Herrero-Beaumont G, Migliore A, Pavelka K, Uebelhart D, Reginster JY. Use of Intraarticular Hyaluronic Acid in the Management of Knee Osteoarthritis in Clinical Practice. Arthritis Care Res (Hoboken). 2017 Sep;69(9):1287-1296. doi: 10.1002/acr.23204. Epub 2017 Aug 8. No abstract available.
PMID: 28118523
citation: Escobar A, Quintana JM, Bilbao A, Azkarate J, Guenaga JI. Validation of the Spanish version of the WOMAC questionnaire for patients with hip or knee osteoarthritis. Western Ontario and McMaster Universities Osteoarthritis Index. Clin Rheumatol. 2002 Nov;21(6):466-71. doi: 10.1007/s100670200117.
PMID: 12447629
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
mesh term: Hyaluronic Acid
sharing ipd: No