<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/NCT03758755</url>
  </required_header>
  <id_info>
    <org_study_id>18-3150</org_study_id>
    <nct_id>NCT03758755</nct_id>
  </id_info>
  <brief_title>Blood Flow Restriction Following ACL Reconstruction</brief_title>
  <acronym>BFR</acronym>
  <official_title>The Effect of Blood Flow Restriction Therapy Following Anterior Cruciate Ligament Reconstruction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Inova Health Care Services</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Inova Health Care Services</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main objective is to determine the impact of Blood Flow Restriction (BFR) therapy, in&#xD;
      comparison to a standard rehabilitation protocol, on preventing atrophy, improving quadriceps&#xD;
      strength and improving functional outcomes of patients recovering from ACL reconstruction.&#xD;
      The investigators hypothesize that patients undergoing BFR therapy after ACL reconstruction&#xD;
      surgery will have better functional outcomes than those undergoing normal rehabilitation&#xD;
      without BFR therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recovery from anterior cruciate ligament (ACL) reconstruction involves early physical therapy&#xD;
      to promote muscular development. Traditional training regimens are based on the concept that&#xD;
      muscle growth is induced with high resistance exercises of at least 65-70% of 1-repetition&#xD;
      maximum. Achieving a high resistance level can be challenging in the early post-surgical&#xD;
      patient who may be limited by pain, muscle atrophy, diminished proprioception, and&#xD;
      psychological factors. Increasing evidence has suggested that Blood Flow Restriction (BFR) in&#xD;
      resistance training, while transmitting a decreased load (25-50% of 1-repetition maximum)&#xD;
      across the surgical site, may provide an additional benefit of inducing muscular development&#xD;
      similar to that of high intensity exercises .&#xD;
&#xD;
      Augmenting exercises with BFR involves an external pressure cuff applied to the proximal&#xD;
      portion of the extremity, which is inflated to a pressure that restricts venous outflow while&#xD;
      allowing arterial inflow to continue. This creates a physiologic environment for the patient&#xD;
      to gain the hypertrophic effect of high resistance training, though at a lower and safer&#xD;
      intensity. Studies suggest that BFR stimulates muscular development through an increase in&#xD;
      metabolic stress, muscle fiber recruitment, cell swelling, and protein synthesis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2018</start_date>
  <completion_date type="Actual">October 26, 2022</completion_date>
  <primary_completion_date type="Actual">November 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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>International Knee Documentation Committee (IKDC) Questionnaire Score</measure>
    <time_frame>Measured preoperatively and at 12 weeks post-op.</time_frame>
    <description>The International Knee Documentation Committee (IKDC Questionnaire) is a knee-specific patient-reported outcome measure. The IKDC Questionnaire is a subjective scale that provides patients with an overall function score. The questionnaire looks at 3 categories: symptoms, sports activity, and knee function. Scores are obtained by summing the individual items, then transforming the crude total to a scaled number that ranges from 0 to 100. This final number is interpreted as a measure of function with higher scores representing higher levels of function.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Visual Analog Score</measure>
    <time_frame>Measured preoperatively, at 2-weeks post-op, 6 weeks post-op, and 12 weeks post-op</time_frame>
    <description>The visual analog scale (VAS) is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between &quot;no pain&quot; and &quot;worst pain,&quot; with &quot;no pain&quot; corresponding to a VAS score of 0 and &quot;worst pain&quot; corresponding to a VAS score of 10.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quadriceps Tendon Strength</measure>
    <time_frame>Tracked from initiation of therapy 2 weeks post-op through 12 weeks post-op.</time_frame>
    <description>We will measure quadriceps tendon strength (closed chain) strength using a hand-held dynamometer placed just distal to the knee joint on the posterior calf with the patient in the supine position. The outcome will be reported biweekly as a percentage of the strength of the contralateral side, and then finally reported as a change in strength from the first measurement to the final measurement. The results reported in this data table refer to the percent strength of the operated leg when compared to the contralateral side. The change in strength results can be found in the statistical analysis section.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Thigh Circumference</measure>
    <time_frame>Tracked in the perioperative week and then from initiation of therapy 2 weeks post-op through 12 weeks post-op.</time_frame>
    <description>A tape measure will be used to measure the thigh circumference 15 cm proximal to the superior pole of the patella. The outcome will be reported biweekly as a percentage of the contralateral side, and then finally reported as a change in circumference from the first measurement to the final measurement. The results reported in this data table refer to the percent circumference of the operated leg when compared to the contralateral side. The change in circumference results can be found in the statistical analysis section.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Degrees of Knee Flexion</measure>
    <time_frame>Tracked in the perioperative week and then from initiation of therapy 2 weeks post-op through 12 weeks post-op.</time_frame>
    <description>Degrees of knee flexion will be measured on the operative side by a licensed physical therapist. The outcome will be reported biweekly and then finally reported as a change in degrees from the first measurement to the final measurement. The results reported in this data table refer to the degrees of knee flexion at each reported time point. The change in knee flexion results can be found in the statistical analysis section.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Degrees of Knee Extension</measure>
    <time_frame>Tracked in the perioperative week and then from initiation of therapy 2 weeks post-op through 12 weeks post-op.</time_frame>
    <description>Degrees of knee extension will be measured on the operative side by a licensed physical therapist, with zero degrees indicating the knee completely at extension and negative degrees indicating degrees of hyperextension. The outcome will be reported biweekly and then finally reported as a change in degrees from the first measurement to the final measurement. The results reported in this data table refer to the degrees of knee extension at each reported time point. The change in knee extension results can be found in the statistical analysis section.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Effects</measure>
    <time_frame>Tracked from initiation of therapy 2 weeks post-op through 12 weeks post-op</time_frame>
    <description>Observation of any adverse events associated with BFR therapy, such as numbness, cuff-site pain, and bruising.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">49</enrollment>
  <condition>Anterior Cruciate Ligament Rupture</condition>
  <arm_group>
    <arm_group_label>BFR Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group will undergo physical therapy exercises per the standard of care, with the addition of Blood Flow Restriction (BFR) utilizing a wide pressure cuff. BFR exercises will be initiated two weeks post-op, and continued for 16 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No BFR</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>This group of patients will undergo physical therapy exercises per the current standard of care after their ACL reconstruction without BFR</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Blood Flow Restriction Therapy</intervention_name>
    <description>A wide pressure cuff will be applied to the upper thigh prior to starting strengthening exercises. The cuff is inflated to 80% of resting systolic blood pressure. The cuff remains inflated for the entirety of the exercise (4 sets of a specific movement). Once the exercises are completed, it is deflated for a minimum of one minute before the next type of exercises are started.</description>
    <arm_group_label>BFR Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>ACL Reconstruction rehabilitation</intervention_name>
    <description>post-operative rehabilitation according to current standards of care</description>
    <arm_group_label>BFR Therapy</arm_group_label>
    <arm_group_label>No BFR</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 13-35 years at the time of surgery&#xD;
&#xD;
          2. Anterior Cruciate Ligament (ACL) reconstruction&#xD;
&#xD;
          3. Using a physical therapy center with Blood Flow Restriction capabilities.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Concomitant ligament reconstruction&#xD;
&#xD;
          2. Concurrent procedures that require delayed weight bearing (ie: High Tibial Osteotomy&#xD;
             (HTO), multi-ligament reconstruction, microfracture, etc)&#xD;
&#xD;
          3. History of Deep Vein Thrombosis (DVT)/Pulmonary Embolism (PE)&#xD;
&#xD;
          4. Immunocompromising conditions (ie: Rheumatoid arthritis, chronic steroid use, etc.)&#xD;
&#xD;
          5. History of coagulation disorders or current use of anticoagulants&#xD;
&#xD;
          6. Completion of physical therapy at a location not affiliated with the study&#xD;
&#xD;
          7. Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Edward Chang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Orthopedic Surgeon</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Inova Health System</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Hughes L, Paton B, Rosenblatt B, Gissane C, Patterson SD. Blood flow restriction training in clinical musculoskeletal rehabilitation: a systematic review and meta-analysis. Br J Sports Med. 2017 Jul;51(13):1003-1011. doi: 10.1136/bjsports-2016-097071. Epub 2017 Mar 4.</citation>
    <PMID>28259850</PMID>
  </reference>
  <reference>
    <citation>Iversen E, Rostad V, Larmo A. Intermittent blood flow restriction does not reduce atrophy following anterior cruciate ligament reconstruction. J Sport Health Sci. 2016 Mar;5(1):115-118. doi: 10.1016/j.jshs.2014.12.005. Epub 2015 Apr 18.</citation>
    <PMID>30356481</PMID>
  </reference>
  <reference>
    <citation>Ohta H, Kurosawa H, Ikeda H, Iwase Y, Satou N, Nakamura S. Low-load resistance muscular training with moderate restriction of blood flow after anterior cruciate ligament reconstruction. Acta Orthop Scand. 2003 Feb;74(1):62-8. doi: 10.1080/00016470310013680.</citation>
    <PMID>12635796</PMID>
  </reference>
  <reference>
    <citation>Scott BR, Loenneke JP, Slattery KM, Dascombe BJ. Blood flow restricted exercise for athletes: A review of available evidence. J Sci Med Sport. 2016 May;19(5):360-7. doi: 10.1016/j.jsams.2015.04.014. Epub 2015 May 9.</citation>
    <PMID>26118847</PMID>
  </reference>
  <reference>
    <citation>Suga T, Okita K, Takada S, Omokawa M, Kadoguchi T, Yokota T, Hirabayashi K, Takahashi M, Morita N, Horiuchi M, Kinugawa S, Tsutsui H. Effect of multiple set on intramuscular metabolic stress during low-intensity resistance exercise with blood flow restriction. Eur J Appl Physiol. 2012 Nov;112(11):3915-20. doi: 10.1007/s00421-012-2377-x. Epub 2012 Mar 14.</citation>
    <PMID>22415101</PMID>
  </reference>
  <reference>
    <citation>Takada S, Okita K, Suga T, Omokawa M, Morita N, Horiuchi M, Kadoguchi T, Takahashi M, Hirabayashi K, Yokota T, Kinugawa S, Tsutsui H. Blood flow restriction exercise in sprinters and endurance runners. Med Sci Sports Exerc. 2012 Mar;44(3):413-9. doi: 10.1249/MSS.0b013e31822f39b3.</citation>
    <PMID>21795999</PMID>
  </reference>
  <reference>
    <citation>Takarada Y, Takazawa H, Sato Y, Takebayashi S, Tanaka Y, Ishii N. Effects of resistance exercise combined with moderate vascular occlusion on muscular function in humans. J Appl Physiol (1985). 2000 Jun;88(6):2097-106. doi: 10.1152/jappl.2000.88.6.2097.</citation>
    <PMID>10846023</PMID>
  </reference>
  <reference>
    <citation>Yasuda T, Brechue WF, Fujita T, Shirakawa J, Sato Y, Abe T. Muscle activation during low-intensity muscle contractions with restricted blood flow. J Sports Sci. 2009 Mar;27(5):479-89. doi: 10.1080/02640410802626567.</citation>
    <PMID>19253083</PMID>
  </reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>November 14, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <results_first_submitted>October 26, 2022</results_first_submitted>
  <results_first_submitted_qc>November 30, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">December 22, 2022</results_first_posted>
  <last_update_submitted>November 30, 2022</last_update_submitted>
  <last_update_submitted_qc>November 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Inova Health Care Services</investigator_affiliation>
    <investigator_full_name>Edward Chang, MD</investigator_full_name>
    <investigator_title>Orthopedic Surgeon</investigator_title>
  </responsible_party>
  <keyword>BFR</keyword>
  <keyword>ACL</keyword>
  <keyword>rehabilitation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rupture</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 13, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT03758755/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Patients were enrolled from two fellowship trained sports medicine orthopedic surgeons at a large health system from November 2018 to November 2021.</recruitment_details>
      <pre_assignment_details>Of 49 enrolled patients, 45 met inclusion/exclusion criteria and were randomized to treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>BFR Therapy</title>
          <description>This group will undergo physical therapy exercises per the standard of care, with the addition of Blood Flow Restriction (BFR) utilizing a wide pressure cuff. BFR exercises will be initiated two weeks post-op, and continued for 16 weeks.&#xD;
Blood Flow Restriction Therapy: A wide pressure cuff will be applied to the upper thigh prior to starting strengthening exercises. The cuff is inflated to 80% of resting systolic blood pressure. The cuff remains inflated for the entirety of the exercise (4 sets of a specific movement). Once the exercises are completed, it is deflated for a minimum of one minute before the next type of exercises are started.&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
        </group>
        <group group_id="P2">
          <title>No BFR</title>
          <description>This group of patients will undergo physical therapy exercises per the current standard of care after their ACL reconstruction without BFR&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>BFR Therapy</title>
          <description>This group will undergo physical therapy exercises per the standard of care, with the addition of Blood Flow Restriction (BFR) utilizing a wide pressure cuff. BFR exercises will be initiated two weeks post-op, and continued for 16 weeks.&#xD;
Blood Flow Restriction Therapy: A wide pressure cuff will be applied to the upper thigh prior to starting strengthening exercises. The cuff is inflated to 80% of resting systolic blood pressure. The cuff remains inflated for the entirety of the exercise (4 sets of a specific movement). Once the exercises are completed, it is deflated for a minimum of one minute before the next type of exercises are started.&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
        </group>
        <group group_id="B2">
          <title>No BFR</title>
          <description>This group of patients will undergo physical therapy exercises per the current standard of care after their ACL reconstruction without BFR&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
            <count group_id="B2" value="20"/>
            <count group_id="B3" value="45"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="20"/>
                    <count group_id="B3" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25.4" spread="10.08"/>
                    <measurement group_id="B2" value="29.0" spread="9.41"/>
                    <measurement group_id="B3" value="26.8" spread="9.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="20"/>
                    <count group_id="B3" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Laterality</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="20"/>
                    <count group_id="B3" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Right</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Left</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Type of Anterior Cruciate Ligament (ACL) Graft</title>
          <description>Graft choices for ACL Reconstruction varied based on surgeon and patient preference, and consisted of Allograft, Bone-Patellar Tendon-Bone Autograft, Hamstring Tendon Autograft, and Quadriceps Tendon Autograft.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="20"/>
                    <count group_id="B3" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Allograft</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Bone-Patellar Tendon-Bone Autograft</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hamstring Tendon Autograft</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Quadriceps Tendon Autograft</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>International Knee Documentation Committee (IKDC) Questionnaire Score</title>
        <description>The International Knee Documentation Committee (IKDC Questionnaire) is a knee-specific patient-reported outcome measure. The IKDC Questionnaire is a subjective scale that provides patients with an overall function score. The questionnaire looks at 3 categories: symptoms, sports activity, and knee function. Scores are obtained by summing the individual items, then transforming the crude total to a scaled number that ranges from 0 to 100. This final number is interpreted as a measure of function with higher scores representing higher levels of function.</description>
        <time_frame>Measured preoperatively and at 12 weeks post-op.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BFR Therapy</title>
            <description>This group will undergo physical therapy exercises per the standard of care, with the addition of Blood Flow Restriction (BFR) utilizing a wide pressure cuff. BFR exercises will be initiated two weeks post-op, and continued for 16 weeks.&#xD;
Blood Flow Restriction Therapy: A wide pressure cuff will be applied to the upper thigh prior to starting strengthening exercises. The cuff is inflated to 80% of resting systolic blood pressure. The cuff remains inflated for the entirety of the exercise (4 sets of a specific movement). Once the exercises are completed, it is deflated for a minimum of one minute before the next type of exercises are started.&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
          <group group_id="O2">
            <title>No BFR</title>
            <description>This group of patients will undergo physical therapy exercises per the current standard of care after their ACL reconstruction without BFR&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
        </group_list>
        <measure>
          <title>International Knee Documentation Committee (IKDC) Questionnaire Score</title>
          <description>The International Knee Documentation Committee (IKDC Questionnaire) is a knee-specific patient-reported outcome measure. The IKDC Questionnaire is a subjective scale that provides patients with an overall function score. The questionnaire looks at 3 categories: symptoms, sports activity, and knee function. Scores are obtained by summing the individual items, then transforming the crude total to a scaled number that ranges from 0 to 100. This final number is interpreted as a measure of function with higher scores representing higher levels of function.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Preoperative visit</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.40" spread="8.00"/>
                    <measurement group_id="O2" value="50.80" spread="4.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.83" spread="2.93"/>
                    <measurement group_id="O2" value="52.86" spread="3.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis: there is no difference between groups in IKDC score at 12 weeks post-op.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The a priori threshold for statistical significance was set at 0.05.</non_inferiority_desc>
            <p_value>0.0219</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Visual Analog Score</title>
        <description>The visual analog scale (VAS) is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between &quot;no pain&quot; and &quot;worst pain,&quot; with &quot;no pain&quot; corresponding to a VAS score of 0 and &quot;worst pain&quot; corresponding to a VAS score of 10.</description>
        <time_frame>Measured preoperatively, at 2-weeks post-op, 6 weeks post-op, and 12 weeks post-op</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BFR Therapy</title>
            <description>This group will undergo physical therapy exercises per the standard of care, with the addition of Blood Flow Restriction (BFR) utilizing a wide pressure cuff. BFR exercises will be initiated two weeks post-op, and continued for 16 weeks.&#xD;
Blood Flow Restriction Therapy: A wide pressure cuff will be applied to the upper thigh prior to starting strengthening exercises. The cuff is inflated to 80% of resting systolic blood pressure. The cuff remains inflated for the entirety of the exercise (4 sets of a specific movement). Once the exercises are completed, it is deflated for a minimum of one minute before the next type of exercises are started.&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
          <group group_id="O2">
            <title>No BFR</title>
            <description>This group of patients will undergo physical therapy exercises per the current standard of care after their ACL reconstruction without BFR&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
        </group_list>
        <measure>
          <title>Visual Analog Score</title>
          <description>The visual analog scale (VAS) is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between &quot;no pain&quot; and &quot;worst pain,&quot; with &quot;no pain&quot; corresponding to a VAS score of 0 and &quot;worst pain&quot; corresponding to a VAS score of 10.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Preoperative visit</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.36" spread="0.50"/>
                    <measurement group_id="O2" value="3.18" spread="1.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.72" spread="0.65"/>
                    <measurement group_id="O2" value="3.16" spread="0.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00" spread="0.26"/>
                    <measurement group_id="O2" value="1.51" spread="0.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.29" spread="0.30"/>
                    <measurement group_id="O2" value="1.16" spread="0.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis: there is no difference between groups in VAS score at 12 weeks post-op.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The a priori threshold for statistical significance was set at 0.05.</non_inferiority_desc>
            <p_value>0.008</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Quadriceps Tendon Strength</title>
        <description>We will measure quadriceps tendon strength (closed chain) strength using a hand-held dynamometer placed just distal to the knee joint on the posterior calf with the patient in the supine position. The outcome will be reported biweekly as a percentage of the strength of the contralateral side, and then finally reported as a change in strength from the first measurement to the final measurement. The results reported in this data table refer to the percent strength of the operated leg when compared to the contralateral side. The change in strength results can be found in the statistical analysis section.</description>
        <time_frame>Tracked from initiation of therapy 2 weeks post-op through 12 weeks post-op.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BFR Therapy</title>
            <description>This group will undergo physical therapy exercises per the standard of care, with the addition of Blood Flow Restriction (BFR) utilizing a wide pressure cuff. BFR exercises will be initiated two weeks post-op, and continued for 16 weeks.&#xD;
Blood Flow Restriction Therapy: A wide pressure cuff will be applied to the upper thigh prior to starting strengthening exercises. The cuff is inflated to 80% of resting systolic blood pressure. The cuff remains inflated for the entirety of the exercise (4 sets of a specific movement). Once the exercises are completed, it is deflated for a minimum of one minute before the next type of exercises are started.&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
          <group group_id="O2">
            <title>No BFR</title>
            <description>This group of patients will undergo physical therapy exercises per the current standard of care after their ACL reconstruction without BFR&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
        </group_list>
        <measure>
          <title>Quadriceps Tendon Strength</title>
          <description>We will measure quadriceps tendon strength (closed chain) strength using a hand-held dynamometer placed just distal to the knee joint on the posterior calf with the patient in the supine position. The outcome will be reported biweekly as a percentage of the strength of the contralateral side, and then finally reported as a change in strength from the first measurement to the final measurement. The results reported in this data table refer to the percent strength of the operated leg when compared to the contralateral side. The change in strength results can be found in the statistical analysis section.</description>
          <units>percent difference to contralateral side</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.88" spread="4.45"/>
                    <measurement group_id="O2" value="51.35" spread="5.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.68" spread="3.37"/>
                    <measurement group_id="O2" value="66.13" spread="3.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.73" spread="4.11"/>
                    <measurement group_id="O2" value="68.51" spread="3.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.39" spread="2.07"/>
                    <measurement group_id="O2" value="72.88" spread="3.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.22" spread="2.89"/>
                    <measurement group_id="O2" value="78.41" spread="5.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.47" spread="3.84"/>
                    <measurement group_id="O2" value="73.03" spread="5.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This analysis compares the change over time in quadriceps tendon strength between the BFR Therapy group and the No BFR Group. Underlying data was collected on a biweekly basis as the percent difference of the operated knee compared to the contralateral side. This statistical test utilized the null hypothesis that there would be no difference between groups in the change in quadriceps tendon strength over time.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The a priori threshold for statistical significance was set at 0.05.</non_inferiority_desc>
            <p_value>0.011</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Thigh Circumference</title>
        <description>A tape measure will be used to measure the thigh circumference 15 cm proximal to the superior pole of the patella. The outcome will be reported biweekly as a percentage of the contralateral side, and then finally reported as a change in circumference from the first measurement to the final measurement. The results reported in this data table refer to the percent circumference of the operated leg when compared to the contralateral side. The change in circumference results can be found in the statistical analysis section.</description>
        <time_frame>Tracked in the perioperative week and then from initiation of therapy 2 weeks post-op through 12 weeks post-op.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BFR Therapy</title>
            <description>This group will undergo physical therapy exercises per the standard of care, with the addition of Blood Flow Restriction (BFR) utilizing a wide pressure cuff. BFR exercises will be initiated two weeks post-op, and continued for 16 weeks.&#xD;
Blood Flow Restriction Therapy: A wide pressure cuff will be applied to the upper thigh prior to starting strengthening exercises. The cuff is inflated to 80% of resting systolic blood pressure. The cuff remains inflated for the entirety of the exercise (4 sets of a specific movement). Once the exercises are completed, it is deflated for a minimum of one minute before the next type of exercises are started.&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
          <group group_id="O2">
            <title>No BFR</title>
            <description>This group of patients will undergo physical therapy exercises per the current standard of care after their ACL reconstruction without BFR&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
        </group_list>
        <measure>
          <title>Thigh Circumference</title>
          <description>A tape measure will be used to measure the thigh circumference 15 cm proximal to the superior pole of the patella. The outcome will be reported biweekly as a percentage of the contralateral side, and then finally reported as a change in circumference from the first measurement to the final measurement. The results reported in this data table refer to the percent circumference of the operated leg when compared to the contralateral side. The change in circumference results can be found in the statistical analysis section.</description>
          <units>percent difference to contralateral side</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Perioperative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.23" spread="1.65"/>
                    <measurement group_id="O2" value="101.62" spread="2.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.02" spread="1.11"/>
                    <measurement group_id="O2" value="97.68" spread="1.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94.55" spread="0.82"/>
                    <measurement group_id="O2" value="97.11" spread="0.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.33" spread="1.05"/>
                    <measurement group_id="O2" value="95.55" spread="0.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.03" spread="0.71"/>
                    <measurement group_id="O2" value="95.76" spread="1.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>10 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.00" spread="0.71"/>
                    <measurement group_id="O2" value="96.46" spread="0.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.28" spread="0.61"/>
                    <measurement group_id="O2" value="98.27" spread="0.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This analysis compares the change over time in thigh circumference between the BFR Therapy group and the No BFR Group. Underlying data was collected on a biweekly basis as the percent difference of the operated knee compared to the contralateral side. This statistical test utilized the null hypothesis that there would be no difference between groups in the change in thigh circumference over time.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The a priori threshold for statistical significance was set at 0.05.</non_inferiority_desc>
            <p_value>0.223</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Degrees of Knee Flexion</title>
        <description>Degrees of knee flexion will be measured on the operative side by a licensed physical therapist. The outcome will be reported biweekly and then finally reported as a change in degrees from the first measurement to the final measurement. The results reported in this data table refer to the degrees of knee flexion at each reported time point. The change in knee flexion results can be found in the statistical analysis section.</description>
        <time_frame>Tracked in the perioperative week and then from initiation of therapy 2 weeks post-op through 12 weeks post-op.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BFR Therapy</title>
            <description>This group will undergo physical therapy exercises per the standard of care, with the addition of Blood Flow Restriction (BFR) utilizing a wide pressure cuff. BFR exercises will be initiated two weeks post-op, and continued for 16 weeks.&#xD;
Blood Flow Restriction Therapy: A wide pressure cuff will be applied to the upper thigh prior to starting strengthening exercises. The cuff is inflated to 80% of resting systolic blood pressure. The cuff remains inflated for the entirety of the exercise (4 sets of a specific movement). Once the exercises are completed, it is deflated for a minimum of one minute before the next type of exercises are started.&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
          <group group_id="O2">
            <title>No BFR</title>
            <description>This group of patients will undergo physical therapy exercises per the current standard of care after their ACL reconstruction without BFR&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
        </group_list>
        <measure>
          <title>Degrees of Knee Flexion</title>
          <description>Degrees of knee flexion will be measured on the operative side by a licensed physical therapist. The outcome will be reported biweekly and then finally reported as a change in degrees from the first measurement to the final measurement. The results reported in this data table refer to the degrees of knee flexion at each reported time point. The change in knee flexion results can be found in the statistical analysis section.</description>
          <units>degrees</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Perioperative Week</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.54" spread="4.43"/>
                    <measurement group_id="O2" value="41.9" spread="4.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.4" spread="3.53"/>
                    <measurement group_id="O2" value="70.00" spread="5.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="102.02" spread="3.07"/>
                    <measurement group_id="O2" value="91.75" spread="4.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="121.08" spread="2.73"/>
                    <measurement group_id="O2" value="112.74" spread="3.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="130.78" spread="2.74"/>
                    <measurement group_id="O2" value="126.22" spread="3.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>10 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="135.35" spread="2.19"/>
                    <measurement group_id="O2" value="130.12" spread="2.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="137.18" spread="2.20"/>
                    <measurement group_id="O2" value="130.50" spread="2.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This analysis compares the change over time in degrees of knee flexion between the BFR Therapy group and the No BFR Group from 2 weeks post-op to 12 weeks post-op. Underlying data was collected on a biweekly basis. This statistical test utilized the null hypothesis that there would be no difference between groups in the change in degrees of knee flexion over time.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The a priori threshold for statistical significance was set at 0.05.</non_inferiority_desc>
            <p_value>0.242</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Degrees of Knee Extension</title>
        <description>Degrees of knee extension will be measured on the operative side by a licensed physical therapist, with zero degrees indicating the knee completely at extension and negative degrees indicating degrees of hyperextension. The outcome will be reported biweekly and then finally reported as a change in degrees from the first measurement to the final measurement. The results reported in this data table refer to the degrees of knee extension at each reported time point. The change in knee extension results can be found in the statistical analysis section.</description>
        <time_frame>Tracked in the perioperative week and then from initiation of therapy 2 weeks post-op through 12 weeks post-op.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BFR Therapy</title>
            <description>This group will undergo physical therapy exercises per the standard of care, with the addition of Blood Flow Restriction (BFR) utilizing a wide pressure cuff. BFR exercises will be initiated two weeks post-op, and continued for 16 weeks.&#xD;
Blood Flow Restriction Therapy: A wide pressure cuff will be applied to the upper thigh prior to starting strengthening exercises. The cuff is inflated to 80% of resting systolic blood pressure. The cuff remains inflated for the entirety of the exercise (4 sets of a specific movement). Once the exercises are completed, it is deflated for a minimum of one minute before the next type of exercises are started.&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
          <group group_id="O2">
            <title>No BFR</title>
            <description>This group of patients will undergo physical therapy exercises per the current standard of care after their ACL reconstruction without BFR&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
        </group_list>
        <measure>
          <title>Degrees of Knee Extension</title>
          <description>Degrees of knee extension will be measured on the operative side by a licensed physical therapist, with zero degrees indicating the knee completely at extension and negative degrees indicating degrees of hyperextension. The outcome will be reported biweekly and then finally reported as a change in degrees from the first measurement to the final measurement. The results reported in this data table refer to the degrees of knee extension at each reported time point. The change in knee extension results can be found in the statistical analysis section.</description>
          <units>degrees</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Perioperative week</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.88" spread="1.40"/>
                    <measurement group_id="O2" value="-5.25" spread="1.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.60" spread="1.45"/>
                    <measurement group_id="O2" value="-3.20" spread="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.32" spread="0.73"/>
                    <measurement group_id="O2" value="-0.09" spread="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.68" spread="0.51"/>
                    <measurement group_id="O2" value="-0.15" spread="0.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.22" spread="0.64"/>
                    <measurement group_id="O2" value="0.63" spread="0.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>10 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.62" spread="0.68"/>
                    <measurement group_id="O2" value="0.33" spread="0.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 weeks post-op</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.59" spread="0.63"/>
                    <measurement group_id="O2" value="0.31" spread="0.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This analysis compares the change over time in degrees of knee extension between the BFR Therapy group and the No BFR Group from 2 weeks post-op to 12 weeks post-op. Underlying data was collected on a biweekly basis. This statistical test utilized the null hypothesis that there would be no difference between groups in the change in degrees of knee extension over time.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The a priori threshold for statistical significance was set at 0.05.</non_inferiority_desc>
            <p_value>0.049</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adverse Effects</title>
        <description>Observation of any adverse events associated with BFR therapy, such as numbness, cuff-site pain, and bruising.</description>
        <time_frame>Tracked from initiation of therapy 2 weeks post-op through 12 weeks post-op</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BFR Therapy</title>
            <description>This group will undergo physical therapy exercises per the standard of care, with the addition of Blood Flow Restriction (BFR) utilizing a wide pressure cuff. BFR exercises will be initiated two weeks post-op, and continued for 16 weeks.&#xD;
Blood Flow Restriction Therapy: A wide pressure cuff will be applied to the upper thigh prior to starting strengthening exercises. The cuff is inflated to 80% of resting systolic blood pressure. The cuff remains inflated for the entirety of the exercise (4 sets of a specific movement). Once the exercises are completed, it is deflated for a minimum of one minute before the next type of exercises are started.&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
          <group group_id="O2">
            <title>No BFR</title>
            <description>This group of patients will undergo physical therapy exercises per the current standard of care after their ACL reconstruction without BFR&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
          </group>
        </group_list>
        <measure>
          <title>Adverse Effects</title>
          <description>Observation of any adverse events associated with BFR therapy, such as numbness, cuff-site pain, and bruising.</description>
          <units>adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>BFR Therapy</title>
          <description>This group will undergo physical therapy exercises per the standard of care, with the addition of Blood Flow Restriction (BFR) utilizing a wide pressure cuff. BFR exercises will be initiated two weeks post-op, and continued for 16 weeks.&#xD;
Blood Flow Restriction Therapy: A wide pressure cuff will be applied to the upper thigh prior to starting strengthening exercises. The cuff is inflated to 80% of resting systolic blood pressure. The cuff remains inflated for the entirety of the exercise (4 sets of a specific movement). Once the exercises are completed, it is deflated for a minimum of one minute before the next type of exercises are started.&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
        </group>
        <group group_id="E2">
          <title>No BFR</title>
          <description>This group of patients will undergo physical therapy exercises per the current standard of care after their ACL reconstruction without BFR&#xD;
ACL Reconstruction rehabilitation: post-operative rehabilitation according to current standards of care</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Edward Chang</name_or_title>
      <organization>Inova Health System</organization>
      <phone>571-472-0464</phone>
      <email>edward.chang@inova.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03758755
org study id: 18-3150
nct id: NCT03758755
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
The main objective is to determine the impact of Blood Flow Restriction (BFR) therapy, in
      comparison to a standard rehabilitation protocol, on preventing atrophy, improving quadriceps
      strength and improving functional outcomes of patients recovering from ACL reconstruction.
      The investigators hypothesize that patients undergoing BFR therapy after ACL reconstruction
      surgery will have better functional outcomes than those undergoing normal rehabilitation
      without BFR therapy.
Recovery from anterior cruciate ligament (ACL) reconstruction involves early physical therapy
      to promote muscular development. Traditional training regimens are based on the concept that
      muscle growth is induced with high resistance exercises of at least 65-70% of 1-repetition
      maximum. Achieving a high resistance level can be challenging in the early post-surgical
      patient who may be limited by pain, muscle atrophy, diminished proprioception, and
      psychological factors. Increasing evidence has suggested that Blood Flow Restriction (BFR) in
      resistance training, while transmitting a decreased load (25-50% of 1-repetition maximum)
      across the surgical site, may provide an additional benefit of inducing muscular development
      similar to that of high intensity exercises .

      Augmenting exercises with BFR involves an external pressure cuff applied to the proximal
      portion of the extremity, which is inflated to a pressure that restricts venous outflow while
      allowing arterial inflow to continue. This creates a physiologic environment for the patient
      to gain the hypertrophic effect of high resistance training, though at a lower and safer
      intensity. Studies suggest that BFR stimulates muscular development through an increase in
      metabolic stress, muscle fiber recruitment, cell swelling, and protein synthesis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: International Knee Documentation Committee (IKDC) Questionnaire Score
time frame: Measured preoperatively and at 12 weeks post-op.
description: The International Knee Documentation Committee (IKDC Questionnaire) is a knee-specific patient-reported outcome measure. The IKDC Questionnaire is a subjective scale that provides patients with an overall function score. The questionnaire looks at 3 categories: symptoms, sports activity, and knee function. Scores are obtained by summing the individual items, then transforming the crude total to a scaled number that ranges from 0 to 100. This final number is interpreted as a measure of function with higher scores representing higher levels of function.
measure: Visual Analog Score
time frame: Measured preoperatively, at 2-weeks post-op, 6 weeks post-op, and 12 weeks post-op
description: The visual analog scale (VAS) is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" and "worst pain," with "no pain" corresponding to a VAS score of 0 and "worst pain" corresponding to a VAS score of 10.
measure: Quadriceps Tendon Strength
time frame: Tracked from initiation of therapy 2 weeks post-op through 12 weeks post-op.
description: We will measure quadriceps tendon strength (closed chain) strength using a hand-held dynamometer placed just distal to the knee joint on the posterior calf with the patient in the supine position. The outcome will be reported biweekly as a percentage of the strength of the contralateral side, and then finally reported as a change in strength from the first measurement to the final measurement. The results reported in this data table refer to the percent strength of the operated leg when compared to the contralateral side. The change in strength results can be found in the statistical analysis section.
measure: Thigh Circumference
time frame: Tracked in the perioperative week and then from initiation of therapy 2 weeks post-op through 12 weeks post-op.
description: A tape measure will be used to measure the thigh circumference 15 cm proximal to the superior pole of the patella. The outcome will be reported biweekly as a percentage of the contralateral side, and then finally reported as a change in circumference from the first measurement to the final measurement. The results reported in this data table refer to the percent circumference of the operated leg when compared to the contralateral side. The change in circumference results can be found in the statistical analysis section.
measure: Degrees of Knee Flexion
time frame: Tracked in the perioperative week and then from initiation of therapy 2 weeks post-op through 12 weeks post-op.
description: Degrees of knee flexion will be measured on the operative side by a licensed physical therapist. The outcome will be reported biweekly and then finally reported as a change in degrees from the first measurement to the final measurement. The results reported in this data table refer to the degrees of knee flexion at each reported time point. The change in knee flexion results can be found in the statistical analysis section.
measure: Degrees of Knee Extension
time frame: Tracked in the perioperative week and then from initiation of therapy 2 weeks post-op through 12 weeks post-op.
description: Degrees of knee extension will be measured on the operative side by a licensed physical therapist, with zero degrees indicating the knee completely at extension and negative degrees indicating degrees of hyperextension. The outcome will be reported biweekly and then finally reported as a change in degrees from the first measurement to the final measurement. The results reported in this data table refer to the degrees of knee extension at each reported time point. The change in knee extension results can be found in the statistical analysis section.
measure: Adverse Effects
time frame: Tracked from initiation of therapy 2 weeks post-op through 12 weeks post-op
description: Observation of any adverse events associated with BFR therapy, such as numbness, cuff-site pain, and bruising.
arm group label: BFR Therapy
arm group type: Experimental
description: This group will undergo physical therapy exercises per the standard of care, with the addition of Blood Flow Restriction (BFR) utilizing a wide pressure cuff. BFR exercises will be initiated two weeks post-op, and continued for 16 weeks.
arm group label: No BFR
arm group type: Active Comparator
description: This group of patients will undergo physical therapy exercises per the current standard of care after their ACL reconstruction without BFR
intervention type: Device
intervention name: Blood Flow Restriction Therapy
description: A wide pressure cuff will be applied to the upper thigh prior to starting strengthening exercises. The cuff is inflated to 80% of resting systolic blood pressure. The cuff remains inflated for the entirety of the exercise (4 sets of a specific movement). Once the exercises are completed, it is deflated for a minimum of one minute before the next type of exercises are started.
arm group label: BFR Therapy
intervention type: Other
intervention name: ACL Reconstruction rehabilitation
description: post-operative rehabilitation according to current standards of care
arm group label: BFR Therapy
arm group label: No BFR
criteria: 
gender: All
minimum age: 13 Years
maximum age: 50 Years
healthy volunteers: No
last name: Edward Chang, MD
role: Principal Investigator
affiliation: Orthopedic Surgeon
facility: 
country: United States
citation: Hughes L, Paton B, Rosenblatt B, Gissane C, Patterson SD. Blood flow restriction training in clinical musculoskeletal rehabilitation: a systematic review and meta-analysis. Br J Sports Med. 2017 Jul;51(13):1003-1011. doi: 10.1136/bjsports-2016-097071. Epub 2017 Mar 4.
PMID: 28259850
citation: Iversen E, Rostad V, Larmo A. Intermittent blood flow restriction does not reduce atrophy following anterior cruciate ligament reconstruction. J Sport Health Sci. 2016 Mar;5(1):115-118. doi: 10.1016/j.jshs.2014.12.005. Epub 2015 Apr 18.
PMID: 30356481
citation: Ohta H, Kurosawa H, Ikeda H, Iwase Y, Satou N, Nakamura S. Low-load resistance muscular training with moderate restriction of blood flow after anterior cruciate ligament reconstruction. Acta Orthop Scand. 2003 Feb;74(1):62-8. doi: 10.1080/00016470310013680.
PMID: 12635796
citation: Scott BR, Loenneke JP, Slattery KM, Dascombe BJ. Blood flow restricted exercise for athletes: A review of available evidence. J Sci Med Sport. 2016 May;19(5):360-7. doi: 10.1016/j.jsams.2015.04.014. Epub 2015 May 9.
PMID: 26118847
citation: Suga T, Okita K, Takada S, Omokawa M, Kadoguchi T, Yokota T, Hirabayashi K, Takahashi M, Morita N, Horiuchi M, Kinugawa S, Tsutsui H. Effect of multiple set on intramuscular metabolic stress during low-intensity resistance exercise with blood flow restriction. Eur J Appl Physiol. 2012 Nov;112(11):3915-20. doi: 10.1007/s00421-012-2377-x. Epub 2012 Mar 14.
PMID: 22415101
citation: Takada S, Okita K, Suga T, Omokawa M, Morita N, Horiuchi M, Kadoguchi T, Takahashi M, Hirabayashi K, Yokota T, Kinugawa S, Tsutsui H. Blood flow restriction exercise in sprinters and endurance runners. Med Sci Sports Exerc. 2012 Mar;44(3):413-9. doi: 10.1249/MSS.0b013e31822f39b3.
PMID: 21795999
citation: Takarada Y, Takazawa H, Sato Y, Takebayashi S, Tanaka Y, Ishii N. Effects of resistance exercise combined with moderate vascular occlusion on muscular function in humans. J Appl Physiol (1985). 2000 Jun;88(6):2097-106. doi: 10.1152/jappl.2000.88.6.2097.
PMID: 10846023
citation: Yasuda T, Brechue WF, Fujita T, Shirakawa J, Sato Y, Abe T. Muscle activation during low-intensity muscle contractions with restricted blood flow. J Sports Sci. 2009 Mar;27(5):479-89. doi: 10.1080/02640410802626567.
PMID: 19253083
responsible party type: Principal Investigator
investigator affiliation: Inova Health Care Services
investigator full name: Edward Chang, MD
investigator title: Orthopedic Surgeon
mesh term: Rupture
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 