<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/NCT03006562</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00123618</org_study_id>
    <nct_id>NCT03006562</nct_id>
  </id_info>
  <brief_title>PREvention of VENous ThromboEmbolism Following Radical Prostatectomy</brief_title>
  <acronym>PREVENTER</acronym>
  <official_title>A Randomized Controlled Trial for PREvention of VENous ThromboEmbolism Following Radical Prostatectomy (PREVENTER Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</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>
      The PREVENTER Trial aims to compare the use of perioperative pharmacologic prophylaxis&#xD;
      (subcutaneous heparin) with intermittent pneumatic compression devices (IPCs) to the use of&#xD;
      IPCs alone for the prevention of venous thromboembolism (VTE) after radical prostatectomy&#xD;
      (RP).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The PREVENTER Trial aims to compare the use of perioperative pharmacologic prophylaxis&#xD;
      (subcutaneous heparin) with intermittent pneumatic compression devices (IPCs) to the use of&#xD;
      IPCs alone for the prevention of venous thromboembolism (VTE) after radical prostatectomy&#xD;
      (RP). Currently, there is no standard practice for VTE prophylaxis after RP with the American&#xD;
      Urological Association recommending &quot;pharmacological or pneumatic mechanical prophylaxis&quot; for&#xD;
      high risk patients. Prior studies showed 30% of patients in the United States received no&#xD;
      perioperative prophylaxis and less than 20% received pharmacologic agents, compared to 98% of&#xD;
      patients receiving pharmacologic prophylaxis in the United Kingdom. Some urologists prescribe&#xD;
      patients low molecular weight heparin (LMWH) after discharge for up to 30 days after surgery.&#xD;
      Additionally, there are no established risks of pharmacologic prophylaxis for RP patients,&#xD;
      but some urologists express concern about the potential impact of prophylaxis on the rate of&#xD;
      postoperative lymphoceles or hematomas. At Johns Hopkins, patients do not routinely receive&#xD;
      pharmacologic VTE prophylaxis in the perioperative setting for RP. Given the lack of standard&#xD;
      practice and implications for patient safety, the investigators propose a prospective,&#xD;
      stratified randomized controlled trial to evaluate the impact of perioperative pharmacologic&#xD;
      prophylaxis on VTE following RP hypothesizing that it will prevent VTE events without&#xD;
      significantly impacting the rate of postoperative bleeding or lymphoceles. The potential&#xD;
      impact of surveillance bias with differential imaging between arms, effect of lymphadenectomy&#xD;
      (yes/no and number of noted removed) or surgical approach (robotic and open), and differences&#xD;
      by patients risk (comorbidity and VTE risk based on components of the Caprini score) or&#xD;
      demographics will be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Early stopping point based on 2nd interim analysis (planned per protocol)&#xD;
  </why_stopped>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Actual">November 1, 2019</completion_date>
  <primary_completion_date type="Actual">November 1, 2019</primary_completion_date>
  <phase>Phase 4</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>Prospective, single-institution, multi-surgeon, stratified randomized controlled trial. Randomization will be stratified into four groups by procedure approach (open or robotic) and whether patients elect to undergo a screening 30-day lower extremity Duplex (ultrasound or no ultrasound). Patients will then be randomized, within each of the strata, to the two arms (subcutaneous heparin versus no subcutaneous heparin).</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Symptomatic Venous Thromboembolism</measure>
    <time_frame>30 days</time_frame>
    <description>Venous thromboembolism (VTE) is a disease that includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). The primary outcome is diagnosis of DVT or PE within 30 days after surgery due to imaging (any method, most commonly lower extremity ultrasound or computed tomography scan with pulmonary embolus protocol) prompted by symptoms of a DVT (lower extremity swelling, pain, fever of unknown origin) or PE (chest pain, shortness of breath, hypoxemia, tachycardia or fever of unknown origin, productive cough with bloody sputum).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Symptomatic Postoperative Fluid Collection</measure>
    <time_frame>30 days</time_frame>
    <description>This outcome is defined as a surgical or pelvic fluid collection diagnosed as a hematoma (blood collection, with or without infection) or lymphocele (collection of lymph fluid in the pelvis) due to symptoms (fever, abdominal pain, nausea or vomiting, anemia, high surgical drain output) within 30 days after surgery.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Major Postoperative Bleeding</measure>
    <time_frame>30 days</time_frame>
    <description>This additional primary outcome includes the development and diagnosis of any major clinically recognized bleeding event within 30 days after surgery requiring &gt;1 unit of packed red blood cell transfusion, intervention to stop bleeding, or return to the operating room.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Occurrence of Any Venous Thromboembolism</measure>
    <time_frame>30 days</time_frame>
    <description>DVT or PE diagnosed for any reason within 30 days after surgery. This includes any diagnosed DVT or PE as described in the primary outcome plus any additional DVTs or PEs diagnosed at 30 day screening lower extremity ultrasound for patients opting to undergo screening bilateral lower extremity Duplex ultrasound at 30 days who do not have symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estimated Blood Loss During Surgery</measure>
    <time_frame>During surgery (usually between 2-3 hours of operative time)</time_frame>
    <description>The total recorded intraoperative estimated blood loss in milliliters reported at the end of the surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical Drain Output After Surgery</measure>
    <time_frame>Over length of stay in hospital (usually 1 to 2 days)</time_frame>
    <description>The total output in milliliters from any surgical drain left in place (not all patients will necessarily have a surgical drain) after surgery and until discharge from the hospital (usually 1 to 2 days). Drain output, if one is left in place after discharge, will not count toward this secondary outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surveillance Bias by Differential Use of Imaging as Assessed by Number of Participants Receiving Postoperative Diagnostic Imaging for Venous Thromboembolism Relative to Symptoms</measure>
    <time_frame>30 days</time_frame>
    <description>Patients in each arm receiving postoperative diagnostic imaging for venous thromboembolism relative to symptoms (e.g. lower extremity Duplex ultrasound, spiral CT angiography, V/Q scan).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">501</enrollment>
  <condition>Prostate Cancer</condition>
  <condition>Venous Thromboembolism</condition>
  <condition>Lymphocele After Surgical Procedure</condition>
  <condition>Deep Venous Thrombosis</condition>
  <condition>Pulmonary Embolism</condition>
  <arm_group>
    <arm_group_label>Subcutaneous Heparin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to the pharmacologic VTE prophylaxis arm will receive a dose of subcutaneous heparin 5,000 units prior to incision, and subcutaneous heparin 5,000 units every 8 hours after surgery until discharge.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Subcutaneous Heparin</intervention_name>
    <description>5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.</description>
    <arm_group_label>Subcutaneous Heparin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men 18-100 years of age with histologically confirmed prostate cancer of any stage&#xD;
             undergoing RP&#xD;
&#xD;
          -  Patients who would have otherwise been eligible to receive routine post-RP care&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active treatment for VTE&#xD;
&#xD;
          -  Patients judged by patients' urologist, primary care doctor, or in the preoperative&#xD;
             evaluation center (PEC) to be unsafe to forgo pharmacologic prophylaxis or systemic&#xD;
             anticoagulation postoperatively (whether or not patients are on systematic&#xD;
             anticoagulation for indications other than VTE)&#xD;
&#xD;
          -  Known adverse reactions to heparin (heparin-induced thrombocytopenia or any allergy)&#xD;
&#xD;
          -  Epidural analgesia&#xD;
&#xD;
          -  Spinal anesthesia&#xD;
&#xD;
          -  Participation in a different trial that increases a patient's risk of VTE&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mohamad E Allaf, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Huang MM, Su ZT, Becker REN, Pavlovich CP, Partin AW, Allaf ME, Patel HD. Complications after open and robot-assisted radical prostatectomy and association with postoperative opioid use: an analysis of data from the PREVENTER trial. BJU Int. 2021 Feb;127(2):190-197. doi: 10.1111/bju.15172. Epub 2020 Aug 17.</citation>
    <PMID>32654363</PMID>
  </reference>
  <results_reference>
    <citation>Patel HD, Faisal FA, Trock BJ, Joice GA, Schwen ZR, Pierorazio PM, Johnson MH, Bivalacqua TJ, Han M, Gorin MA, Carter HB, Partin AW, Pavlovich CP, Allaf ME. Effect of Pharmacologic Prophylaxis on Venous Thromboembolism After Radical Prostatectomy: The PREVENTER Randomized Clinical Trial. Eur Urol. 2020 Sep;78(3):360-368. doi: 10.1016/j.eururo.2020.05.001. Epub 2020 May 19.</citation>
    <PMID>32444264</PMID>
  </results_reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>December 27, 2016</study_first_submitted>
  <study_first_submitted_qc>December 27, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 30, 2016</study_first_posted>
  <results_first_submitted>February 7, 2020</results_first_submitted>
  <results_first_submitted_qc>February 26, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">February 28, 2020</results_first_posted>
  <last_update_submitted>July 27, 2020</last_update_submitted>
  <last_update_submitted_qc>July 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphocele</mesh_term>
    <mesh_term>Pulmonary Embolism</mesh_term>
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Embolism</mesh_term>
    <mesh_term>Thromboembolism</mesh_term>
    <mesh_term>Venous Thromboembolism</mesh_term>
    <mesh_term>Venous Thrombosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heparin</mesh_term>
  </intervention_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>April 4, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/62/NCT03006562/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Subcutaneous Heparin</title>
          <description>Patients randomized to the pharmacologic VTE prophylaxis arm will receive a dose of subcutaneous heparin 5,000 units prior to incision, and subcutaneous heparin 5,000 units every 8 hours after surgery until discharge.&#xD;
Subcutaneous Heparin: 5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.</description>
        </group>
        <group group_id="P2">
          <title>Control</title>
          <description>Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="251"/>
                <participants group_id="P2" count="250"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Voluntary Ultrasound at 30 Days</title>
              <participants_list>
                <participants group_id="P1" count="141"/>
                <participants group_id="P2" count="137"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="251"/>
                <participants group_id="P2" count="249"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Subcutaneous Heparin</title>
          <description>Patients randomized to the pharmacologic VTE prophylaxis arm will receive a dose of subcutaneous heparin 5,000 units prior to incision, and subcutaneous heparin 5,000 units every 8 hours after surgery until discharge.&#xD;
Subcutaneous Heparin: 5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.</description>
        </group>
        <group group_id="B2">
          <title>Control</title>
          <description>Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices.</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="251"/>
            <count group_id="B2" value="250"/>
            <count group_id="B3" value="501"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63" lower_limit="57" upper_limit="67"/>
                    <measurement group_id="B2" value="61" lower_limit="56" upper_limit="67"/>
                    <measurement group_id="B3" value="62" lower_limit="57" upper_limit="67"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="251"/>
                    <measurement group_id="B2" value="250"/>
                    <measurement group_id="B3" value="501"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="200"/>
                    <measurement group_id="B2" value="204"/>
                    <measurement group_id="B3" value="404"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Symptomatic Venous Thromboembolism</title>
        <description>Venous thromboembolism (VTE) is a disease that includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). The primary outcome is diagnosis of DVT or PE within 30 days after surgery due to imaging (any method, most commonly lower extremity ultrasound or computed tomography scan with pulmonary embolus protocol) prompted by symptoms of a DVT (lower extremity swelling, pain, fever of unknown origin) or PE (chest pain, shortness of breath, hypoxemia, tachycardia or fever of unknown origin, productive cough with bloody sputum).</description>
        <time_frame>30 days</time_frame>
        <population>One participant in the control arm was lost to follow-up precluding outcome assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Subcutaneous Heparin</title>
            <description>Patients randomized to the pharmacologic VTE prophylaxis arm will receive a dose of subcutaneous heparin 5,000 units prior to incision, and subcutaneous heparin 5,000 units every 8 hours after surgery until discharge.&#xD;
Subcutaneous Heparin: 5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Symptomatic Venous Thromboembolism</title>
          <description>Venous thromboembolism (VTE) is a disease that includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). The primary outcome is diagnosis of DVT or PE within 30 days after surgery due to imaging (any method, most commonly lower extremity ultrasound or computed tomography scan with pulmonary embolus protocol) prompted by symptoms of a DVT (lower extremity swelling, pain, fever of unknown origin) or PE (chest pain, shortness of breath, hypoxemia, tachycardia or fever of unknown origin, productive cough with bloody sputum).</description>
          <population>One participant in the control arm was lost to follow-up precluding outcome assessment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="251"/>
                <count group_id="O2" value="249"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Symptomatic Postoperative Fluid Collection</title>
        <description>This outcome is defined as a surgical or pelvic fluid collection diagnosed as a hematoma (blood collection, with or without infection) or lymphocele (collection of lymph fluid in the pelvis) due to symptoms (fever, abdominal pain, nausea or vomiting, anemia, high surgical drain output) within 30 days after surgery.</description>
        <time_frame>30 days</time_frame>
        <population>One participant in the control arm was lost to follow-up precluding outcome assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Subcutaneous Heparin</title>
            <description>Patients randomized to the pharmacologic VTE prophylaxis arm will receive a dose of subcutaneous heparin 5,000 units prior to incision, and subcutaneous heparin 5,000 units every 8 hours after surgery until discharge.&#xD;
Subcutaneous Heparin: 5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Symptomatic Postoperative Fluid Collection</title>
          <description>This outcome is defined as a surgical or pelvic fluid collection diagnosed as a hematoma (blood collection, with or without infection) or lymphocele (collection of lymph fluid in the pelvis) due to symptoms (fever, abdominal pain, nausea or vomiting, anemia, high surgical drain output) within 30 days after surgery.</description>
          <population>One participant in the control arm was lost to follow-up precluding outcome assessment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="251"/>
                <count group_id="O2" value="249"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Major Postoperative Bleeding</title>
        <description>This additional primary outcome includes the development and diagnosis of any major clinically recognized bleeding event within 30 days after surgery requiring &gt;1 unit of packed red blood cell transfusion, intervention to stop bleeding, or return to the operating room.</description>
        <time_frame>30 days</time_frame>
        <population>One participant in the control arm was lost to follow-up precluding outcome assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Subcutaneous Heparin</title>
            <description>Patients randomized to the pharmacologic VTE prophylaxis arm will receive a dose of subcutaneous heparin 5,000 units prior to incision, and subcutaneous heparin 5,000 units every 8 hours after surgery until discharge.&#xD;
Subcutaneous Heparin: 5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Major Postoperative Bleeding</title>
          <description>This additional primary outcome includes the development and diagnosis of any major clinically recognized bleeding event within 30 days after surgery requiring &gt;1 unit of packed red blood cell transfusion, intervention to stop bleeding, or return to the operating room.</description>
          <population>One participant in the control arm was lost to follow-up precluding outcome assessment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="251"/>
                <count group_id="O2" value="249"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Occurrence of Any Venous Thromboembolism</title>
        <description>DVT or PE diagnosed for any reason within 30 days after surgery. This includes any diagnosed DVT or PE as described in the primary outcome plus any additional DVTs or PEs diagnosed at 30 day screening lower extremity ultrasound for patients opting to undergo screening bilateral lower extremity Duplex ultrasound at 30 days who do not have symptoms.</description>
        <time_frame>30 days</time_frame>
        <population>Only the subset receiving ultrasound are analyzed for this outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>Subcutaneous Heparin</title>
            <description>Patients randomized to the pharmacologic VTE prophylaxis arm will receive a dose of subcutaneous heparin 5,000 units prior to incision, and subcutaneous heparin 5,000 units every 8 hours after surgery until discharge.&#xD;
Subcutaneous Heparin: 5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Occurrence of Any Venous Thromboembolism</title>
          <description>DVT or PE diagnosed for any reason within 30 days after surgery. This includes any diagnosed DVT or PE as described in the primary outcome plus any additional DVTs or PEs diagnosed at 30 day screening lower extremity ultrasound for patients opting to undergo screening bilateral lower extremity Duplex ultrasound at 30 days who do not have symptoms.</description>
          <population>Only the subset receiving ultrasound are analyzed for this outcome.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="141"/>
                <count group_id="O2" value="137"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Estimated Blood Loss During Surgery</title>
        <description>The total recorded intraoperative estimated blood loss in milliliters reported at the end of the surgery.</description>
        <time_frame>During surgery (usually between 2-3 hours of operative time)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Subcutaneous Heparin</title>
            <description>Patients randomized to the pharmacologic VTE prophylaxis arm will receive a dose of subcutaneous heparin 5,000 units prior to incision, and subcutaneous heparin 5,000 units every 8 hours after surgery until discharge.&#xD;
Subcutaneous Heparin: 5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices.</description>
          </group>
        </group_list>
        <measure>
          <title>Estimated Blood Loss During Surgery</title>
          <description>The total recorded intraoperative estimated blood loss in milliliters reported at the end of the surgery.</description>
          <units>milliliters</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="251"/>
                <count group_id="O2" value="250"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="150" lower_limit="100" upper_limit="300"/>
                    <measurement group_id="O2" value="200" lower_limit="100" upper_limit="300"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Surgical Drain Output After Surgery</title>
        <description>The total output in milliliters from any surgical drain left in place (not all patients will necessarily have a surgical drain) after surgery and until discharge from the hospital (usually 1 to 2 days). Drain output, if one is left in place after discharge, will not count toward this secondary outcome.</description>
        <time_frame>Over length of stay in hospital (usually 1 to 2 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Subcutaneous Heparin</title>
            <description>Patients randomized to the pharmacologic VTE prophylaxis arm will receive a dose of subcutaneous heparin 5,000 units prior to incision, and subcutaneous heparin 5,000 units every 8 hours after surgery until discharge.&#xD;
Subcutaneous Heparin: 5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices.</description>
          </group>
        </group_list>
        <measure>
          <title>Surgical Drain Output After Surgery</title>
          <description>The total output in milliliters from any surgical drain left in place (not all patients will necessarily have a surgical drain) after surgery and until discharge from the hospital (usually 1 to 2 days). Drain output, if one is left in place after discharge, will not count toward this secondary outcome.</description>
          <units>milliliters</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="251"/>
                <count group_id="O2" value="250"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95" lower_limit="60" upper_limit="180"/>
                    <measurement group_id="O2" value="100" lower_limit="54" upper_limit="150"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Surveillance Bias by Differential Use of Imaging as Assessed by Number of Participants Receiving Postoperative Diagnostic Imaging for Venous Thromboembolism Relative to Symptoms</title>
        <description>Patients in each arm receiving postoperative diagnostic imaging for venous thromboembolism relative to symptoms (e.g. lower extremity Duplex ultrasound, spiral CT angiography, V/Q scan).</description>
        <time_frame>30 days</time_frame>
        <population>One participant in the control arm was lost to follow-up precluding outcome assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Subcutaneous Heparin</title>
            <description>Patients randomized to the pharmacologic VTE prophylaxis arm will receive a dose of subcutaneous heparin 5,000 units prior to incision, and subcutaneous heparin 5,000 units every 8 hours after surgery until discharge.&#xD;
Subcutaneous Heparin: 5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices.</description>
          </group>
        </group_list>
        <measure>
          <title>Surveillance Bias by Differential Use of Imaging as Assessed by Number of Participants Receiving Postoperative Diagnostic Imaging for Venous Thromboembolism Relative to Symptoms</title>
          <description>Patients in each arm receiving postoperative diagnostic imaging for venous thromboembolism relative to symptoms (e.g. lower extremity Duplex ultrasound, spiral CT angiography, V/Q scan).</description>
          <population>One participant in the control arm was lost to follow-up precluding outcome assessment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="251"/>
                <count group_id="O2" value="249"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>30 days</time_frame>
      <desc>Clavien-Dindo Complications</desc>
      <group_list>
        <group group_id="E1">
          <title>Subcutaneous Heparin</title>
          <description>Patients randomized to the pharmacologic VTE prophylaxis arm will receive a dose of subcutaneous heparin 5,000 units prior to incision, and subcutaneous heparin 5,000 units every 8 hours after surgery until discharge.&#xD;
Subcutaneous Heparin: 5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.</description>
        </group>
        <group group_id="E2">
          <title>Control</title>
          <description>Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="250"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="250"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Clavien III or Greater Complication</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="251"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="250"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="250"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Clavien I or II Complication</sub_title>
                <counts group_id="E1" events="34" subjects_affected="34" subjects_at_risk="251"/>
                <counts group_id="E2" events="30" subjects_affected="30" subjects_at_risk="250"/>
              </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>
    <limitations_and_caveats>The study met a futility end point at the 2nd interim analysis (pre-planned in the study protocol) leading to an appropriate decision for early closure and termination rather than continuing to planned enrollment of N=666.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Mohamad Allaf</name_or_title>
      <organization>Johns Hopkins Brady Urological Institute</organization>
      <phone>410-955-6100</phone>
      <email>mallaf@jhmi.edu</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/NCT03006562
org study id: IRB00123618
nct id: NCT03006562
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The PREVENTER Trial aims to compare the use of perioperative pharmacologic prophylaxis
      (subcutaneous heparin) with intermittent pneumatic compression devices (IPCs) to the use of
      IPCs alone for the prevention of venous thromboembolism (VTE) after radical prostatectomy
      (RP).
The PREVENTER Trial aims to compare the use of perioperative pharmacologic prophylaxis
      (subcutaneous heparin) with intermittent pneumatic compression devices (IPCs) to the use of
      IPCs alone for the prevention of venous thromboembolism (VTE) after radical prostatectomy
      (RP). Currently, there is no standard practice for VTE prophylaxis after RP with the American
      Urological Association recommending "pharmacological or pneumatic mechanical prophylaxis" for
      high risk patients. Prior studies showed 30% of patients in the United States received no
      perioperative prophylaxis and less than 20% received pharmacologic agents, compared to 98% of
      patients receiving pharmacologic prophylaxis in the United Kingdom. Some urologists prescribe
      patients low molecular weight heparin (LMWH) after discharge for up to 30 days after surgery.
      Additionally, there are no established risks of pharmacologic prophylaxis for RP patients,
      but some urologists express concern about the potential impact of prophylaxis on the rate of
      postoperative lymphoceles or hematomas. At Johns Hopkins, patients do not routinely receive
      pharmacologic VTE prophylaxis in the perioperative setting for RP. Given the lack of standard
      practice and implications for patient safety, the investigators propose a prospective,
      stratified randomized controlled trial to evaluate the impact of perioperative pharmacologic
      prophylaxis on VTE following RP hypothesizing that it will prevent VTE events without
      significantly impacting the rate of postoperative bleeding or lymphoceles. The potential
      impact of surveillance bias with differential imaging between arms, effect of lymphadenectomy
      (yes/no and number of noted removed) or surgical approach (robotic and open), and differences
      by patients risk (comorbidity and VTE risk based on components of the Caprini score) or
      demographics will be assessed.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective, single-institution, multi-surgeon, stratified randomized controlled trial. Randomization will be stratified into four groups by procedure approach (open or robotic) and whether patients elect to undergo a screening 30-day lower extremity Duplex (ultrasound or no ultrasound). Patients will then be randomized, within each of the strata, to the two arms (subcutaneous heparin versus no subcutaneous heparin).
primary purpose: Prevention
masking: Single (Outcomes Assessor)
measure: Number of Participants With Symptomatic Venous Thromboembolism
time frame: 30 days
description: Venous thromboembolism (VTE) is a disease that includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). The primary outcome is diagnosis of DVT or PE within 30 days after surgery due to imaging (any method, most commonly lower extremity ultrasound or computed tomography scan with pulmonary embolus protocol) prompted by symptoms of a DVT (lower extremity swelling, pain, fever of unknown origin) or PE (chest pain, shortness of breath, hypoxemia, tachycardia or fever of unknown origin, productive cough with bloody sputum).
measure: Number of Participants With Symptomatic Postoperative Fluid Collection
time frame: 30 days
description: This outcome is defined as a surgical or pelvic fluid collection diagnosed as a hematoma (blood collection, with or without infection) or lymphocele (collection of lymph fluid in the pelvis) due to symptoms (fever, abdominal pain, nausea or vomiting, anemia, high surgical drain output) within 30 days after surgery.
measure: Number of Participants With Major Postoperative Bleeding
time frame: 30 days
description: This additional primary outcome includes the development and diagnosis of any major clinically recognized bleeding event within 30 days after surgery requiring >1 unit of packed red blood cell transfusion, intervention to stop bleeding, or return to the operating room.
measure: Number of Participants With Occurrence of Any Venous Thromboembolism
time frame: 30 days
description: DVT or PE diagnosed for any reason within 30 days after surgery. This includes any diagnosed DVT or PE as described in the primary outcome plus any additional DVTs or PEs diagnosed at 30 day screening lower extremity ultrasound for patients opting to undergo screening bilateral lower extremity Duplex ultrasound at 30 days who do not have symptoms.
measure: Estimated Blood Loss During Surgery
time frame: During surgery (usually between 2-3 hours of operative time)
description: The total recorded intraoperative estimated blood loss in milliliters reported at the end of the surgery.
measure: Surgical Drain Output After Surgery
time frame: Over length of stay in hospital (usually 1 to 2 days)
description: The total output in milliliters from any surgical drain left in place (not all patients will necessarily have a surgical drain) after surgery and until discharge from the hospital (usually 1 to 2 days). Drain output, if one is left in place after discharge, will not count toward this secondary outcome.
measure: Surveillance Bias by Differential Use of Imaging as Assessed by Number of Participants Receiving Postoperative Diagnostic Imaging for Venous Thromboembolism Relative to Symptoms
time frame: 30 days
description: Patients in each arm receiving postoperative diagnostic imaging for venous thromboembolism relative to symptoms (e.g. lower extremity Duplex ultrasound, spiral CT angiography, V/Q scan).
arm group label: Subcutaneous Heparin
arm group type: Experimental
description: Patients randomized to the pharmacologic VTE prophylaxis arm will receive a dose of subcutaneous heparin 5,000 units prior to incision, and subcutaneous heparin 5,000 units every 8 hours after surgery until discharge.
arm group label: Control
arm group type: No Intervention
description: Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices.
intervention type: Drug
intervention name: Subcutaneous Heparin
description: 5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.
arm group label: Subcutaneous Heparin
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Mohamad E Allaf, MD
role: Principal Investigator
affiliation: Johns Hopkins University
facility: 
country: United States
citation: Huang MM, Su ZT, Becker REN, Pavlovich CP, Partin AW, Allaf ME, Patel HD. Complications after open and robot-assisted radical prostatectomy and association with postoperative opioid use: an analysis of data from the PREVENTER trial. BJU Int. 2021 Feb;127(2):190-197. doi: 10.1111/bju.15172. Epub 2020 Aug 17.
PMID: 32654363
citation: Patel HD, Faisal FA, Trock BJ, Joice GA, Schwen ZR, Pierorazio PM, Johnson MH, Bivalacqua TJ, Han M, Gorin MA, Carter HB, Partin AW, Pavlovich CP, Allaf ME. Effect of Pharmacologic Prophylaxis on Venous Thromboembolism After Radical Prostatectomy: The PREVENTER Randomized Clinical Trial. Eur Urol. 2020 Sep;78(3):360-368. doi: 10.1016/j.eururo.2020.05.001. Epub 2020 May 19.
PMID: 32444264
responsible party type: Sponsor
mesh term: Lymphocele
mesh term: Pulmonary Embolism
mesh term: Thrombosis
mesh term: Embolism
mesh term: Thromboembolism
mesh term: Venous Thromboembolism
mesh term: Venous Thrombosis
mesh term: Heparin
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study met a futility end point at the 2nd interim analysis (pre-planned in the study protocol) leading to an appropriate decision for early closure and termination rather than continuing to planned enrollment of N=666.
point of contact: 