<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/NCT03831386</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00158671</org_study_id>
    <nct_id>NCT03831386</nct_id>
  </id_info>
  <brief_title>Gravity Versus Vacuum Based Indwelling Tunneled Pleural Drainage System</brief_title>
  <acronym>NEWTON</acronym>
  <official_title>The Impact of a Gravity Versus Vacuum Based Indwelling Tunneled Pleural Drainage System on Pain: A Multicenter, Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rocket Medical plc</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Swedish Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical University of South Carolina</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Northwest Community Healthcare</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Malignant pleural effusion remains a debilitating complication of end stage cancer, which can&#xD;
      be greatly improved by the introduction of the indwelling tunneled pleural catheter (IPC).&#xD;
      However, there is no standard of care regarding drainage and limited data on the utility of&#xD;
      different drainage techniques. In addition, many patients develop discomfort and chest pain&#xD;
      during drainage. The investigators propose to evaluate gravity drainage and suction drainage&#xD;
      on quality of life measures and outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Indwelling tunneled pleural catheters (IPCs) are used to alleviate pleural effusion as a&#xD;
      first-line therapeutic (albeit palliative) intervention. Limited data currently exists on&#xD;
      drainage techniques and the impact the techniques may have on quality of life. Current&#xD;
      recommendations for IPC drainage range from daily drainage to once a week drainage, as well&#xD;
      as only when needed for dyspnea. It has been theorized that active drainage of effusions may&#xD;
      have an impact on the development of chest discomfort/pain, whereas passive regimens may&#xD;
      allow for more gradual intrathoracic pleural changes and potentially offer a difference in&#xD;
      drainage discomfort.&#xD;
&#xD;
      The objective of this investigation is to compare different drainage strategies of indwelling&#xD;
      pleural catheters (IPCs) regarding patient quality of life and outcomes. Patients will&#xD;
      undergo placement of a pleural catheter as per standard institutional protocol. Patients will&#xD;
      be randomized on a 1:1 basis into the suction drainage (active) arm or the gravity drainage&#xD;
      (passive) arm. Patients will receive follow-up at two weeks, four weeks, twelve weeks and&#xD;
      then as needed post IPC placement per standard clinical protocol. All patients will be asked&#xD;
      to fill out quality of life questionnaires and update drainage diary information with&#xD;
      patient's providers.&#xD;
&#xD;
      Patients will undergo standard care treatment throughout the disease course and no different&#xD;
      interventions regarding the pleural disease will be performed as a result of enrollment&#xD;
      within this study. Study interventions/procedures will consist of questionnaires and patient&#xD;
      self-reported documentation regarding patient's care and outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 31, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</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>Change in chest pain as assessed by Visual Analog Scale (VAS)</measure>
    <time_frame>Daily, up to 2 weeks</time_frame>
    <description>The primary endpoint is the difference between the mean daily change in pain score during IPC drainage via the vacuum bottle technique and IPC drainage via the gravity bag technique over two weeks after IPC placement. Pre-drainage and post-drainage pain scores will be recorded each day of IPC placement. Measurements are in millimeters along a 10 cm VAS. VAS score is a range of 0 to 100. Lower limit is 0, meaning no pain; upper limit is 100, meaning extreme pain.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in mean difference in chest pain as assessed by VAS</measure>
    <time_frame>pre-IPC placement, 12 weeks post IPC placement or time of pleurodesis</time_frame>
    <description>This secondary endpoint is the difference between the change in pain scores via vacuum bottle vs. gravity bag pre-IPC placement to the last available score after IPC placement. This last available score would be at 12 weeks or time of pleurodesis. Measurements are in millimeters along a 10 cm Visual Analog Scale (VAS). VAS score is a range of 0 to 100. Lower limit is 0, meaning no pain; upper limit is 100, meaning extreme pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SF 36-Item Health Survey score</measure>
    <time_frame>pre-IPC placement, 12 weeks post IPC placement or time of pleurodesis</time_frame>
    <description>This secondary endpoint is the difference between SF 36-Item Health Survey 1.0 scores via vacuum bottle vs. gravity bag from pre-IPC drainage to last available score after IPC placement (at 12 weeks or time of pleurodesis). Scoring is a 2-step process in which the numerical response from the Survey is first converted into a 0-100 scale (0 as lowest and 100 as highest possible score) using a conversion table by SF developers. These new values would be averaged according to their group identified in a second conversion table.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Functional Assessment of Chronic Illness Therapy (FACIT)-Dyspnea survey score</measure>
    <time_frame>pre-IPC placement, 12 weeks post IPC placement or time of pleurodesis</time_frame>
    <description>This secondary endpoint is the difference between FACIT-Dyspnea scores via vacuum bottle vs. gravity bag from pre-IPC drainage to the last available score after IPC placement (at 12 weeks or time of pleurodesis). Individual responses are converted into scores, then summed for an overall score. Scores range from 0 (lower limit) to 30 (high limit); the higher the score, the worse the dyspnea.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Pleural Effusion</condition>
  <arm_group>
    <arm_group_label>Vacuum</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The pleural fluid will be drained by the syringe system with a one-way valve tubing system provided in the kit. Selection of the vacuum pressure will be at the discretion of the proceduralist, as per standard of care. Participants in this arm will undergo Vacuum-Based IPC.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gravity</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The pleural fluid will be drained using gravity drainage to a bag positioned at bedside. Participants in this arm will undergo Gravity-Based IPC.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Vacuum-Based IPC</intervention_name>
    <description>An indwelling pleural catheter is placed inside the chest cavity to drain fluid from around the lungs. One end remains inside the body while the other drains via suction.</description>
    <arm_group_label>Vacuum</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Gravity-Based IPC</intervention_name>
    <description>An indwelling pleural catheter is placed inside the chest cavity to drain fluid from around the lungs. One end remains inside the body while the other drains via gravity.</description>
    <arm_group_label>Gravity</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical indications for placement of IPC for malignant pleural effusion&#xD;
&#xD;
             a. Pleural effusion with symptomatic improvement in dyspnea after drainage of&#xD;
             ipsilateral effusion&#xD;
&#xD;
          -  Clinically confident symptomatic malignant pleural effusion&#xD;
&#xD;
               1. Histocytological proof of pleural malignancy&#xD;
&#xD;
               2. Recurrent large pleural effusion in context of histologically proven cancer&#xD;
                  outside the pleural space&#xD;
&#xD;
          -  Plans for placement of IPC within ten days of enrollment&#xD;
&#xD;
          -  Age &gt; 17 years&#xD;
&#xD;
          -  Sufficient fluid on ultrasound to allow for safe insertion of IPC&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Recent (less than 60 days) thoracic surgery or chest trauma causing chronic pain&#xD;
&#xD;
          -  Pregnant or lactating mothers&#xD;
&#xD;
          -  Previous ipsilateral chemical pleurodesis&#xD;
&#xD;
          -  Current contralateral indwelling pleural catheter&#xD;
&#xD;
          -  Known rib or thoracic skeletal metastasis causing pain&#xD;
&#xD;
          -  Concern for active pleural infection&#xD;
&#xD;
          -  Respiratory failure&#xD;
&#xD;
          -  Irreversible bleeding diathesis&#xD;
&#xD;
          -  Inability to provide care for indwelling tunneled pleural catheter&#xD;
&#xD;
          -  Significantly loculated pleural space precluding drainage of pleural space, for which&#xD;
             IPC alone will likely not offer symptomatic benefit&#xD;
&#xD;
          -  Estimated life expectancy of &lt; 30 days (however, active enrollment in hospice program&#xD;
             is not an exclusion criteria)&#xD;
&#xD;
          -  Inability to read/understand/write in the English language&#xD;
&#xD;
          -  Inability to follow-up for appointments/protocol&#xD;
&#xD;
          -  Subject has any clinical condition, diagnosis, or social circumstance that, in the&#xD;
             opinion of the investigator would mean participation in the study would be&#xD;
             contraindicated.&#xD;
&#xD;
          -  Enrollment in alternative pleural catheter trial that would preclude enrollment within&#xD;
             this trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lonny Yarmus, DO</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>IP Research</last_name>
    <phone>410-502-2533</phone>
    <email>IPresearch@jhmi.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Northwest Community Healthcare</name>
      <address>
        <city>Arlington Heights</city>
        <state>Illinois</state>
        <zip>60005</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Neeraj Desai, MD</last_name>
      <email>desai@chestcenter.com</email>
    </contact>
    <contact_backup>
      <last_name>Brittany Adams</last_name>
      <email>badams1@NCH.ORG</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lonny Yarmus</last_name>
      <phone>410-502-5224</phone>
      <email>lyarmus@jhmi.edu</email>
    </contact>
    <investigator>
      <last_name>Lonny Yarmus</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gerard Silvestri, MD</last_name>
      <phone>843-792-9200</phone>
      <email>silvestr@musc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fabien Maldonado, MD</last_name>
      <phone>615-936-8422</phone>
      <email>fabien.maldonado@vanderbilt.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Swedish Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christopher R. Gilbert, MD</last_name>
      <phone>206-215-6800</phone>
      <email>Christopher.Gilbert@swedish.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Oxford</name>
      <address>
        <city>Oxford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Najib M Rahman, FRCP DPhil</last_name>
      <phone>01865 225205</phone>
      <email>najib.rahman@ndm.ox.ac.uk</email>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>February 4, 2019</study_first_submitted>
  <study_first_submitted_qc>February 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 5, 2019</study_first_posted>
  <last_update_submitted>December 6, 2022</last_update_submitted>
  <last_update_submitted_qc>December 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2022</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>Pleural Effusion</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>De-identified individual study data will be used for analysis by lead PI and analyst. However, study is using REDCap database system with restrictions so that researchers only see individual data from their own site.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03831386
org study id: IRB00158671
nct id: NCT03831386
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Malignant pleural effusion remains a debilitating complication of end stage cancer, which can
      be greatly improved by the introduction of the indwelling tunneled pleural catheter (IPC).
      However, there is no standard of care regarding drainage and limited data on the utility of
      different drainage techniques. In addition, many patients develop discomfort and chest pain
      during drainage. The investigators propose to evaluate gravity drainage and suction drainage
      on quality of life measures and outcomes.
Indwelling tunneled pleural catheters (IPCs) are used to alleviate pleural effusion as a
      first-line therapeutic (albeit palliative) intervention. Limited data currently exists on
      drainage techniques and the impact the techniques may have on quality of life. Current
      recommendations for IPC drainage range from daily drainage to once a week drainage, as well
      as only when needed for dyspnea. It has been theorized that active drainage of effusions may
      have an impact on the development of chest discomfort/pain, whereas passive regimens may
      allow for more gradual intrathoracic pleural changes and potentially offer a difference in
      drainage discomfort.

      The objective of this investigation is to compare different drainage strategies of indwelling
      pleural catheters (IPCs) regarding patient quality of life and outcomes. Patients will
      undergo placement of a pleural catheter as per standard institutional protocol. Patients will
      be randomized on a 1:1 basis into the suction drainage (active) arm or the gravity drainage
      (passive) arm. Patients will receive follow-up at two weeks, four weeks, twelve weeks and
      then as needed post IPC placement per standard clinical protocol. All patients will be asked
      to fill out quality of life questionnaires and update drainage diary information with
      patient's providers.

      Patients will undergo standard care treatment throughout the disease course and no different
      interventions regarding the pleural disease will be performed as a result of enrollment
      within this study. Study interventions/procedures will consist of questionnaires and patient
      self-reported documentation regarding patient's care and outcomes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in chest pain as assessed by Visual Analog Scale (VAS)
time frame: Daily, up to 2 weeks
description: The primary endpoint is the difference between the mean daily change in pain score during IPC drainage via the vacuum bottle technique and IPC drainage via the gravity bag technique over two weeks after IPC placement. Pre-drainage and post-drainage pain scores will be recorded each day of IPC placement. Measurements are in millimeters along a 10 cm VAS. VAS score is a range of 0 to 100. Lower limit is 0, meaning no pain; upper limit is 100, meaning extreme pain.
measure: Change in mean difference in chest pain as assessed by VAS
time frame: pre-IPC placement, 12 weeks post IPC placement or time of pleurodesis
description: This secondary endpoint is the difference between the change in pain scores via vacuum bottle vs. gravity bag pre-IPC placement to the last available score after IPC placement. This last available score would be at 12 weeks or time of pleurodesis. Measurements are in millimeters along a 10 cm Visual Analog Scale (VAS). VAS score is a range of 0 to 100. Lower limit is 0, meaning no pain; upper limit is 100, meaning extreme pain.
measure: Change in SF 36-Item Health Survey score
time frame: pre-IPC placement, 12 weeks post IPC placement or time of pleurodesis
description: This secondary endpoint is the difference between SF 36-Item Health Survey 1.0 scores via vacuum bottle vs. gravity bag from pre-IPC drainage to last available score after IPC placement (at 12 weeks or time of pleurodesis). Scoring is a 2-step process in which the numerical response from the Survey is first converted into a 0-100 scale (0 as lowest and 100 as highest possible score) using a conversion table by SF developers. These new values would be averaged according to their group identified in a second conversion table.
measure: Change in Functional Assessment of Chronic Illness Therapy (FACIT)-Dyspnea survey score
time frame: pre-IPC placement, 12 weeks post IPC placement or time of pleurodesis
description: This secondary endpoint is the difference between FACIT-Dyspnea scores via vacuum bottle vs. gravity bag from pre-IPC drainage to the last available score after IPC placement (at 12 weeks or time of pleurodesis). Individual responses are converted into scores, then summed for an overall score. Scores range from 0 (lower limit) to 30 (high limit); the higher the score, the worse the dyspnea.
arm group label: Vacuum
arm group type: Active Comparator
description: The pleural fluid will be drained by the syringe system with a one-way valve tubing system provided in the kit. Selection of the vacuum pressure will be at the discretion of the proceduralist, as per standard of care. Participants in this arm will undergo Vacuum-Based IPC.
arm group label: Gravity
arm group type: Experimental
description: The pleural fluid will be drained using gravity drainage to a bag positioned at bedside. Participants in this arm will undergo Gravity-Based IPC.
intervention type: Procedure
intervention name: Vacuum-Based IPC
description: An indwelling pleural catheter is placed inside the chest cavity to drain fluid from around the lungs. One end remains inside the body while the other drains via suction.
arm group label: Vacuum
intervention type: Procedure
intervention name: Gravity-Based IPC
description: An indwelling pleural catheter is placed inside the chest cavity to drain fluid from around the lungs. One end remains inside the body while the other drains via gravity.
arm group label: Gravity
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lonny Yarmus, DO
role: Principal Investigator
affiliation: Johns Hopkins University
last name: IP Research
phone: 410-502-2533
email: IPresearch@jhmi.edu
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Pleural Effusion
sharing ipd: No
ipd description: De-identified individual study data will be used for analysis by lead PI and analyst. However, study is using REDCap database system with restrictions so that researchers only see individual data from their own site.