xml: <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/NCT05977933</url>
    </required_header>
    <id_info>
      <org_study_id>SHP0422</org_study_id>
      <secondary_id>R44HL162169</secondary_id>
      <nct_id>NCT05977933</nct_id>
    </id_info>
    <brief_title>Assessing the Utility of Submaximal CPET in Treatment Management of PAH</brief_title>
    <official_title>Assessing the Utility of Shape Submaximal Cardiopulmonary Exercise Testing in Detecting, Diagnosis and Treatment Management of Pulmonary Arterial Hypertension.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shape Medical Systems, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>Shape Medical Systems, Inc.</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
      <is_unapproved_device>Yes</is_unapproved_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Pulmonary hypertension (PH) is associated with worsening breathlessness and exercise&#xD;
        capacity, right-heart failure, and adverse outcomes including increased mortality. Moreover,&#xD;
        PH disease progression can be rapid; pharmaceutical intervention in early-stage Pulmonary&#xD;
        Hypertension (PH) can improve symptoms and functional capacity, and delayed diagnosis and&#xD;
        treatment of Pulmonary Hypertension (PH) likely reduces survival.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Pulmonary hypertension (PH) is a devastating disease characterized by progressive&#xD;
        dyspnea/exercise intolerance, right-heart failure, and carries a high risk of morbidity and&#xD;
        early mortality. PH disease progression can be rapid, and any delay in the diagnosis and&#xD;
        treatment of PH likely reduces survival. Given its clinical and prognostic significance,&#xD;
        early and accurate diagnosis of PH to allow prompt and optimal establishment of clinical care&#xD;
        is of critical importance. While traditional maximal/comprehensive cardiopulmonary exercise&#xD;
        testing (CPET) has been validated in PH, it has limitations that have hindered its&#xD;
        applicability to routine clinical assessment and monitoring. Our preliminary data suggest&#xD;
        that the signature ventilatory and pulmonary gas exchange derangements of PH become apparent&#xD;
        during even submaximal exercise. Our comprehensive proof-of-concept study (133 patients)&#xD;
        supports our hypothesis that the addition of pulmonary gas exchange responses to a&#xD;
        standardized 3-minute submaximal exercise test (Shape CPET) to standard echocardiographic&#xD;
        evidence of PH (i.e Right ventricular systolic pressure( RVSP) &gt;50 mmHg, suspicion of Right&#xD;
        ventricular (RV) dysfunction) improves the sensitivity for PH detection by almost 40%. The&#xD;
        Shape CPET system is compact and utilizes pattern-recognition software that automates&#xD;
        interpretation, making the system ideally suitable for widespread adoption. The overarching&#xD;
        objective of this small business innovation research (SBIR) proposal is to categorically&#xD;
        establish the Shape CPET as a tool that: 1) improves early detection of PH; and 2) provides&#xD;
        an objective evidence-based measure of PH therapy efficacy that can be easily used in&#xD;
        academic and community practices. Investigators have established a 10-center consortium of&#xD;
        academic and community PH centers for this SBIR proposal. Specific Aim 1 will assess the&#xD;
        clinical utility of submaximal cardiopulmonary exercise testing as a complementary tool for&#xD;
        the identification of pulmonary hypertension. Specific Aim 2 will assess whether&#xD;
        pharmacotherapy-induced improvements in pulmonary hypertension severity and disease status&#xD;
        are reflected in the physiological responses to a standardized submaximal cardiopulmonary&#xD;
        exercise test. The investigators hypothesize that the Shape CPET will prove to be an&#xD;
        efficacious adjunct to traditional clinical metrics to track changes in pulmonary vascular&#xD;
        function over time and responses to therapy aimed at alleviating PAH.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 1, 2023</start_date>
    <completion_date type="Anticipated">December 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Demonstrate the Submaximal Cardiopulmonary exercise testing (Shape CPET) is an effective complementary tool in the resting echocardiogram for detection of Pulmonary Hypertension.</measure>
      <time_frame>10-12 months</time_frame>
      <description>Identify Shape(CPET) gas exchange metrics, alone and in combination with echocardiographic (ECHO) measures to test for a correlation with Right heart catheterization (RHC) derived diagnostic determinations using standard uni- and multivariate analytic tools correlations with ECHO area under the curve (AUC) of receiver operating character (ROC) curves of Shape CPET+ ECHO vs those of Echo only screening will be used to examine if combining Shape with ECHO can improve the Echo only screening tool.&#xD;
  Identify variants of the fuzzy random forest walk algorithm. This approach, patients are divided into two groups: a training and test set. The algorithm creates &quot;leaves&quot; of unique variable combinations that &quot;bag&quot; all patients in the training set into categories of classification (pulmonary arterial hypertension). The combinatorial routine that best leads to the classification in the training set is applied to the testing set whose results are compared to the reference standard.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Demonstrate the percent change in submaximal Shape Cardiopulmonary exercise testing (Shape CPET) metrics and the 6 minute walk time distance (6MWTd)</measure>
      <time_frame>3 months and 6 months</time_frame>
      <description>Identify the percent changes in the Shape variables and 6-minute walk time distance (6MWTd) from baseline to first post treatment (90 days) and to second post treatment (180 days) will be averaged and compared statistically using two-way, paired &quot;t&quot; tests with a significance level set at p&lt;.05.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>The correlation of select non-invasive Shape Cardiopulmonary exercise test (CPET) metric to invasive hemodynamic variables</measure>
      <time_frame>10-12 months</time_frame>
      <description>Correlation of the Shape cardiopulmonary exercise test (CPET) variables with right heart catheterization (RHC) derived diagnostic determinations using standard uni- and multivariate analytic tools correlations with echocardiogram area under the curve (AUC) of receiver operating characteristics (ROC) curves of Shape CPET + Echocardiograph (Echo) vs those of Echo only screening will be used to examine if combining Shape with echocardiography can improve the Echo only screening tool</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assessment of Pharmacotherapy-induced improvement or sensitivity of changes in pulmonary hypertension severity and disease status</measure>
      <time_frame>3 months and 6 months</time_frame>
      <description>Identify changes from baseline to subsequent visits in values of Shape CPET variable in the physiological responses to a PAH functional class, 6MWTd and time to clinical worsening (TTCW). The TTCW or the &quot;time to clinical worsening&quot; is based upon 1) an increase in functional capacitance (FC); 2) a 15 % decrease in 6-minute walk test distance (6MWTd) 3) hospitalization in days 4) death in days.</description>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">550</enrollment>
    <condition>Pulmonary Arterial Hypertension</condition>
    <arm_group>
      <arm_group_label>PAH Patients</arm_group_label>
      <description>Pulmonary hypertension (PH) is associated with worsening breathlessness and exercise capacity, right-heart failure, and adverse outcomes including increased mortality. Moreover, PH disease progression can be rapid; pharmaceutical intervention in early-stage PH can improve symptoms and functional capacity, and delayed diagnosis and treatment of PH likely reduces survival.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Shape II CPET</intervention_name>
      <description>Submaximal Cardiopulmonary exercise test equipment</description>
      <arm_group_label>PAH Patients</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          The population will be consenting legal adults (minimum age 21 and no limit on maximum age)&#xD;
          unless imposed by individual site standard of care (SoC). with no contraindications to&#xD;
          exercise testing will be recruited. Suspected of pulmonary hypertension PH.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria Study Aim 1:&#xD;
  &#xD;
            -  Subject referred for clinical assessment due to unexplained or worsening dyspnea&#xD;
               and/or suspected Pulmonary Hypertension (PH).&#xD;
  &#xD;
            -  Subject is able and willing to provide appropriate Informed consent.&#xD;
  &#xD;
            -  Subject is greater than or equal to 21 years old&#xD;
  &#xD;
            -  Subject is not dependent on supplemental O2 to allow for CPET/sub-max-Shape exercise&#xD;
               testing&#xD;
  &#xD;
            -  Subject is capable of performing a sub-max, incremental step exercise protocol, both&#xD;
               physically and mentally, with no absolute contraindications to exercise testing, such&#xD;
               as those causing symptoms or hemodynamic compromise Contraindications include syncope,&#xD;
               active endocarditis, myocarditis or pericarditis, symptomatic severe aortic stenosis,&#xD;
               uncontrolled heart failure (HF), uncontrolled cardiac arrhythmia, acute pulmonary&#xD;
               embolus or pulmonary infarction, thrombosis of lower extremities, suspected dissecting&#xD;
               aneurysm, uncontrolled asthma, pulmonary edema, respiratory failure, acute&#xD;
               non-pulmonary disorder that may affect exercise performance or be aggravated by&#xD;
               exercise such as infarction, renal failure or thyrotoxicosis, medical impairment with&#xD;
               inability to cooperate with protocol instructions&#xD;
  &#xD;
          Inclusion Criteria Study Aim 2:&#xD;
  &#xD;
            -  Subject must have been enrolled in Study Aim 1&#xD;
  &#xD;
            -  Dyspnea subject who has undergone echo examination and presented with suspicion of&#xD;
               pulmonary arterial hypertension (PAH) category world health organization (WHO) I (mean&#xD;
               pulmonary artery pressure (PAP) ≥ 20 mmHg; pulmonary vascular resistance (PVR) &gt; 2 WU&#xD;
               and pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg&#xD;
  &#xD;
          Exclusion Criteria Study Aim 1:&#xD;
  &#xD;
            -  Resting Hypoxemia (oxygen saturation (Sp02) &lt;85%)&#xD;
  &#xD;
            -  The subject's mean arterial blood pressure is less than 70 mmHg despite fluid&#xD;
               resuscitation and pressor therapy.&#xD;
  &#xD;
            -  The subject has positive pregnancy test (verified in a manner consistent with&#xD;
               institution's standard of care)&#xD;
  &#xD;
            -  The subject has joint limitations to performing incremental exercise with gas exchange&#xD;
               monitoring.&#xD;
  &#xD;
          Exclusion Criteria Study Aim 2:&#xD;
  &#xD;
            -  Normal pulmonary hemodynamics on right heart Catheterization (RHC) ( mean pulmonary&#xD;
               arterial pressure (mPAP) ≤ 20mmHG)&#xD;
  &#xD;
            -  RHC evidence of precapillary PH (mPAP &gt;20 mmHg, PAWP ≤15 mmHg, PVR &gt;2 WU) but has a&#xD;
               diagnosis of group III, IV or V PH&#xD;
  &#xD;
            -  RHC evidence isolated postcapillary PH (mPAP &gt;20 mmHg, PAWP &gt;15 mmHg, PVR ≤2 WU) or&#xD;
               combined pre- and postcapillary PH (mPAP &gt;20 mmHg, pulmonary arterial wedge pressure&#xD;
               (PAWP) &gt;15 mmHg, PVR &gt;2 WU)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>21 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Harbor-UCLA Medical Center</name>
        <address>
          <city>Torrance</city>
          <state>California</state>
          <zip>90502-2006</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Tatiana Gomes</last_name>
        <phone>310-222-3560</phone>
        <email>tatiana.gomes@lundquist.org</email>
      </contact>
      <investigator>
        <last_name>Ronald Oudiz, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>National Jewish Health</name>
        <address>
          <city>Denver</city>
          <state>Colorado</state>
          <zip>80206-2761</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Jami Henriksen</last_name>
        <phone>303-398-1096</phone>
        <email>henriksenj@NJhealth.org</email>
      </contact>
      <investigator>
        <last_name>Marjorie P George, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Mayo Clinic</name>
        <address>
          <city>Jacksonville</city>
          <state>Florida</state>
          <zip>32224-1865</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Taylor Galloway</last_name>
        <phone>904-953-0543</phone>
        <email>galloway.taylor@mayo.edu</email>
      </contact>
      <investigator>
        <last_name>Brian Taylor, Phd</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>WellStar Health System</name>
        <address>
          <city>Atlanta</city>
          <state>Georgia</state>
          <zip>30312-1213</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Brandon D Pickens</last_name>
        <phone>470-793-4046</phone>
        <email>brandon.pickens@wellstar.org</email>
      </contact>
      <investigator>
        <last_name>Paul Guichard, DO</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Southeastern Cardiology</name>
        <address>
          <city>Columbus</city>
          <state>Georgia</state>
          <zip>31904-7955</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Tanya Milton</last_name>
        <phone>706-243-4500</phone>
        <email>hchampion@southeasterncardiology.com</email>
      </contact>
      <investigator>
        <last_name>Hunter Champion, MD, Phd</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Weill Cornell Medicine</name>
        <address>
          <city>New York</city>
          <state>New York</state>
          <zip>10021-9800</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Dolores T Reynolds</last_name>
        <phone>646-962-5555</phone>
        <email>dtr2001@med.cornell.edu</email>
      </contact>
      <investigator>
        <last_name>Evelyn Horn, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>June 29, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</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>Pulmonary Arterial Hypertension</mesh_term>
      <mesh_term>Familial Primary Pulmonary Hypertension</mesh_term>
      <mesh_term>Hypertension</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05977933
  org study id: SHP0422
  secondary id: R44HL162169
  nct id: NCT05977933
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: Yes
  is unapproved device: Yes
  is us export: No
  Pulmonary hypertension (PH) is associated with worsening breathlessness and exercise
        capacity, right-heart failure, and adverse outcomes including increased mortality. Moreover,
        PH disease progression can be rapid; pharmaceutical intervention in early-stage Pulmonary
        Hypertension (PH) can improve symptoms and functional capacity, and delayed diagnosis and
        treatment of Pulmonary Hypertension (PH) likely reduces survival.
  Pulmonary hypertension (PH) is a devastating disease characterized by progressive
        dyspnea/exercise intolerance, right-heart failure, and carries a high risk of morbidity and
        early mortality. PH disease progression can be rapid, and any delay in the diagnosis and
        treatment of PH likely reduces survival. Given its clinical and prognostic significance,
        early and accurate diagnosis of PH to allow prompt and optimal establishment of clinical care
        is of critical importance. While traditional maximal/comprehensive cardiopulmonary exercise
        testing (CPET) has been validated in PH, it has limitations that have hindered its
        applicability to routine clinical assessment and monitoring. Our preliminary data suggest
        that the signature ventilatory and pulmonary gas exchange derangements of PH become apparent
        during even submaximal exercise. Our comprehensive proof-of-concept study (133 patients)
        supports our hypothesis that the addition of pulmonary gas exchange responses to a
        standardized 3-minute submaximal exercise test (Shape CPET) to standard echocardiographic
        evidence of PH (i.e Right ventricular systolic pressure( RVSP) >50 mmHg, suspicion of Right
        ventricular (RV) dysfunction) improves the sensitivity for PH detection by almost 40%. The
        Shape CPET system is compact and utilizes pattern-recognition software that automates
        interpretation, making the system ideally suitable for widespread adoption. The overarching
        objective of this small business innovation research (SBIR) proposal is to categorically
        establish the Shape CPET as a tool that: 1) improves early detection of PH; and 2) provides
        an objective evidence-based measure of PH therapy efficacy that can be easily used in
        academic and community practices. Investigators have established a 10-center consortium of
        academic and community PH centers for this SBIR proposal. Specific Aim 1 will assess the
        clinical utility of submaximal cardiopulmonary exercise testing as a complementary tool for
        the identification of pulmonary hypertension. Specific Aim 2 will assess whether
        pharmacotherapy-induced improvements in pulmonary hypertension severity and disease status
        are reflected in the physiological responses to a standardized submaximal cardiopulmonary
        exercise test. The investigators hypothesize that the Shape CPET will prove to be an
        efficacious adjunct to traditional clinical metrics to track changes in pulmonary vascular
        function over time and responses to therapy aimed at alleviating PAH.
  observational model: Cohort
  time perspective: Prospective
  measure: Demonstrate the Submaximal Cardiopulmonary exercise testing (Shape CPET) is an effective complementary tool in the resting echocardiogram for detection of Pulmonary Hypertension.
  time frame: 10-12 months
  description: Identify Shape(CPET) gas exchange metrics, alone and in combination with echocardiographic (ECHO) measures to test for a correlation with Right heart catheterization (RHC) derived diagnostic determinations using standard uni- and multivariate analytic tools correlations with ECHO area under the curve (AUC) of receiver operating character (ROC) curves of Shape CPET+ ECHO vs those of Echo only screening will be used to examine if combining Shape with ECHO can improve the Echo only screening tool.
  Identify variants of the fuzzy random forest walk algorithm. This approach, patients are divided into two groups: a training and test set. The algorithm creates "leaves" of unique variable combinations that "bag" all patients in the training set into categories of classification (pulmonary arterial hypertension). The combinatorial routine that best leads to the classification in the training set is applied to the testing set whose results are compared to the reference standard.
  measure: Demonstrate the percent change in submaximal Shape Cardiopulmonary exercise testing (Shape CPET) metrics and the 6 minute walk time distance (6MWTd)
  time frame: 3 months and 6 months
  description: Identify the percent changes in the Shape variables and 6-minute walk time distance (6MWTd) from baseline to first post treatment (90 days) and to second post treatment (180 days) will be averaged and compared statistically using two-way, paired "t" tests with a significance level set at p<.05.
  measure: The correlation of select non-invasive Shape Cardiopulmonary exercise test (CPET) metric to invasive hemodynamic variables
  time frame: 10-12 months
  description: Correlation of the Shape cardiopulmonary exercise test (CPET) variables with right heart catheterization (RHC) derived diagnostic determinations using standard uni- and multivariate analytic tools correlations with echocardiogram area under the curve (AUC) of receiver operating characteristics (ROC) curves of Shape CPET + Echocardiograph (Echo) vs those of Echo only screening will be used to examine if combining Shape with echocardiography can improve the Echo only screening tool
  measure: Assessment of Pharmacotherapy-induced improvement or sensitivity of changes in pulmonary hypertension severity and disease status
  time frame: 3 months and 6 months
  description: Identify changes from baseline to subsequent visits in values of Shape CPET variable in the physiological responses to a PAH functional class, 6MWTd and time to clinical worsening (TTCW). The TTCW or the "time to clinical worsening" is based upon 1) an increase in functional capacitance (FC); 2) a 15 % decrease in 6-minute walk test distance (6MWTd) 3) hospitalization in days 4) death in days.
  arm group label: PAH Patients
  description: Pulmonary hypertension (PH) is associated with worsening breathlessness and exercise capacity, right-heart failure, and adverse outcomes including increased mortality. Moreover, PH disease progression can be rapid; pharmaceutical intervention in early-stage PH can improve symptoms and functional capacity, and delayed diagnosis and treatment of PH likely reduces survival.
  intervention type: Device
  intervention name: Shape II CPET
  description: Submaximal Cardiopulmonary exercise test equipment
  arm group label: PAH Patients
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 21 Years
  maximum age: N/A
  healthy volunteers: No
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Pulmonary Arterial Hypertension
  mesh term: Familial Primary Pulmonary Hypertension
  mesh term: Hypertension
  sharing ipd: No