<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/NCT04475042</url>
  </required_header>
  <id_info>
    <org_study_id>19.185</org_study_id>
    <nct_id>NCT04475042</nct_id>
  </id_info>
  <brief_title>Stratified Treatment to Ameliorate Diastolic Left Ventricular Stiffness in Heart Failure With Preserved Ejection Fraction</brief_title>
  <acronym>STADIA-HFpEF</acronym>
  <official_title>Stratified Treatment to Ameliorate Diastolic Left Ventricular Stiffness in Heart Failure With Preserved Ejection Fraction. A 35-week, Single-center, Prospective, Double-blind, Controlled, Randomized, 2x2 Crossover, Interventional Phase II Study, Investigating the Effect of Treatment With Dapagliflozin 10mg od on Left Ventricular Distensibility in Patients With Early HFpEF.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mariëlle Scheffer</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Onze Lieve Vrouwe Gasthuis</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      A 35-week, single-center, prospective, double-blind, controlled, randomized, 2x2 crossover,&#xD;
      interventional Phase II study, investigating the effect of treatment with dapagliflozin 10mg&#xD;
      od on Left Ventricular distensibility in patients with early HFpEF.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">May 2022</completion_date>
  <primary_completion_date type="Anticipated">November 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Left Ventricular (LV) e'</measure>
    <time_frame>13 weeks</time_frame>
    <description>echocardiographically measured</description>
  </primary_outcome>
  <primary_outcome>
    <measure>E/e'/LV end-diastolic volume index</measure>
    <time_frame>13 weeks</time_frame>
    <description>echocardiographically measured</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Kansas City Cardiomyopathy Questionnaire</measure>
    <time_frame>13 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6-minute walk test</measure>
    <time_frame>13 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left atrial volume</measure>
    <time_frame>13 weeks</time_frame>
    <description>Echocardiographically derived volume</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diastolic parameters</measure>
    <time_frame>13 weeks</time_frame>
    <description>Echocardiographically derived function, filling and compliance of Left Ventricular</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left atrial function</measure>
    <time_frame>13 weeks</time_frame>
    <description>Echocardiographically derived strain analysis, resevoir, conduit and booster pump function</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">26</enrollment>
  <condition>Heart Failure, Diastolic</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dapagliflozin - washout period - placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Placebo - washout period - Dapagliflozin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dapagliflozin</intervention_name>
    <description>10mg od</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years at time of screening&#xD;
&#xD;
          2. Symptomatic chronic heart failure patients with diagnosis of heart failure and:&#xD;
&#xD;
               -  NYHA class II-IV&#xD;
&#xD;
               -  Preserved systolic Left Ventricular (LV) function, defined by: LV Ejection&#xD;
                  Fraction (LVEF) ≥ 50% and LV end-diastolic volume index &lt;97 ml/m2&#xD;
&#xD;
               -  Evidence of diastolic LV dysfunction and at least 1 out of the 5 following&#xD;
                  additional criteria:&#xD;
&#xD;
                    1. H2FPEF score ≥ 6;&#xD;
&#xD;
                    2. HFA-PEFF score ≥ 5;&#xD;
&#xD;
                    3. Pulmonary capillary wedge pressure &gt; 15 mmHg at rest or &gt; 25 mmHg with&#xD;
                       exercise assessed with right heart catheterization;&#xD;
&#xD;
          3. Cardiac MRI T1 derived extracellular volume &lt;29% at screening&#xD;
&#xD;
          4. Oral diuretics, if prescribed to the patient according to local guidelines and at the&#xD;
             discretion of the investigator, should be stable for at least 1 week prior to baseline&#xD;
             visit&#xD;
&#xD;
          5. Signed and dated written informed consent in accordance with GCP and local legislation&#xD;
             prior to admission to the trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Reduced systolic LV function (LVEF &lt; 50%), measured at any time point in the history&#xD;
             of the patient&#xD;
&#xD;
          2. Obstructive coronary artery disease with evidence of ischemia&#xD;
&#xD;
          3. Myocardial infarction, coronary artery bypass graft surgery or other major&#xD;
             cardiovascular surgery, stroke or TIA in past 90 days prior to screening visit&#xD;
&#xD;
          4. More than mild valve stenosis&#xD;
&#xD;
          5. More than moderate aortic and/or mitral valve regurgitation&#xD;
&#xD;
          6. Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation&#xD;
             diseases (e.g. hemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy&#xD;
             with reversible causes (stress cardiomyopathy), hypertrophic (obstructive)&#xD;
             cardiomyopathy or known pericardial constriction&#xD;
&#xD;
          7. History of mitral valve repair or replacement&#xD;
&#xD;
          8. Atrial fibrillation or atrial flutter with a resting heart rate &gt; 110 bpm at screening&#xD;
&#xD;
          9. Acute decompensation that requires intravenous loop diuretics&#xD;
&#xD;
         10. Systolic blood pressure ≥ 180 mmHg. If SBP &gt; 150 mmHg and &lt; 180 mmHg, the patient&#xD;
             should be receiving at least 3 antihypertensive drugs at screening or baseline visit&#xD;
&#xD;
         11. Symptomatic hypotension and/or a SBP &lt; 100 mmHg at screening or baseline visit&#xD;
&#xD;
         12. Impaired renal function, defined as eGFR &lt; 30 ml/min/1.73 m2&#xD;
&#xD;
         13. Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT),&#xD;
             or alkaline phosphatase above 3x upper limit of normal or history of cirrhosis with&#xD;
             evidence of portal hypertension&#xD;
&#xD;
         14. Hemoglobin &lt; 9 g/dl at screening&#xD;
&#xD;
         15. Chronic obstructive pulmonary disease, more than GOLD class 2&#xD;
&#xD;
         16. Pulmonary function test with FEV1/FVC &lt; 80%&#xD;
&#xD;
         17. Primary pulmonary arterial hypertension&#xD;
&#xD;
         18. Type 1 Diabetes Mellitus&#xD;
&#xD;
         19. History of ketoacidosis&#xD;
&#xD;
         20. Any documented active or suspected malignancy or history of malignancy within 2 years&#xD;
             prior to screening, except appropriately treated basal cell carcinoma of the skin or&#xD;
             in situ carcinoma of uterine cervix or low risk prostate cancer (biopsy Gleason score&#xD;
             of ≤ 6 and clinical stage T1c or T2a)&#xD;
&#xD;
         21. Current use or prior use of a SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor&#xD;
             within 3 months prior to screening visit. Discontinuation of a SGLT-2 inhibitor or&#xD;
             combined SGLT-1 and 2 inhibitor for the purposes of study enrolment is not permitted&#xD;
&#xD;
         22. Pregnancy or lactation&#xD;
&#xD;
         23. Any (clinical) condition that, in the investigator's opinion, would jeopardize&#xD;
             patients safety while participating in this trial, or may prevent the patient from&#xD;
             adhering to the trial protocol&#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_contact>
    <last_name>Marielle Scheffer, MD</last_name>
    <phone>0031205994889</phone>
    <email>mailcardio.research@olvg.nl</email>
  </overall_contact>
  <location>
    <facility>
      <name>OLVG</name>
      <address>
        <city>Amsterdam</city>
        <state>Noord-Holland</state>
        <zip>1091</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marielle Scheffer</last_name>
      <phone>0031205994889</phone>
      <email>mailcardio.research@olvg.nl</email>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>September 18, 2020</last_update_submitted>
  <last_update_submitted_qc>September 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Onze Lieve Vrouwe Gasthuis</investigator_affiliation>
    <investigator_full_name>Mariëlle Scheffer</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Heart Failure, Diastolic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dapagliflozin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04475042
org study id: 19.185
nct id: NCT04475042
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A 35-week, single-center, prospective, double-blind, controlled, randomized, 2x2 crossover,
      interventional Phase II study, investigating the effect of treatment with dapagliflozin 10mg
      od on Left Ventricular distensibility in patients with early HFpEF.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Left Ventricular (LV) e'
time frame: 13 weeks
description: echocardiographically measured
measure: E/e'/LV end-diastolic volume index
time frame: 13 weeks
description: echocardiographically measured
measure: Kansas City Cardiomyopathy Questionnaire
time frame: 13 weeks
measure: 6-minute walk test
time frame: 13 weeks
measure: Left atrial volume
time frame: 13 weeks
description: Echocardiographically derived volume
measure: Diastolic parameters
time frame: 13 weeks
description: Echocardiographically derived function, filling and compliance of Left Ventricular
measure: Left atrial function
time frame: 13 weeks
description: Echocardiographically derived strain analysis, resevoir, conduit and booster pump function
arm group label: Group A
arm group type: Active Comparator
description: Dapagliflozin - washout period - placebo
arm group label: Group B
arm group type: Active Comparator
description: Placebo - washout period - Dapagliflozin
intervention type: Drug
intervention name: Dapagliflozin
description: 10mg od
arm group label: Group A
arm group label: Group B
intervention type: Drug
intervention name: Placebo
description: Placebo
arm group label: Group A
arm group label: Group B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marielle Scheffer, MD
phone: 0031205994889
email: mailcardio.research@olvg.nl
facility: 
status: Recruiting
contact: 
country: Netherlands
responsible party type: Sponsor-Investigator
investigator affiliation: Onze Lieve Vrouwe Gasthuis
investigator full name: Mariëlle Scheffer
investigator title: Principal Investigator
mesh term: Heart Failure
mesh term: Heart Failure, Diastolic
mesh term: Dapagliflozin