<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/NCT03300427</url>
  </required_header>
  <id_info>
    <org_study_id>CLCZ696BFI03</org_study_id>
    <secondary_id>2017-002113-64</secondary_id>
    <nct_id>NCT03300427</nct_id>
  </id_info>
  <brief_title>The Effects of Sacubitril/Valsartan on Cardiac Oxygen Consumption and Efficiency of Cardiac Work in Heart Failure Patients</brief_title>
  <acronym>TurkuPET</acronym>
  <official_title>Controlled Trial on the Short-term Effects of Sacubitril/Valsartan Therapy on Cardiac Oxygen Consumption and Efficiency of Cardiac Work in Patients With NYHA II-III Heart Failure and Reduced Systolic Function Using 11C-acetate Positron Emission Tomography and Echocardiography</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</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>
      The study will assess the effects of 6 weeks of stable sacubitril/valsartan therapy, as&#xD;
      compared with valsartan therapy, on cardiac oxygen consumption and the efficiency of cardiac&#xD;
      work in patients with NYHA II-III heart failure (HF) and reduced systolic function using&#xD;
      11C-acetate positron emission tomography (PET) and echocardiography.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 5, 2018</start_date>
  <completion_date type="Actual">March 23, 2022</completion_date>
  <primary_completion_date type="Actual">March 23, 2022</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in cardiac oxygen consumption and efficiency of cardiac work</measure>
    <time_frame>baseline, at week 6</time_frame>
    <description>Change from baseline in cardiac oxygen consumption and efficiency of cardiac work after 6 weeks of stable sacubitril/valsartan therapy compared to that of in patients on valsartan therapy using 11C-acetate positron emission tomography (PET).</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>sacubitril/valsartan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be randomized to two treatment arms in a 1:1, double blinded fashion. Two strengths of sacubitril/valsartan will be available for use after randomization, 49 mg sacubitril/51 mg valsartan and 97 mg sacubitril/103 mg valsartan. After randomization, subjects in this arm will receive sacubitril/valsartan 100 mg orally twice daily (BID). The dose will be then up-titrated to 200 mg BID (or maintained at the starting dose level, if up-titration is not possible). Dose modifications are allowed until week 4 after the randomization. In order to be eligible for the final assessments, the subject has to tolerate the 100 mg BID dose at the minimum. In total, participants will be on sacubitril/valsartan for a minimum of 8 weeks and a maximum of 10 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>valsartan</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will be randomized to two treatment arms in a 1:1, double blinded fashion. In this arm, Valsartan 80 mg and 160 mg will be used as comparative drug, taken orally BID at home. Depending on the screening/run-in dose the subjects in this arm will get either valsartan 80 mg BID or valsartan 160 mg BID. During the treatment period the dose of valsartan will be up-titrated to the highest tolerated dose (160 mg BID) or maintained at 80 mg BID if up-titration is not possible. Dose modifications are allowed until week 4 after the randomization. In order to be eligible for the final assessments, the subject has to tolerate at least 80 mg BID dose of valsartan. The treatment phase will be a minimum of 8 weeks, and a maximum of 10 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sacubitril/valsatran</intervention_name>
    <description>sacubitril/valsatran 100 or 200 mg BID</description>
    <arm_group_label>sacubitril/valsartan</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>valsartan</intervention_name>
    <description>Valsartan 80 or 160 mg BID</description>
    <arm_group_label>valsartan</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo to valsartan</intervention_name>
    <description>placebo to valsartan 80 or 160 BID</description>
    <arm_group_label>sacubitril/valsartan</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo to sacubitril/valsartan</intervention_name>
    <description>placebo to sacubitril/valsartan 100 or 200 mg BID</description>
    <arm_group_label>valsartan</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  40-80 years of age&#xD;
&#xD;
          -  Chronic HF with reduced EF (left ventricle EF 25-35%) and NYHA class II-III symptoms.&#xD;
&#xD;
          -  Systolic BP 110-160 mm Hg&#xD;
&#xD;
          -  Optimal standard HF therapy according to European Society of Cardiology (ESC)&#xD;
             guidelines at a stable dose for at least 4 weeks before the screening visit.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR) &lt; 45 ml/min&#xD;
&#xD;
          -  Serum potassium &gt; 5.2 mmol/l and creatinine &gt;1.5 x ULN&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Turku</city>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>September 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>September 27, 2022</last_update_submitted>
  <last_update_submitted_qc>September 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Heart failure with reduced left ventricular ejection fraction</keyword>
  <keyword>LVEF</keyword>
  <keyword>Cardiac dysfunction</keyword>
  <keyword>Heart muscle dysfunction</keyword>
  <keyword>Left ventricular (LV) dilation</keyword>
  <keyword>Left ventricular hypertrophy</keyword>
  <keyword>HF</keyword>
  <keyword>AHF</keyword>
  <keyword>CHF</keyword>
  <keyword>CCF</keyword>
  <keyword>acute heart failure</keyword>
  <keyword>chronic heart failure</keyword>
  <keyword>congestive heart failure</keyword>
  <keyword>congestive cardiac failure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Valsartan</mesh_term>
    <mesh_term>Sacubitril and valsartan sodium hydrate drug combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
  </patient_data>
  <pending_results>
    <submitted>March 20, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03300427
org study id: CLCZ696BFI03
secondary id: 2017-002113-64
nct id: NCT03300427
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study will assess the effects of 6 weeks of stable sacubitril/valsartan therapy, as
      compared with valsartan therapy, on cardiac oxygen consumption and the efficiency of cardiac
      work in patients with NYHA II-III heart failure (HF) and reduced systolic function using
      11C-acetate positron emission tomography (PET) and echocardiography.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from baseline in cardiac oxygen consumption and efficiency of cardiac work
time frame: baseline, at week 6
description: Change from baseline in cardiac oxygen consumption and efficiency of cardiac work after 6 weeks of stable sacubitril/valsartan therapy compared to that of in patients on valsartan therapy using 11C-acetate positron emission tomography (PET).
arm group label: sacubitril/valsartan
arm group type: Experimental
description: Participants will be randomized to two treatment arms in a 1:1, double blinded fashion. Two strengths of sacubitril/valsartan will be available for use after randomization, 49 mg sacubitril/51 mg valsartan and 97 mg sacubitril/103 mg valsartan. After randomization, subjects in this arm will receive sacubitril/valsartan 100 mg orally twice daily (BID). The dose will be then up-titrated to 200 mg BID (or maintained at the starting dose level, if up-titration is not possible). Dose modifications are allowed until week 4 after the randomization. In order to be eligible for the final assessments, the subject has to tolerate the 100 mg BID dose at the minimum. In total, participants will be on sacubitril/valsartan for a minimum of 8 weeks and a maximum of 10 weeks.
arm group label: valsartan
arm group type: Active Comparator
description: Participants will be randomized to two treatment arms in a 1:1, double blinded fashion. In this arm, Valsartan 80 mg and 160 mg will be used as comparative drug, taken orally BID at home. Depending on the screening/run-in dose the subjects in this arm will get either valsartan 80 mg BID or valsartan 160 mg BID. During the treatment period the dose of valsartan will be up-titrated to the highest tolerated dose (160 mg BID) or maintained at 80 mg BID if up-titration is not possible. Dose modifications are allowed until week 4 after the randomization. In order to be eligible for the final assessments, the subject has to tolerate at least 80 mg BID dose of valsartan. The treatment phase will be a minimum of 8 weeks, and a maximum of 10 weeks.
intervention type: Drug
intervention name: sacubitril/valsatran
description: sacubitril/valsatran 100 or 200 mg BID
arm group label: sacubitril/valsartan
intervention type: Drug
intervention name: valsartan
description: Valsartan 80 or 160 mg BID
arm group label: valsartan
intervention type: Drug
intervention name: placebo to valsartan
description: placebo to valsartan 80 or 160 BID
arm group label: sacubitril/valsartan
intervention type: Drug
intervention name: placebo to sacubitril/valsartan
description: placebo to sacubitril/valsartan 100 or 200 mg BID
arm group label: valsartan
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: Finland
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Valsartan
mesh term: Sacubitril and valsartan sodium hydrate drug combination
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
submitted: March 20, 2023