<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/NCT04420481</url>
  </required_header>
  <id_info>
    <org_study_id>Protocol 2003-03-26</org_study_id>
    <nct_id>NCT04420481</nct_id>
  </id_info>
  <brief_title>Growth Hormone in Ischemic Heart Failure</brief_title>
  <official_title>Growth Hormone Treatment in Patients With Ischemic Heart Failure and Circulating Levels of NT-proBNP</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Göteborg University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Göteborg University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      In a double-blind, placebo-controlled trial, we randomly assigned 37 patients (mean age 66&#xD;
      years; 95% male) with ischemic heart failure (HF) (ejection fraction (EF) &lt; 40%) to a 9-month&#xD;
      treatment with either recombinant human GH (1.4 mg every other day) or placebo, with&#xD;
      subsequent 3-month treatment-free follow-up. The primary outcome was change in left&#xD;
      ventricular (LV) end-systolic volume measured by cardiac magnetic resonance (CMR). Secondary&#xD;
      outcomes comprised changes in cardiac structure and EF. Prespecified tertiary outcomes&#xD;
      included changes in New York Heat Association (NYHA) functional class and quality of life&#xD;
      (QoL), as well as levels of insulin-like growth factor-1 (IGF-1) and N-terminal pro-brain&#xD;
      natriuretic peptide (NT-proBNP).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      TITLE: GROWTH HORMONE IN HEART FAILURE Addition of recombinant human growth hormone to&#xD;
      standard heart failure therapy in patients with congestive heart failure due to ischaemic&#xD;
      heart disease.&#xD;
&#xD;
      A 12 month study, consisting of a 9 month double-blind, placebo-controlled randomised growth&#xD;
      hormone treatment phase followed by a 3 month growth hormone treatment-free period.&#xD;
&#xD;
      STUDY PHASE: III&#xD;
&#xD;
      COORDINATING CENTRE:&#xD;
&#xD;
      Endocrine Cardiac Unit (ECU) Sahlgrenska University Hospital, Sahlgrenska S-413 45 Göteborg&#xD;
      Sweden&#xD;
&#xD;
      STUDY PRODUCT:&#xD;
&#xD;
      Somatropin, recombinant human growth hormone (rhGH), Saizen® 8 mg (24 IE).&#xD;
&#xD;
      CONTROL PRODUCT:&#xD;
&#xD;
      Placebo for Saizen®&#xD;
&#xD;
      DOSAGE OF STUDY PRODUCT:&#xD;
&#xD;
      1,4 mg (4,2 IE) every other day.&#xD;
&#xD;
      DOSAGE:&#xD;
&#xD;
      9 month treatment period and a 3 month follow-up period. ROUTE OF ADMINISTRATION One&#xD;
      subcutaneous injection of Saizen® of study product, or corresponding placebo in the thigh or&#xD;
      abdomen given in the evening given every other day.&#xD;
&#xD;
      STUDY DESIGN:&#xD;
&#xD;
      Double-blind (regarding treatment), parallel, placebo-controlled, randomised.&#xD;
&#xD;
      STUDY POPULATION:&#xD;
&#xD;
      Female and male patients 75 years of age or below with congestive heart failure (NYHA class&#xD;
      II or III) due to ischemic heart disease.&#xD;
&#xD;
      NUMBER OF PATIENTs:&#xD;
&#xD;
      54 evaluable patients. MULTICENTRE: Yes. NUMBER OF CENTRES: Four&#xD;
&#xD;
      ALLOCATION OF TREATMENT:&#xD;
&#xD;
      Randomisation to treatment if all inclusion/exclusion criteria are met.&#xD;
&#xD;
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      To investigate the effect of subcutaneously administered Saizen® compared with placebo on&#xD;
      left ventricular endsystolic volume by MRI in patients with congestive heart failure due to&#xD;
      ischaemic heart disease.&#xD;
&#xD;
      SECONDARY OBJECTIVE:&#xD;
&#xD;
      To determine the effect of Saizen® on enddiastolic volume, left ventricular mass and left&#xD;
      ventricular ejection fraction&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      To determine the effect of Saizen® on change in NYHA class after 9 months of follow up.&#xD;
&#xD;
      To determine the effect of Saizen® on circulating levels of IGF-I and IGFBP-3 and to evaluate&#xD;
      the correlation between changes in IGF-I and the respective changes in left ventricular&#xD;
      ejection fraction, wall stress and left ventricular mass.&#xD;
&#xD;
      To evaluate the effect of Saizen® on quality of life by using two different questionnaires&#xD;
      (Minnesota - Living with Heart Failure and Cardiac Health Profile).&#xD;
&#xD;
      To determine the effect of Saizen® on neurohormonal activation by measuring NT-proBNP&#xD;
&#xD;
      SAFETY VARIABLES:&#xD;
&#xD;
      Hospitalization, morbidity and mortality.&#xD;
&#xD;
        -  Clinical events, including tendency to fluid retention, glucose intolerance, arrhythmias&#xD;
           and worsening heart failure.&#xD;
&#xD;
        -  Electrolytes, haematology, prothrombin complex, parameters for renal and hepatic&#xD;
           function.&#xD;
&#xD;
      ADVERSE EVENTS:&#xD;
&#xD;
      Spontaneously reported from patients and asked for. To be recorded in Case Report Forms&#xD;
      (CRFs) and on separate Adverse Event form if serious Adverse Event.&#xD;
&#xD;
      STATISTICS AND DATABASE MANAGEMENT:&#xD;
&#xD;
      Data management will be performed by Scandinavian Contract Research Institute and when clean&#xD;
      file is declared data will be made available to the statistician for the analysis. The&#xD;
      analysis will be performed according to the intention to treat principle.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 28, 2004</start_date>
  <completion_date type="Actual">February 25, 2012</completion_date>
  <primary_completion_date type="Actual">February 25, 2012</primary_completion_date>
  <phase>Phase 3</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>A 12 month study, consisting of a 9 months' double-blind, placebo-controlled randomised growth hormone treatment phase followed by a 3 months' growth hormone treatment-free period.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>All care providers and patients were masked with respect to the study drug during the study</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in left ventricular endsystolic volume</measure>
    <time_frame>9 months</time_frame>
    <description>Measured by CMR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in enddiastolic volume</measure>
    <time_frame>9 months</time_frame>
    <description>Measured by CMR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in left ventricular mass</measure>
    <time_frame>9 months</time_frame>
    <description>Measured by CMR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in left ventricular ejection fraction</measure>
    <time_frame>9 months</time_frame>
    <description>Measured by CMR</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in QoL Questionnaire</measure>
    <time_frame>9 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in NT-proBNP level</measure>
    <time_frame>9 months</time_frame>
    <description>blood sample</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Heart Failure, Systolic</condition>
  <condition>Ischemic Heart Disease Chronic</condition>
  <arm_group>
    <arm_group_label>Growth hormon group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A 12 month study, consisting of a 9 months growth hormone treatment phase followed by a 3 month growth hormone treatment-free period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A 12 month study, consisting of a 9 month placebo treatment phase followed by a 3 month treatment-free period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Somatropin</intervention_name>
    <description>Dose: 1,4 mg (4,2 IE) every other day Dosage: 9 month treatment period and a 3 month follow-up period Administration: One subcutaneous injection of somatropin or corresponding placebo in the thigh or abdomen given in the evening given every other day.</description>
    <arm_group_label>Growth hormon group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ejection fraction at rest less than 40% at the screening visit as measured by&#xD;
             echocardiography and a left ventricular enddiastolic diameter &gt; 32 mm/m2&#xD;
&#xD;
          -  Stable, optimised therapy for heart failure for at least 4 weeks prior to&#xD;
             randomisation including Angiotensin converting enzyme inhibitors, or if not tolerated,&#xD;
             angiotensin II blockers and/or digitalis. If tolerated patients should receive&#xD;
             beta-blockers for heart failure provided they have had a stable dose for at least 3&#xD;
             months prior to randomisation. The dose of diuretics may vary within a given&#xD;
             dose-range considered normal for that patient as determined by the investigator.&#xD;
&#xD;
          -  Written informed consent obtained&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled hypertension, treated or not treated with a diastolic blood pressure &gt;105&#xD;
             mm Hg&#xD;
&#xD;
          -  Haemodynamic clinically significant primary valvular disease or significant congenital&#xD;
             heart disease&#xD;
&#xD;
          -  Hypertrophic or idiopathic dilated cardiomyopathy&#xD;
&#xD;
          -  Acute pericarditis/myocarditis&#xD;
&#xD;
          -  Echocardiography findings such as mobile thrombus, significant pericardial effusion&#xD;
             and significant left ventricular aneurysm&#xD;
&#xD;
          -  Symptomatic or sustained ventricular arrhythmias within the last 3 months not&#xD;
             adequately treated with antiarrhythmic drugs or internal cardiovertor defibrillator&#xD;
             (ICD)&#xD;
&#xD;
          -  Unstable angina pectoris, or myocardial infarction within last 3 months&#xD;
&#xD;
          -  percutaneous coronary intervention performed within 6 months prior to randomization&#xD;
&#xD;
          -  Planned percutaneous coronary intervention, heart transplantation, other cardiac&#xD;
             surgery or other major surgery&#xD;
&#xD;
          -  Atrial fibrillation, if a frequency &gt; 100/min or a large frequency variation,&#xD;
             according to clinical judgment&#xD;
&#xD;
          -  Diabetes mellitus, insulin treated&#xD;
&#xD;
          -  Severe liver disease (alanine aminotransferase and/or alanine aminotransferase three&#xD;
             times upper limit of normal range laboratory values)&#xD;
&#xD;
          -  Severely reduced renal function (S-Creatinine above 250 micromol/l) or suspected&#xD;
             significant renal artery stenosis&#xD;
&#xD;
          -  Uncontrolled endocrine disorders&#xD;
&#xD;
          -  Ongoing treatment with calcium antagonist&#xD;
&#xD;
          -  Pregnancy or lactation or females of childbearing potential taking inadequate measures&#xD;
             to prevent pregnancy&#xD;
&#xD;
          -  History of or ongoing malignant disease&#xD;
&#xD;
          -  Previous treatment with growth hormone&#xD;
&#xD;
          -  Patients in a catabolic state&#xD;
&#xD;
          -  Known drug and/or alcohol abuse&#xD;
&#xD;
          -  Inability to cooperate or administer the study drug&#xD;
&#xD;
          -  Patients participating in any other clinical study, within 30 days prior to screening&#xD;
             visit and/or during this particular study period&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 5, 2020</last_update_submitted>
  <last_update_submitted_qc>June 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Heart Failure, Systolic</keyword>
  <keyword>Ischemic Heart Disease</keyword>
  <keyword>Growth Hormone Treatment</keyword>
  <keyword>Insulin Growth Factor I Resistance</keyword>
  <keyword>Hormone Disturbance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Heart Failure, Systolic</mesh_term>
    <mesh_term>Ischemia</mesh_term>
    <mesh_term>Systolic Murmurs</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data will be share upon reasonable request</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>3 months</ipd_time_frame>
    <ipd_access_criteria>A researcher that can show previous scientific merits that can be validated</ipd_access_criteria>
  </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/NCT04420481
org study id: Protocol 2003-03-26
nct id: NCT04420481
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
In a double-blind, placebo-controlled trial, we randomly assigned 37 patients (mean age 66
      years; 95% male) with ischemic heart failure (HF) (ejection fraction (EF) < 40%) to a 9-month
      treatment with either recombinant human GH (1.4 mg every other day) or placebo, with
      subsequent 3-month treatment-free follow-up. The primary outcome was change in left
      ventricular (LV) end-systolic volume measured by cardiac magnetic resonance (CMR). Secondary
      outcomes comprised changes in cardiac structure and EF. Prespecified tertiary outcomes
      included changes in New York Heat Association (NYHA) functional class and quality of life
      (QoL), as well as levels of insulin-like growth factor-1 (IGF-1) and N-terminal pro-brain
      natriuretic peptide (NT-proBNP).
TITLE: GROWTH HORMONE IN HEART FAILURE Addition of recombinant human growth hormone to
      standard heart failure therapy in patients with congestive heart failure due to ischaemic
      heart disease.

      A 12 month study, consisting of a 9 month double-blind, placebo-controlled randomised growth
      hormone treatment phase followed by a 3 month growth hormone treatment-free period.

      STUDY PHASE: III

      COORDINATING CENTRE:

      Endocrine Cardiac Unit (ECU) Sahlgrenska University Hospital, Sahlgrenska S-413 45 Göteborg
      Sweden

      STUDY PRODUCT:

      Somatropin, recombinant human growth hormone (rhGH), Saizen® 8 mg (24 IE).

      CONTROL PRODUCT:

      Placebo for Saizen®

      DOSAGE OF STUDY PRODUCT:

      1,4 mg (4,2 IE) every other day.

      DOSAGE:

      9 month treatment period and a 3 month follow-up period. ROUTE OF ADMINISTRATION One
      subcutaneous injection of Saizen® of study product, or corresponding placebo in the thigh or
      abdomen given in the evening given every other day.

      STUDY DESIGN:

      Double-blind (regarding treatment), parallel, placebo-controlled, randomised.

      STUDY POPULATION:

      Female and male patients 75 years of age or below with congestive heart failure (NYHA class
      II or III) due to ischemic heart disease.

      NUMBER OF PATIENTs:

      54 evaluable patients. MULTICENTRE: Yes. NUMBER OF CENTRES: Four

      ALLOCATION OF TREATMENT:

      Randomisation to treatment if all inclusion/exclusion criteria are met.

      PRIMARY OBJECTIVE:

      To investigate the effect of subcutaneously administered Saizen® compared with placebo on
      left ventricular endsystolic volume by MRI in patients with congestive heart failure due to
      ischaemic heart disease.

      SECONDARY OBJECTIVE:

      To determine the effect of Saizen® on enddiastolic volume, left ventricular mass and left
      ventricular ejection fraction

      TERTIARY OBJECTIVES:

      To determine the effect of Saizen® on change in NYHA class after 9 months of follow up.

      To determine the effect of Saizen® on circulating levels of IGF-I and IGFBP-3 and to evaluate
      the correlation between changes in IGF-I and the respective changes in left ventricular
      ejection fraction, wall stress and left ventricular mass.

      To evaluate the effect of Saizen® on quality of life by using two different questionnaires
      (Minnesota - Living with Heart Failure and Cardiac Health Profile).

      To determine the effect of Saizen® on neurohormonal activation by measuring NT-proBNP

      SAFETY VARIABLES:

      Hospitalization, morbidity and mortality.

        -  Clinical events, including tendency to fluid retention, glucose intolerance, arrhythmias
           and worsening heart failure.

        -  Electrolytes, haematology, prothrombin complex, parameters for renal and hepatic
           function.

      ADVERSE EVENTS:

      Spontaneously reported from patients and asked for. To be recorded in Case Report Forms
      (CRFs) and on separate Adverse Event form if serious Adverse Event.

      STATISTICS AND DATABASE MANAGEMENT:

      Data management will be performed by Scandinavian Contract Research Institute and when clean
      file is declared data will be made available to the statistician for the analysis. The
      analysis will be performed according to the intention to treat principle.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A 12 month study, consisting of a 9 months' double-blind, placebo-controlled randomised growth hormone treatment phase followed by a 3 months' growth hormone treatment-free period.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: All care providers and patients were masked with respect to the study drug during the study
measure: Change in left ventricular endsystolic volume
time frame: 9 months
description: Measured by CMR
measure: Change in enddiastolic volume
time frame: 9 months
description: Measured by CMR
measure: Change in left ventricular mass
time frame: 9 months
description: Measured by CMR
measure: Change in left ventricular ejection fraction
time frame: 9 months
description: Measured by CMR
measure: Change in QoL Questionnaire
time frame: 9 months
measure: Change in NT-proBNP level
time frame: 9 months
description: blood sample
arm group label: Growth hormon group
arm group type: Active Comparator
description: A 12 month study, consisting of a 9 months growth hormone treatment phase followed by a 3 month growth hormone treatment-free period.
arm group label: Control group
arm group type: Placebo Comparator
description: A 12 month study, consisting of a 9 month placebo treatment phase followed by a 3 month treatment-free period.
intervention type: Drug
intervention name: Somatropin
description: Dose: 1,4 mg (4,2 IE) every other day Dosage: 9 month treatment period and a 3 month follow-up period Administration: One subcutaneous injection of somatropin or corresponding placebo in the thigh or abdomen given in the evening given every other day.
arm group label: Growth hormon group
intervention type: Drug
intervention name: Placebo
description: Placebo
arm group label: Control group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Heart Diseases
mesh term: Myocardial Ischemia
mesh term: Coronary Artery Disease
mesh term: Heart Failure, Systolic
mesh term: Ischemia
mesh term: Systolic Murmurs
sharing ipd: Yes
ipd description: Data will be share upon reasonable request
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: 3 months
ipd access criteria: A researcher that can show previous scientific merits that can be validated