<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/NCT01699776</url>
  </required_header>
  <id_info>
    <org_study_id>CG&amp;PJ-Dig-Iva 2009-2012</org_study_id>
    <nct_id>NCT01699776</nct_id>
  </id_info>
  <brief_title>Efficacy Study of Digoxin &amp; Ivabradine to Treat Heart Failure</brief_title>
  <acronym>Dig&amp;Iva</acronym>
  <official_title>Comparison of Digoxin and Ivabradine in Heart Failure With Preserved Systolic Function. Time to Rethink About Digoxin.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cocco, Giuseppe, M.D.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cardiology Office, Rheinfelden, Switzerland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cocco, Giuseppe, M.D.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is established that at a serum concentration 0.5-0.9 ng/ml digoxin is effective in&#xD;
      patients with heart failure, especially in the presence of atrial fibrillation (AF). It is&#xD;
      the claimed that ivabradine by lowering heart rate reduces symptoms and improves clinical&#xD;
      outcomes in patients with heart failure. The effect of ivabradine and digoxin in heart&#xD;
      failure was compared.&#xD;
&#xD;
      Patients 22 patients with ischemic heart failure, AF, and diastolic dysfunction with&#xD;
      preserved left ventricular systolic function were treated with digoxin and ivabradine for 3&#xD;
      months, according to a randomization cross-over design.&#xD;
&#xD;
      Collected data Medical history, physical examination, laboratory (including proBNP and serum&#xD;
      digoxin concentrations), ECG, 6-minute walk test, and echocardiographic data (LVEF, LAVi,&#xD;
      e/e1 ratio).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Protocol This is an investigator-started study, coded GC&amp;PJ-dig-Iva 2009-2012. The study was&#xD;
      planned according to the Good Clinical Quality standards and the analysis was performed using&#xD;
      an intention-to-treat method. The protocol was approved from an Ethics Committee. Selected&#xD;
      patients gave their written informed consent. The family practitioners agreed and obtained&#xD;
      the data and analysis. Collected data were analyzed from single-blinded investigators&#xD;
      (without knowledge of the used test drug and time of collection).&#xD;
&#xD;
      Patients Study design: same patients were assigned to DIG or IVA for 3 months, according to a&#xD;
      randomization cross-over design.&#xD;
&#xD;
      Tested drugs Commercial brands of digoxin and ivabradine were used. Digoxin was given by&#xD;
      mouth at a dose of 0.125 mg/day, 5 times per week, for 3 months.&#xD;
&#xD;
      Ivabradine was given by mouth at a dose of 7.5 mg bid for 3 months.&#xD;
&#xD;
      Inclusion criteria Chronic and stable coronary artery disease Permanent atrial fibrillation.&#xD;
      Diastolic dysfunction with maintained systolic function.&#xD;
&#xD;
      Exclusion criteria Unstable angina pectoris. Reduced systolic cardiac function (LVEF&lt;52%).&#xD;
      Normal diastolic function. Diabetes requiring insulin. Moderate or severe renal or hepatic&#xD;
      dysfunction. Technically insufficient echocardiographic quality.&#xD;
&#xD;
      Collected data Medical history and concomitant medications. Physical examination was&#xD;
      performed. Laboratory values (including proBNP and serum digoxin concentration). ECG.&#xD;
      Echocardiography. 6-minute walk test.&#xD;
&#xD;
      Statistical Analyses Data are expressed as mean ± 1 SD. Absolute values and percent changes&#xD;
      in relation to baseline measurements were analyzed. The 2 hypotheses tested were: null&#xD;
      hypothesis: mu1-mu2=0.0, and alternative hypothesis: mu1-mu2&gt;&gt;0.0. Comparisons within groups&#xD;
      were made using paired t tests or the non-parametric Wilcoxon signed-rank test, where&#xD;
      appropriate. Between-group comparisons were performed by unpaired t tests or the&#xD;
      non-parametric Mann-Whitney U test, respectively. Chi-square test or Kruskal-Wallis test were&#xD;
      used to compare continuous normally or not normally distributed and qualitative variables,&#xD;
      where appropriate. Multivariate analysis of variance was performed. A p value of &lt; 0.05 was&#xD;
      considered statistically significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2008</start_date>
  <completion_date type="Actual">February 2012</completion_date>
  <primary_completion_date type="Actual">February 2012</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Comparative therapeutic effect.</measure>
    <time_frame>6 months</time_frame>
    <description>Effects on symptoms and signs of cardiac failure.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Cardiac Failure</condition>
  <arm_group>
    <arm_group_label>Ivabradine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ivabradine, 7,5 mg b.id. by mouth for 14-16 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Digoxin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Digoxin 0.125 mg once a day, 5 times per week, for 12-14 weeks by mouth.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivabradine</intervention_name>
    <description>7.5 my b.id. by mouth for 12-14 weeks</description>
    <arm_group_label>Ivabradine</arm_group_label>
    <other_name>Procoralan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Digoxin</intervention_name>
    <description>1.25 mg once a day by mouth, for 12-14 weeks.</description>
    <arm_group_label>Digoxin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All patients had heart failure NYHA (New York Heart Association) class III. All had chronic&#xD;
        and stable coronary artery disease which had been treated with percutaneous dilatation and&#xD;
        stenting, and/or aortocoronary bypass. The pathology had induced a permanent AF and heart&#xD;
        failure with left ventricular diastolic dysfunction and preserved systolic function.&#xD;
        Preserved systolic function was defined by a LVEF (left ventricular ejection fraction)&#xD;
        ≥52%. Left ventricular diastolic dysfunction was defined by a e/e1 ratio &gt; 15 (septal&#xD;
        spectral tissue-Doppler).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Unstable myocardial ischemia, reduced systolic cardiac function (LVEF&lt;52%), diabetes&#xD;
        mellitus requiring insulin, moderate or severe renal or hepatic dysfunction, or technically&#xD;
        insufficient echocardiography.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>78 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Giuseppe Cocco, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cardiologist, senior lecturer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cardiology office</name>
      <address>
        <city>Rheinfelden</city>
        <state>Argovia</state>
        <zip>CH-4310</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <results_reference>
    <citation>Cocco G, Jerie P. Comparison between ivabradine and low-dose digoxin in the therapy of diastolic heart failure with preserved left ventricular systolic function. Clin Pract. 2013 Nov 4;3(2):e29. doi: 10.4081/cp.2013.e29. eCollection 2013 Aug 2.</citation>
    <PMID>24765517</PMID>
  </results_reference>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>September 12, 2012</study_first_submitted>
  <study_first_submitted_qc>October 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <last_update_submitted>November 8, 2013</last_update_submitted>
  <last_update_submitted_qc>November 8, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 11, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cocco, Giuseppe, M.D.</investigator_affiliation>
    <investigator_full_name>Cocco G., M.D.</investigator_full_name>
    <investigator_title>M.D., FESC</investigator_title>
  </responsible_party>
  <keyword>Digoxin</keyword>
  <keyword>Ivabradine</keyword>
  <keyword>with atrial fibrillation.</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>Digoxin</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/NCT01699776
org study id: CG&PJ-Dig-Iva 2009-2012
nct id: NCT01699776
lead sponsor: 
collaborator: 
has dmc: Yes
It is established that at a serum concentration 0.5-0.9 ng/ml digoxin is effective in
      patients with heart failure, especially in the presence of atrial fibrillation (AF). It is
      the claimed that ivabradine by lowering heart rate reduces symptoms and improves clinical
      outcomes in patients with heart failure. The effect of ivabradine and digoxin in heart
      failure was compared.

      Patients 22 patients with ischemic heart failure, AF, and diastolic dysfunction with
      preserved left ventricular systolic function were treated with digoxin and ivabradine for 3
      months, according to a randomization cross-over design.

      Collected data Medical history, physical examination, laboratory (including proBNP and serum
      digoxin concentrations), ECG, 6-minute walk test, and echocardiographic data (LVEF, LAVi,
      e/e1 ratio).
Protocol This is an investigator-started study, coded GC&PJ-dig-Iva 2009-2012. The study was
      planned according to the Good Clinical Quality standards and the analysis was performed using
      an intention-to-treat method. The protocol was approved from an Ethics Committee. Selected
      patients gave their written informed consent. The family practitioners agreed and obtained
      the data and analysis. Collected data were analyzed from single-blinded investigators
      (without knowledge of the used test drug and time of collection).

      Patients Study design: same patients were assigned to DIG or IVA for 3 months, according to a
      randomization cross-over design.

      Tested drugs Commercial brands of digoxin and ivabradine were used. Digoxin was given by
      mouth at a dose of 0.125 mg/day, 5 times per week, for 3 months.

      Ivabradine was given by mouth at a dose of 7.5 mg bid for 3 months.

      Inclusion criteria Chronic and stable coronary artery disease Permanent atrial fibrillation.
      Diastolic dysfunction with maintained systolic function.

      Exclusion criteria Unstable angina pectoris. Reduced systolic cardiac function (LVEF<52%).
      Normal diastolic function. Diabetes requiring insulin. Moderate or severe renal or hepatic
      dysfunction. Technically insufficient echocardiographic quality.

      Collected data Medical history and concomitant medications. Physical examination was
      performed. Laboratory values (including proBNP and serum digoxin concentration). ECG.
      Echocardiography. 6-minute walk test.

      Statistical Analyses Data are expressed as mean ± 1 SD. Absolute values and percent changes
      in relation to baseline measurements were analyzed. The 2 hypotheses tested were: null
      hypothesis: mu1-mu2=0.0, and alternative hypothesis: mu1-mu2>>0.0. Comparisons within groups
      were made using paired t tests or the non-parametric Wilcoxon signed-rank test, where
      appropriate. Between-group comparisons were performed by unpaired t tests or the
      non-parametric Mann-Whitney U test, respectively. Chi-square test or Kruskal-Wallis test were
      used to compare continuous normally or not normally distributed and qualitative variables,
      where appropriate. Multivariate analysis of variance was performed. A p value of < 0.05 was
      considered statistically significant.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Comparative therapeutic effect.
time frame: 6 months
description: Effects on symptoms and signs of cardiac failure.
arm group label: Ivabradine
arm group type: Active Comparator
description: Ivabradine, 7,5 mg b.id. by mouth for 14-16 weeks.
arm group label: Digoxin
arm group type: Active Comparator
description: Digoxin 0.125 mg once a day, 5 times per week, for 12-14 weeks by mouth.
intervention type: Drug
intervention name: Ivabradine
description: 7.5 my b.id. by mouth for 12-14 weeks
arm group label: Ivabradine
other name: Procoralan
intervention type: Drug
intervention name: Digoxin
description: 1.25 mg once a day by mouth, for 12-14 weeks.
arm group label: Digoxin
criteria: 
gender: All
minimum age: 60 Years
maximum age: 78 Years
healthy volunteers: No
last name: Giuseppe Cocco, MD
role: Principal Investigator
affiliation: Cardiologist, senior lecturer
facility: 
country: Switzerland
citation: Cocco G, Jerie P. Comparison between ivabradine and low-dose digoxin in the therapy of diastolic heart failure with preserved left ventricular systolic function. Clin Pract. 2013 Nov 4;3(2):e29. doi: 10.4081/cp.2013.e29. eCollection 2013 Aug 2.
PMID: 24765517
responsible party type: Principal Investigator
investigator affiliation: Cocco, Giuseppe, M.D.
investigator full name: Cocco G., M.D.
investigator title: M.D., FESC
mesh term: Heart Failure
mesh term: Digoxin