<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/NCT04448899</url>
  </required_header>
  <id_info>
    <org_study_id>Ivabradine in CHF</org_study_id>
    <nct_id>NCT04448899</nct_id>
  </id_info>
  <brief_title>Ivabradine in Patients With Congestive Heart Failure</brief_title>
  <official_title>Effects of Ivabradine on Neopterin and NT-Pro BNP in Patients With Congestive Heart Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Damanhour University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Damanhour 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>
      The aim of this study is to assess the efficacy of Ivabradine therapy in patients with&#xD;
      congestive heart failure using the cardiac biomarkers NT-Pro BNP and Neopterin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  Approval will be obtained from Research Ethics Committee of Faculty of Pharmacy,&#xD;
           Damanhour University&#xD;
&#xD;
        -  All participants have agreed to take part in this clinical study and provide informed&#xD;
           consent&#xD;
&#xD;
        -  A 3 months, prospective interventional study.&#xD;
&#xD;
        -  Sixty ambulatory, clinically stable symptomatic patients with systolic chronic HF (≥ 4&#xD;
           weeks), on optimized standard medical therapy were consecutively included and randomly&#xD;
           allocated to the ivabradine group (n=30) and non-ivabradine group (n=30).&#xD;
&#xD;
        -  The baseline evaluation comprised physical examination, NYHA class, 12-lead&#xD;
           electrocardi¬ography (ECG), Echocardiography, blood sampling for laboratory&#xD;
           measurements, including NT-Pro BNP and Neopterin.&#xD;
&#xD;
        -  Patients in the Ivabradine group were administered Ivabradine 5 mg twice daily and doses&#xD;
           (2.5, 5, 7.5 mg) were to be adjusted upwards or downwards at every visit according to HR&#xD;
           at rest and tolerability.&#xD;
&#xD;
        -  Patients were followed up after 1 week of initiation of ivabradine therapy then monthly&#xD;
           till the end of the study.&#xD;
&#xD;
        -  Peripheral venous blood samples were drawn between 8 and 9 am after a 30-min rest in the&#xD;
           supine position. Serum samples were frozen at -80°C until assay.&#xD;
&#xD;
        -  Levels of NT-Pro BNP and Neopterin were detected using ELISA kits as prescribed by&#xD;
           manufacturer.&#xD;
&#xD;
        -  Statistical tests appropriate to the study will be conducted to evaluate significance of&#xD;
           results&#xD;
&#xD;
        -  Results, conclusion, discussion and recommendations will be given&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Actual">February 5, 2021</completion_date>
  <primary_completion_date type="Actual">February 1, 2021</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>Double (Participant, Investigator)</masking>
    <masking_description>double-blind study</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>NT-Pro BNP</measure>
    <time_frame>three months</time_frame>
    <description>Serum BNP (pg/ml)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neopterin</measure>
    <time_frame>three months</time_frame>
    <description>Serum Neopterin (nmol/L)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Heart Rate</measure>
    <time_frame>Three Months</time_frame>
    <description>Heart Rate (Beat/Minute)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Congestive Heart Failure</condition>
  <arm_group>
    <arm_group_label>Ivabradine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients administered Ivabradine 5 mg twice daily and doses (2.5, 5, 7.5 mg) were to be adjusted upwards or downwards at every visit according to HR at rest and tolerability.&#xD;
Patients were followed up after 1 week of initiation of ivabradine therapy then monthly till the end of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients administered a placebo twice daily. Patients were followed up after 1 week of initiation of the study then monthly till the end of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivabradine Oral Tablet</intervention_name>
    <description>Ivabradine 5 mg twice daily and doses (2.5, 5, 7.5 mg) were to be adjusted upwards or downwards at every visit according to HR at rest and tolerability plus their standard treatment.</description>
    <arm_group_label>Ivabradine</arm_group_label>
    <other_name>Procoralan 5 mg film-coated tablets</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Blacebo plus standard treatment</intervention_name>
    <description>Blacebo plus standard treatment</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with chronic HF, on optimized medical therapy according to European Society&#xD;
             of Cardiol¬ogy guidelines, with LV ejection fraction (LVEF) &lt; 35% according to the&#xD;
             Simpson method, New York Heart Association (NYHA) class II-III, and sinus rhythm and&#xD;
             resting HR &gt; 70/min were eligible for inclusion in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  acute decompen¬sation (acute coronary syndromes and acute HF);&#xD;
&#xD;
          -  hemodynamically significant valve disease;&#xD;
&#xD;
          -  cer¬ebrovascular events during the previous 6 months;&#xD;
&#xD;
          -  dysfunctional prosthetic heart valve;&#xD;
&#xD;
          -  obstructive or non-obstructive cardiomyopathy; uncorrected congenital heart disease;&#xD;
             active myocarditis;&#xD;
&#xD;
          -  a his¬tory of resuscitation from sudden death; an absence of stable sinus rhythm,&#xD;
             severe arrhythmias; HR &lt; 60 bpm; sick sinus syndrome; second-degree and third-degree&#xD;
             atrioventricular block;&#xD;
&#xD;
          -  severe obesity (body mass index &gt; 36 kg/m²);&#xD;
&#xD;
          -  established or sus¬pected pulmonary diseases (vital capacity &lt; 80% or forced&#xD;
             expiratory volume in 1 s &lt; 80% of age spe¬cific and sex-specific reference values);&#xD;
&#xD;
          -  hemoglobin ≤ 11 g/dL;&#xD;
&#xD;
          -  treatment with non-dihydropyridine calcium-channel blockers, class I antiarrhythmic&#xD;
             agents, strong inhibitors of cytochrome P450-3A4, or QT interval-prolonging&#xD;
             medications;&#xD;
&#xD;
          -  acute and chronic kidney failure;&#xD;
&#xD;
          -  pregnancy; hypo- and hy¬perthyroidism or acute infections.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rehab Werida, Lecturer</last_name>
    <role>Study Director</role>
    <affiliation>Damanhour University, Faculty of Pharmacy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jayda M Dogheim, B. Pharm</last_name>
    <role>Principal Investigator</role>
    <affiliation>Alexandria University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tanta University Hospital</name>
      <address>
        <city>Tanta</city>
        <state>El-Gharbia</state>
        <zip>31527</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <results_reference>
    <citation>Komajda M, Tavazzi L, Francq BG, Bohm M, Borer JS, Ford I, Swedberg K; SHIFT Investigators. Efficacy and safety of ivabradine in patients with chronic systolic heart failure and diabetes: an analysis from the SHIFT trial. Eur J Heart Fail. 2015 Dec;17(12):1294-301. doi: 10.1002/ejhf.347. Epub 2015 Sep 16.</citation>
    <PMID>26377342</PMID>
  </results_reference>
  <results_reference>
    <citation>Tavazzi L, Swedberg K, Komajda M, Bohm M, Borer JS, Lainscak M, Ford I; SHIFT Investigators. Efficacy and safety of ivabradine in chronic heart failure across the age spectrum: insights from the SHIFT study. Eur J Heart Fail. 2013 Nov;15(11):1296-303. doi: 10.1093/eurjhf/hft102. Epub 2013 Jun 26.</citation>
    <PMID>23803951</PMID>
  </results_reference>
  <results_reference>
    <citation>Sasaki T, Takeishi Y, Suzuki S, Niizeki T, Kitahara T, Katoh S, Ishino M, Shishido T, Watanabe T, Kubota I. High serum level of neopterin is a risk factor of patients with heart failure. Int J Cardiol. 2010 Nov 19;145(2):318. doi: 10.1016/j.ijcard.2009.11.042. Epub 2010 Jan 6.</citation>
    <PMID>20051294</PMID>
  </results_reference>
  <results_reference>
    <citation>Richards M, Troughton RW. NT-proBNP in heart failure: therapy decisions and monitoring. Eur J Heart Fail. 2004 Mar 15;6(3):351-4. doi: 10.1016/j.ejheart.2004.01.003.</citation>
    <PMID>14987587</PMID>
  </results_reference>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 26, 2020</study_first_posted>
  <last_update_submitted>August 3, 2021</last_update_submitted>
  <last_update_submitted_qc>August 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Damanhour University</investigator_affiliation>
    <investigator_full_name>Rehab Werida</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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04448899
org study id: Ivabradine in CHF
nct id: NCT04448899
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to assess the efficacy of Ivabradine therapy in patients with
      congestive heart failure using the cardiac biomarkers NT-Pro BNP and Neopterin.
-  Approval will be obtained from Research Ethics Committee of Faculty of Pharmacy,
           Damanhour University

        -  All participants have agreed to take part in this clinical study and provide informed
           consent

        -  A 3 months, prospective interventional study.

        -  Sixty ambulatory, clinically stable symptomatic patients with systolic chronic HF (≥ 4
           weeks), on optimized standard medical therapy were consecutively included and randomly
           allocated to the ivabradine group (n=30) and non-ivabradine group (n=30).

        -  The baseline evaluation comprised physical examination, NYHA class, 12-lead
           electrocardi¬ography (ECG), Echocardiography, blood sampling for laboratory
           measurements, including NT-Pro BNP and Neopterin.

        -  Patients in the Ivabradine group were administered Ivabradine 5 mg twice daily and doses
           (2.5, 5, 7.5 mg) were to be adjusted upwards or downwards at every visit according to HR
           at rest and tolerability.

        -  Patients were followed up after 1 week of initiation of ivabradine therapy then monthly
           till the end of the study.

        -  Peripheral venous blood samples were drawn between 8 and 9 am after a 30-min rest in the
           supine position. Serum samples were frozen at -80°C until assay.

        -  Levels of NT-Pro BNP and Neopterin were detected using ELISA kits as prescribed by
           manufacturer.

        -  Statistical tests appropriate to the study will be conducted to evaluate significance of
           results

        -  Results, conclusion, discussion and recommendations will be given
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: double-blind study
measure: NT-Pro BNP
time frame: three months
description: Serum BNP (pg/ml)
measure: Neopterin
time frame: three months
description: Serum Neopterin (nmol/L)
measure: Heart Rate
time frame: Three Months
description: Heart Rate (Beat/Minute)
arm group label: Ivabradine
arm group type: Active Comparator
description: Patients administered Ivabradine 5 mg twice daily and doses (2.5, 5, 7.5 mg) were to be adjusted upwards or downwards at every visit according to HR at rest and tolerability.
Patients were followed up after 1 week of initiation of ivabradine therapy then monthly till the end of the study.
arm group label: Control
arm group type: Placebo Comparator
description: Patients administered a placebo twice daily. Patients were followed up after 1 week of initiation of the study then monthly till the end of the study.
intervention type: Drug
intervention name: Ivabradine Oral Tablet
description: Ivabradine 5 mg twice daily and doses (2.5, 5, 7.5 mg) were to be adjusted upwards or downwards at every visit according to HR at rest and tolerability plus their standard treatment.
arm group label: Ivabradine
other name: Procoralan 5 mg film-coated tablets
intervention type: Drug
intervention name: Blacebo plus standard treatment
description: Blacebo plus standard treatment
arm group label: Control
criteria: 
gender: All
minimum age: 30 Years
maximum age: 70 Years
healthy volunteers: No
last name: Rehab Werida, Lecturer
role: Study Director
affiliation: Damanhour University, Faculty of Pharmacy
last name: Jayda M Dogheim, B. Pharm
role: Principal Investigator
affiliation: Alexandria University
facility: 
country: Egypt
citation: Komajda M, Tavazzi L, Francq BG, Bohm M, Borer JS, Ford I, Swedberg K; SHIFT Investigators. Efficacy and safety of ivabradine in patients with chronic systolic heart failure and diabetes: an analysis from the SHIFT trial. Eur J Heart Fail. 2015 Dec;17(12):1294-301. doi: 10.1002/ejhf.347. Epub 2015 Sep 16.
PMID: 26377342
citation: Tavazzi L, Swedberg K, Komajda M, Bohm M, Borer JS, Lainscak M, Ford I; SHIFT Investigators. Efficacy and safety of ivabradine in chronic heart failure across the age spectrum: insights from the SHIFT study. Eur J Heart Fail. 2013 Nov;15(11):1296-303. doi: 10.1093/eurjhf/hft102. Epub 2013 Jun 26.
PMID: 23803951
citation: Sasaki T, Takeishi Y, Suzuki S, Niizeki T, Kitahara T, Katoh S, Ishino M, Shishido T, Watanabe T, Kubota I. High serum level of neopterin is a risk factor of patients with heart failure. Int J Cardiol. 2010 Nov 19;145(2):318. doi: 10.1016/j.ijcard.2009.11.042. Epub 2010 Jan 6.
PMID: 20051294
citation: Richards M, Troughton RW. NT-proBNP in heart failure: therapy decisions and monitoring. Eur J Heart Fail. 2004 Mar 15;6(3):351-4. doi: 10.1016/j.ejheart.2004.01.003.
PMID: 14987587
responsible party type: Principal Investigator
investigator affiliation: Damanhour University
investigator full name: Rehab Werida
investigator title: Principal Investigator
mesh term: Heart Failure
sharing ipd: No