<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/NCT03807037</url>
  </required_header>
  <id_info>
    <org_study_id>T3-AF 34963</org_study_id>
    <nct_id>NCT03807037</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Tocotrienols in Post-CABG Atrial Fibrillation</brief_title>
  <official_title>Safety of Tocotrienols in Atrial Fibrillation After Coronary Artery Bypass Grafting Surgery: A Randomized Controlled Exploratory Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Monash University Malaysia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut Jantung Negara</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Monash University Malaysia</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>
      This study is a prospective, randomized, controlled trial with parallel groups to assess the&#xD;
      effects of tocotrienol in the occurrence of atrial fibrillation (AF) post-CABG.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      At present, guidelines exist in Europe and the USA on the pharmacological prophylaxis and&#xD;
      management of postoperative AF. However, these are subject to a number of limitations&#xD;
      including treatment failure, toxicity and pro-arrhythmogenicity. Hence, efforts have been&#xD;
      made to develop alternative preventive strategies. The understanding of the role of oxidative&#xD;
      stress as a mechanism for AF development has made way for antioxidant vitamins as novel&#xD;
      therapeutic and preventive agents.&#xD;
&#xD;
      In view of emerging evidence on the HMG-CoA reductase inhibitory role in the incidence of AF&#xD;
      and established inhibitory properties of tocotrienols, we postulate that supplementation with&#xD;
      tocotrienols may exert therapeutic advantage in the safety endpoints of post-CABG. The&#xD;
      modulation of oxidative stress status and anti-inflammatory via HMG-CoA reductase inhibition&#xD;
      may work synergistically in affecting the incidence of AF post-CABG.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 17, 2018</start_date>
  <completion_date type="Actual">December 30, 2021</completion_date>
  <primary_completion_date type="Actual">December 30, 2021</primary_completion_date>
  <phase>Phase 2/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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of AF</measure>
    <time_frame>24-48 hours post-operation, up to 6-weeks after discharge</time_frame>
    <description>Between group incidence of post-operative AF</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay (LoHS) after surgery</measure>
    <time_frame>Up to 2 months post-operation</time_frame>
    <description>Total Intensive/coronary care unit length of stay,&#xD;
Total days of High Dependency Unit stay;&#xD;
Total hospital length of stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life (HRQoL)</measure>
    <time_frame>6-weeks after discharge</time_frame>
    <description>Short-Form 36 Questionnaires (SF-36)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">250</enrollment>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mixed tocotrienols 200mg, twice daily (400mg/day)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching Placebo (Placebo oral capsule)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Tocotrienols</intervention_name>
    <description>Mixed tocotrienols (derived from palm oil) to be orally administered at 200mg (1 capsule) twice daily, to achieve dosage of 400mg/day</description>
    <arm_group_label>Treatment</arm_group_label>
    <other_name>Tocovid Suprabio</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>Matching placebo to be administered orally at 1 capsule, twice daily</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females&#xD;
&#xD;
          2. More than 18 years of age&#xD;
&#xD;
          3. Elective, on-pump surgery of coronary artery revascularization, isolated or combined&#xD;
             valve surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Less than 18 years of age&#xD;
&#xD;
          2. Refusal to have surgery&#xD;
&#xD;
          3. Urgent or emergency surgery&#xD;
&#xD;
          4. Off-pump surgery&#xD;
&#xD;
          5. Poor LV (EF &lt; 30%)&#xD;
&#xD;
          6. Inability to give informed consent&#xD;
&#xD;
          7. Documented allergy to palm oil or Vitamin E&#xD;
&#xD;
          8. Documented AF or any form of arrhythmia pre-operatively&#xD;
&#xD;
          9. Currently on or indicated for long-term corticosteroid treatment&#xD;
&#xD;
         10. Patients who have been included in any other clinical trial within the previous three&#xD;
             months&#xD;
&#xD;
         11. Patients who are on supplementation of Vitamin E or other potent anti-oxidants up to 1&#xD;
             month before randomisation&#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_official>
    <last_name>Ahmad Farouk Musa, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Monash University Malaysia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut Jantung Negara</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>50400</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Malaysia</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>August 23, 2022</last_update_submitted>
  <last_update_submitted_qc>August 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>atrial fibrillation,tocotrienol,coronary artery bypass grafting</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tocotrienols</mesh_term>
    <mesh_term>Vitamin E</mesh_term>
    <mesh_term>Tocopherols</mesh_term>
    <mesh_term>Tocovid</mesh_term>
  </intervention_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/NCT03807037
org study id: T3-AF 34963
nct id: NCT03807037
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is a prospective, randomized, controlled trial with parallel groups to assess the
      effects of tocotrienol in the occurrence of atrial fibrillation (AF) post-CABG.
At present, guidelines exist in Europe and the USA on the pharmacological prophylaxis and
      management of postoperative AF. However, these are subject to a number of limitations
      including treatment failure, toxicity and pro-arrhythmogenicity. Hence, efforts have been
      made to develop alternative preventive strategies. The understanding of the role of oxidative
      stress as a mechanism for AF development has made way for antioxidant vitamins as novel
      therapeutic and preventive agents.

      In view of emerging evidence on the HMG-CoA reductase inhibitory role in the incidence of AF
      and established inhibitory properties of tocotrienols, we postulate that supplementation with
      tocotrienols may exert therapeutic advantage in the safety endpoints of post-CABG. The
      modulation of oxidative stress status and anti-inflammatory via HMG-CoA reductase inhibition
      may work synergistically in affecting the incidence of AF post-CABG.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Incidence of AF
time frame: 24-48 hours post-operation, up to 6-weeks after discharge
description: Between group incidence of post-operative AF
measure: Length of hospital stay (LoHS) after surgery
time frame: Up to 2 months post-operation
description: Total Intensive/coronary care unit length of stay,
Total days of High Dependency Unit stay;
Total hospital length of stay
measure: Health-related quality of life (HRQoL)
time frame: 6-weeks after discharge
description: Short-Form 36 Questionnaires (SF-36)
arm group label: Treatment
arm group type: Experimental
description: Mixed tocotrienols 200mg, twice daily (400mg/day)
arm group label: Control
arm group type: Placebo Comparator
description: Matching Placebo (Placebo oral capsule)
intervention type: Dietary Supplement
intervention name: Tocotrienols
description: Mixed tocotrienols (derived from palm oil) to be orally administered at 200mg (1 capsule) twice daily, to achieve dosage of 400mg/day
arm group label: Treatment
other name: Tocovid Suprabio
intervention type: Drug
intervention name: Placebo oral capsule
description: Matching placebo to be administered orally at 1 capsule, twice daily
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ahmad Farouk Musa, MD
role: Principal Investigator
affiliation: Monash University Malaysia
facility: 
country: Malaysia
responsible party type: Sponsor
mesh term: Atrial Fibrillation
mesh term: Tocotrienols
mesh term: Vitamin E
mesh term: Tocopherols
mesh term: Tocovid
sharing ipd: No