Safety and Efficacy of Tocotrienols in Post-CABG Atrial Fibrillation

Safety of Tocotrienols in Atrial Fibrillation After Coronary Artery Bypass Grafting Surgery: A Randomized Controlled Exploratory Trial

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Dietary supplement: Tocotrienols; Drug: Placebo oral capsule

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia, 50400
    • Institut Jantung Negara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females
2. More than 18 years of age
3. Elective, on-pump surgery of coronary artery revascularization, isolated or combined valve surgery

Exclusion Criteria:

1. Less than 18 years of age
2. Refusal to have surgery
3. Urgent or emergency surgery
4. Off-pump surgery
5. Poor LV (EF < 30%)
6. Inability to give informed consent
7. Documented allergy to palm oil or Vitamin E
8. Documented AF or any form of arrhythmia pre-operatively
9. Currently on or indicated for long-term corticosteroid treatment
10. Patients who have been included in any other clinical trial within the previous three months
11. Patients who are on supplementation of Vitamin E or other potent anti-oxidants up to 1 month before randomisation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Mixed tocotrienols 200mg, twice daily (400mg/day)	Dietary supplement: Tocotrienols; Mixed tocotrienols (derived from palm oil) to be orally administered at 200mg (1 capsule) twice daily, to achieve dosage of 400mg/day; Other Names: Tocovid Suprabio
Placebo Comparator: Control; Matching Placebo (Placebo oral capsule)	Drug: Placebo oral capsule; Matching placebo to be administered orally at 1 capsule, twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of AF	Between group incidence of post-operative AF	24-48 hours post-operation, up to 6-weeks after discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay (LoHS) after surgery	Total Intensive/coronary care unit length of stay,; Total days of High Dependency Unit stay;; Total hospital length of stay	Up to 2 months post-operation
Health-related quality of life (HRQoL)	Short-Form 36 Questionnaires (SF-36)	6-weeks after discharge

Collaborators and Investigators

• Sponsor: Monash University Malaysia
• Collaborators: Institut Jantung Negara
• Investigators: Principal Investigator: Ahmad Farouk Musa, MD, Monash University Malaysia

Publications and helpful links

General Publications

• Musa AF, Dillon J, Md Taib ME, Yunus AM, Sanusi AR, Nordin MN, Smith JA. A double-blind randomised controlled trial on the effect of Tocovid, a tocotrienol-rich capsule on postoperative atrial fibrillation at the National Heart Institute, Kuala Lumpur: an interim blinded analysis. J Cardiothorac Surg. 2021 Nov 24;16(1):340. doi: 10.1186/s13019-021-01721-6.

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2018
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): December 30, 2021

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: January 14, 2019
• First Posted (Actual): January 16, 2019

Study Record Updates

• Last Update Posted (Actual): August 25, 2022
• Last Update Submitted That Met QC Criteria: August 23, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: atrial fibrillation,tocotrienol,coronary artery bypass grafting
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E; Tocopherols; Tocotrienols; Tocovid
• Other Study ID Numbers: T3-AF 34963

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No