Effect of Parenteral Alpha-Tocopherol in the Definitive Surgery of Tetralogy of Fallot

Not Applicable

Completed

• Conditions: Tetralogy of Fallot (TOF); Alpha-tocopherol; Cardiac Surgery
• Interventions: Drug: alpha-Tocopherol; Drug: Sterile Water for Injection

• Registration Number: NCT07194304
• Lead Sponsor: Dr Cipto Mangunkusumo General Hospital

Brief Summary

Introduction:

Tetralogy of Fallot (ToF) correction with cardiopulmonary bypass (CPB) poses a risk of ischemia-reperfusion injury, especially in cyanotic myocardium. Alpha-tocopherol, a potent antioxidant, may reduce myocardial damage during surgery.

Methods:

This randomized controlled trial included 58 ToF patients aged 1-10 years undergoing definitive surgery with CPB at Integrated Heart Center, Cipto Mangunkusumo Hospital. Patients were randomly assigned to receive either parenteral alpha-tocopherol (4 mg/kg) or placebo at the initiation of CPB. The primary outcome was postoperative troponin I level.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-05-01
• Primary Completion: 2024-01-01
• Study Completion: 2025-06-01
• Study First Submitted: 2025-07-04
• Status Verified: 2025-09
• Study First Submitted QC: 2025-09-18
• Last Update Submitted: 2025-09-18
• Study First Posted: 2025-09-26
• Last Update Posted: 2025-09-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Diagnosis of congenital heart disease Tetralogy of Fallot (ToF)
• Age between 1 and 10 years
• Scheduled for definitive repair of ToF using cardiopulmonary bypass (CPB) at PJT-RSCM

Exclusion Criteria

• History of prior palliative surgery (e.g., Blalock-Taussig shunt)
• Presence of additional congenital heart disease requiring major modification or addition of surgical procedures
• History of central nervous system disorder or stroke
• History of cardiopulmonary resuscitation (CPR)
• Undergoing redo surgery (e.g., residual stenosis, bleeding)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
alpha-tocopherol	alpha-Tocopherol	assigned to receive either parenteral alpha-tocopherol (4 mg/kg)
sterile water for injection	Sterile Water for Injection	the control group received a placebo (sterile water for injection/aquabidest)

Primary Outcome Measures

Name	Time	Method
Change in Serum Troponin I Concentration (ng/L)	Before surgery, 1 hour after surgery, and 8 hours after surgery	Serum Troponin I concentration will be measured at baseline (before surgery), 1 hour after surgery, and 8 hours after surgery to assess the extent of myocardial injury associated with cardiopulmonary bypass during Tetralogy of Fallot repair.

Secondary Outcome Measures

Name	Time	Method
Change in Serum Malondialdehyde (MDA) Concentration (ng/mL)	Before surgery, 1 hour after surgery, and 8 hours after surgery	Serum malondialdehyde (MDA), a biomarker of oxidative stress, will be measured at baseline (before surgery), 1 hour after surgery, and 8 hours after surgery to evaluate oxidative injury associated with cardiopulmonary bypass during Tetralogy of Fallot repair.
Change in Serum Lactate Concentration (mmol/L)	Before surgery, 1 hour, 6 hours, 12 hours, and 24 hours after surgery	Serum lactate levels will be measured at baseline (before surgery), and at 1 hour, 6 hours, 12 hours, and 24 hours after surgery to evaluate tissue perfusion and metabolic response associated with cardiopulmonary bypass during Tetralogy of Fallot repair.
Myocardial Injury Score (Histopathology, Scale 0-3)	15 minutes after release of the aortic cross-clamp	Myocardial tissue injury will be assessed from biopsy samples collected 15 minutes after release of the aortic cross-clamp. Injury will be graded on a histopathological scale ranging from 0 to 3, where 0 = no injury and 3 = severe injury. Higher scores indicate worse myocardial damage.
Apoptotic Index (% of Apoptotic Cardiomyocytes)	tissue sample is collected 15 minutes after releasing the aortic cross clamp	The apoptotic index will be calculated from myocardial tissue samples collected 15 minutes after release of the aortic cross-clamp. Sections are stained with TUNEL and examined at 40× magnification across 6 hotspot areas. The index is expressed as the percentage of TUNEL-positive cardiomyocytes per 100 cardiomyocytes. The scale ranges from 0% (no apoptosis) to 100% (all cells apoptotic). Higher values indicate greater myocardial apoptosis.
Duration of Mechanical Ventilation (hours)	From end of surgery until extubation	Duration of postoperative mechanical ventilation will be recorded in hours.
anti-cTnI	tissue sample is collected 15 minutes after releasing the aortic cross clamp
GPx expression	tissue sample is collected 15 minutes after releasing the aortic cross clamp
Intensive Care Unit Length of Stay (days)	From ICU admission until ICU discharge, assessed up to 14 days	ICU length of stay will be recorded in days from ICU admission until ICU discharge.
Hospital Length of Stay (days)	From hospital admission until hospital discharge, assessed up to 30 days	Hospital length of stay will be recorded in days from hospital admission until discharge.
Vasoactive-Inotropic Score (VIS, Scale 0-X)	First 24 hours after surgery	Vasoactive-Inotropic Score (VIS) will be calculated to quantify the amount of vasoactive support required after surgery. The VIS scale ranges from 0 to an open-ended maximum value; higher scores indicate greater need for vasoactive support and worse hemodynamic status.

Trial Locations

Locations (1)

Cipto Mangunkusumo Hospital; 🇮🇩 Jakarta, Indonesia