Thyroid Hormone Replacement After Coronary Artery Bypass Grafting for Patients With Subclinical Hypothyroidism (RepleniSH)

The goal of this clinical trial is to find out whether levothyroxine reduces complications and improves the prognosis of patients with subclinical hypothyroidism (SCH) undergoing coronary artery bypass grafting (CABG).

The main questions this study aims to answer are:

• Does levothyroxine reduce major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and new arrhythmias, in SCH patients undergoing CABG? Researchers will compare patients who take levothyroxine with those who do not.

Participants will:

• Be randomly assigned to either receive levothyroxine or not
• Start the medication one day before surgery if assigned to the treatment group.
• Have regular follow-up visits to check thyroid function and cardiovascular events for up to five years after surgery.

Study Overview

• Status: Recruiting
• Conditions: Subclinical Hypothyroidism
• Intervention / Treatment: Drug: levothyroxine

• Study Type: Interventional
• Enrollment (Estimated): 338
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Min Joo Kim, Professor; Phone Number: +82-31-787-7855; Email: chorong24@gmail.com

Study Locations

• South Korea
  • Seongnam-si, South Korea, 13620
    • Recruiting
    • Department of Internal Medicine, Seoul National University Bundang Hospital
    • Contact: Kang; Phone Number: +82-787-7029; Email: hjk@snubh.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Eligibility Criteria

• Adults aged 19 to 90 years.
• Patients scheduled to undergo coronary artery bypass graft (CABG) surgery.
• Subclinical hypothyroidism (SCH), defined as a normal free thyroxine (free T4) level and a thyroid-stimulating hormone (TSH) level greater than 4 μIU/mL, based on testing performed within 31 days prior to surgery.

Exclusion Criteria:

• Patients who underwent repeat or emergency CABG surgery
• Use of LT4 within the previous 4 weeks
• Use of antithyroid drug use (propylthiouracil, methimazole, or carbimazole) within the previous 3 months
• Severe comorbid conditions with a life expectancy of less than 1 year (e.g. advanced malignancy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LT4 group; Participants in this group will receive levothyroxine	Drug: levothyroxine; Intervention description: Participants assigned to the LT4 group will begin receiving levothyroxine the day before CABG. The initial dose is 25 μg once daily, or 12.5 μg for participants weighing less than 60 kg. The dose will then be adjusted based on thyroid function test results to achieve target TSH levels of 0.4-2.0 μIU/mL.
No Intervention: Control group; Participants in this group will not receive levothyroxine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A composite of MACE within 4months after surgery	A composite of major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and the occurrence of new arrhythmias assessed within 4 months after CABG.	within 4months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who experience cardiovascular death within 4 months after surgery	Number of participants who experience cardiovascular death within 4 months after CABG	within 4months after surgery
Number of participants who experience nonfatal myocardial infarction within 4 months after surgery	Number of participants who experience nonfatal myocardial infarction within 4 months after CABG	within 4months after surgery
Number of participants who experience nonfatal stroke within 4 months after surgery	Number of participants who experience nonfatal stroke within 4 months after CABG	within 4months after surgery
Number of participants who experience new arrhythmia within 4 months after surgery	Number of participants who experience new arrhythmia within 4 months after CABG	within 4months after surgery
A composite of MACE within 1 year after surgery	A composite of major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and the occurrence of new arrhythmias assessed within 1year after CABG	within 1 year after surgery
A composite of MACE within 5 year after surgery	A composite of major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and the occurrence of new arrhythmias assessed within 5 years after CABG	within 5 years after surgery
All-cause mortality within 5 years after surgery	All-cause mortality within 5 years after surgery	within 5 years after surgery
Change in LVEF from baseline to 1 year after surgery	Left ventricular ejection fraction (LVEF) will be measured using transthoracic echocardiography at baseline (pre-operative) and at 1 year post-operatively. The outcome will be reported as the mean change in LVEF (%) from baseline to 1 year.	From baseline to 1 year after surgery
Change in LV EDD from baseline to 1 year after surgery	Left ventricular end-diastolic diameter (LVEDD) will be measured using transthoracic echocardiography at baseline (pre-operative) and at 1 year post-operatively. The outcome will be reported as the mean change in LVEDD (%) from baseline to 1 year.	From baseline to 1 year after surgery
Change in LV ESD from baseline to 1 year after surgery	Left ventricular end-systolic diameter (LV ESD) will be measured using transthoracic echocardiography at baseline (pre-operative) and at 1 year post-operatively. The outcome will be reported as the mean change in LV ESD (%) from baseline to 1 year.	From baseline to 1 year after surgery
Change in LVMI from baseline to 1 year after surgery	Left ventricular mass index (LVMI) will be measured using transthoracic echocardiography at baseline (pre-operative) and at 1 year post-operatively. The outcome will be reported as the mean change in LVMI (%) from baseline to 1 year.	From baseline to 1 year after surgery
Change in LAMI from baseline to 1 year after surgery	Left atrial volume index (LAMI) will be measured using transthoracic echocardiography at baseline (pre-operative) and at 1 year post-operatively. The outcome will be reported as the mean change in LAMI (%) from baseline to 1 year.	From baseline to 1 year after surgery

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2022
• Primary Completion (Estimated): February 26, 2032
• Study Completion (Estimated): February 26, 2037

Study Registration Dates

• First Submitted: January 15, 2026
• First Submitted That Met QC Criteria: January 24, 2026
• First Posted (Actual): February 2, 2026

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 24, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: coronary artery bypass grafting; thyroid hormones; levothyroxine; subclinical hypothyroidism
• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Peptides, and Proteins; Amino Acids; Amino Acids, Aromatic; Amino Acids, Cyclic; Thyroid Hormones; Thyroxine
• Other Study ID Numbers: IRB-B-2110-717-003

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