Thyroid Hormone Replacement for Subclinical Hypothyroidism and Dyslipidemia in ASCVD (ThyroHeart-Lipid Study)

Study Overview
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Brief Summary
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In ASCVD patients complicated with subclinical hypothyroidism, the percentage of those who did not reach the target of lipid-lowering therapy (LDL-C>1.8mmol/L) is usually higher than that in population with normal thyroid function. The present study aims to randomly compare two lipid-lowering therapeutic strategies (statins only vs. statins combined with thyroid hormone supplement).

Official Title
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Thyroid Hormone Replacement for Subclinical Hypothyroidism and Dyslipidemia in Patients With Atherosclerotic Cardiovascular Diseases (ThyroHeart-Lipid Study)

Conditions
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Dyslipidemia, Subclinical hypothyroïdism, Statin, ASCVD

Intervention / Treatment
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* Drug: Pitavastatin and placebo
* Drug: Pitavastatin and levothyroxine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant female; Stable or unstable angina with evidence of myocardial ischemia; coronary angiography reveals stenosis lesions; Subclinical hypothyroidism defined as mild TSH elevation within 5-10mIU/L and normal serum thyroid hormone levels within reference ranges; Level of LDL-C is more than 1.8mmol/L before randomization. Participate in the trial voluntarily and signs the written informed consent form. Exclusion Criteria: Those who have participated in other drug or therapy equipment clinical trials but did not reach the main study endpoint time limit; Symptoms of severe heart failure (NYHA Class III and above) or left ventricular ejection fraction < 40% (ultrasound or left ventricle ngiography); Pregnant or lactating women; Complicated with severe organ dysfunction: large number of pericardial effusion; acute myocardial infarction; acute myocarditis; acute left heart failure; cardiogenic shock; severe arrhythmia, such as ventricular tachycardia, ventricular fibrillation, frequent atrial / ventricular premature beat, poor control of fast ventricular fibrillation, and bradycardia requiring pacemaker therapy, etc. Patients who are unable to withstand lipid-lowering therapy or thyroid hormone replacement due to allergy to statins or levothyroxine; Serum AST/ALT is three times higher than the upper limits of normal. Patient's life expectancy is less than 12 months; Those waiting for heart transplantation; Patients who are deemed by the researchers to have low compliance and unable to abide by the requirements and complete the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Pivastatin and placebo<br>After randomization, patients in Pivastatin + placebo group will receive pitavastatin and placebo. | Drug: Pitavastatin and placebo<br>* The initial dosage of pitavastatin is 2mg, and it will be regulated according to the level of LDL-C and the upper limit is 4mg.Since the investigators are blind to the arms,the fake regulation of placebo dosage will be same as the Pitavastatin and levothyroxine group.<br>|
| Experimental: Pivastatin and LT-4<br>After randomization, patients in combination group will receive pitavastatin as the lipid-lowering therapy and take levothyroxine as the thyroid hormone supplement. | Drug: Pitavastatin and levothyroxine<br>* The initial dosage of pitavastatin is 2mg and the initial dosage of levothyroxine is 12.5ug. The dosage of levothyroxine will be regulated according to thyroid function test every 2-3 weeks. The regulation of pitavastatin dosage is same as the monotherapy group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of LDL-C levels | Absolute change value of serum LDL-C levels between the baseline and 6-month assessment. | Baseline and 6-month. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of non-LDL lipid levels (TC, TG, HDL-C, non-HDL-C) | Absolute change value of serum non-LDL lipid levels (including TC, TG, HDL-C, non-HDL-C) between the baseline and 6-month assessment. | Baseline and 6-month | 
| LDL-C control rate | Percentages of patients who had LDL-C values below the treatment goal (LDL-C<1.8mmol/L) at 1-, 2-, 3- and 6-month assessment. | Baseline and 1-, 2-, 3- and 6-month assessment. | 
| Dosage of treatment drugs (pitavastatin and levothyroxine) | The dosage of pitavastatin and levothyroxine in combination group at 6-month assessment; The dosage of pitavastatin in control group at 6-month assessment | At 6-month assessment. | 
| Levels of thyroid hormones at 6-month assessment | Levels of thyroid hormones (thyroid-stimulating hormone, free triiodothyronine, free thyroxine, total triiodothyronine, and total thyroxine) at 6-month assessment | At 6-month assessment. | 
| Rates of major adverse cardiac and cerebrovascular events at 6-month assessment | Rates of major adverse cardiac and cerebrovascular events (MACCE, including cardiac death, myocardial infarction, target vessel revascularization and cerebrovascular events) during 6 months follow-up. | During 6-month follow-up. | 
| Levels of glutamic-pyruvic transaminase (ALT) at 1-, 2-, 3- and 6-month assessment | Safety endpoint: live injury parameters, including levels of glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST). | Baseline and 1-, 2-, 3- and 6-month assessment. | 
| Levels of glutamic-oxaloacetic transaminase (AST) at 1-, 2-, 3- and 6-month assessment | Safety endpoint: live injury parameters, including levels of glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST). | Baseline and 1-, 2-, 3- and 6-month assessment. | 
| Levels of serum creatine kinase (CK) at 1-, 2-, 3- and 6-month assessment | Safety endpoint: muscle injury parameter--serum creatine kinase (CK) | Baseline and 1-, 2-, 3- and 6-month assessment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thyroid Hormone Replacement, Subclinical Hypothyroidism, Dyslipidemia, ASCVD, Statin