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

Not Applicable

• Conditions: Subclinical hypothyroïdism; Statin; Dyslipidemia; ASCVD
• Interventions: Drug: Pitavastatin and levothyroxine; Drug: Pitavastatin and placebo

• Registration Number: NCT03606824
• Lead Sponsor: Shaochun.Li

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-07-11
• Study First Submitted QC: 2018-07-28
• Study First Posted: 2018-07-31
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-18
• Last Update Posted: 2019-03-20
• Study Start: 2019-03-25
• Primary Completion: 2020-02-28
• Study Completion: 2020-05-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 248

Inclusion Criteria

1. Male or non-pregnant female;
2. Stable or unstable angina with evidence of myocardial ischemia; coronary angiography reveals stenosis lesions;
3. Subclinical hypothyroidism defined as mild TSH elevation within 5-10mIU/L and normal serum thyroid hormone levels within reference ranges;
4. Level of LDL-C is more than 1.8mmol/L before randomization.
5. Participate in the trial voluntarily and signs the written informed consent form.

Exclusion Criteria

1. Those who have participated in other drug or therapy equipment clinical trials but did not reach the main study endpoint time limit;
2. Symptoms of severe heart failure (NYHA Class III and above) or left ventricular ejection fraction < 40% (ultrasound or left ventricle ngiography);
3. Pregnant or lactating women;
4. 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.
5. Patients who are unable to withstand lipid-lowering therapy or thyroid hormone replacement due to allergy to statins or levothyroxine;
6. Serum AST/ALT is three times higher than the upper limits of normal.
7. Patient's life expectancy is less than 12 months;
8. Those waiting for heart transplantation;
9. Patients who are deemed by the researchers to have low compliance and unable to abide by the requirements and complete the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pivastatin and LT-4	Pitavastatin and levothyroxine	After randomization, patients in combination group will receive pitavastatin as the lipid-lowering therapy and take levothyroxine as the thyroid hormone supplement.
Pivastatin and placebo	Pitavastatin and placebo	After randomization, patients in Pivastatin + placebo group will receive pitavastatin and placebo.

Primary Outcome Measures

Name	Time	Method
Change of LDL-C levels	Baseline and 6-month.	Absolute change value of serum LDL-C levels between the baseline and 6-month assessment.

Secondary Outcome Measures

Name	Time	Method
Levels of glutamic-oxaloacetic transaminase (AST) at 1-, 2-, 3- and 6-month assessment	Baseline and 1-, 2-, 3- and 6-month assessment.	Safety endpoint: live injury parameters, including levels of glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST).
Levels of serum creatine kinase (CK) at 1-, 2-, 3- and 6-month assessment	Baseline and 1-, 2-, 3- and 6-month assessment.	Safety endpoint: muscle injury parameter--serum creatine kinase (CK)
Dosage of treatment drugs (pitavastatin and levothyroxine)	At 6-month assessment.	The dosage of pitavastatin and levothyroxine in combination group at 6-month assessment; The dosage of pitavastatin in control group at 6-month assessment
Levels of thyroid hormones at 6-month assessment	At 6-month assessment.	Levels of thyroid hormones (thyroid-stimulating hormone, free triiodothyronine, free thyroxine, total triiodothyronine, and total thyroxine) at 6-month assessment
Rates of major adverse cardiac and cerebrovascular events at 6-month assessment	During 6-month follow-up.	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.
Levels of glutamic-pyruvic transaminase (ALT) at 1-, 2-, 3- and 6-month assessment	Baseline and 1-, 2-, 3- and 6-month assessment.	Safety endpoint: live injury parameters, including levels of glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST).
Changes of non-LDL lipid levels (TC, TG, HDL-C, non-HDL-C)	Baseline and 6-month	Absolute change value of serum non-LDL lipid levels (including TC, TG, HDL-C, non-HDL-C) between the baseline and 6-month assessment.
LDL-C control rate	Baseline and 1-, 2-, 3- and 6-month assessment.	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.

Trial Locations

Locations (1)

Fuwai Hospital, China National Center for Cardiovascular Diseases; 🇨🇳 Beijing, China