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

Sponsor

Shaochun.Li (Other)

Overall Status

Unknown status

CT.gov ID

NCT03606824

Collaborator

Chinese Academy of Medical Sciences, Fuwai Hospital (Other), Peking University Third Hospital (Other), Beijing Chao Yang Hospital (Other), Xuanwu Hospital, Beijing (Other), Beijing Friendship Hospital (Other)

248

Enrollment

Location

Arms

14.2

Anticipated Duration (Months)

17.4

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Dyslipidemia Subclinical hypothyroïdism Statin ASCVD	Drug: Pitavastatin and placebo Drug: Pitavastatin and levothyroxine	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

248 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Mar 25, 2019

Anticipated Primary Completion Date :

Feb 28, 2020

Anticipated Study Completion Date :

May 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Pivastatin and placebo After randomization, patients in Pivastatin + placebo group will receive pitavastatin and placebo.	Drug: Pitavastatin and placebo 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.
Experimental: Pivastatin and LT-4 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 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.

Arm

Intervention/Treatment

Placebo Comparator: Pivastatin and placebo

After randomization, patients in Pivastatin + placebo group will receive pitavastatin and placebo.

Drug: Pitavastatin and placebo

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.

Experimental: Pivastatin and LT-4

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

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.

Outcome Measures

Primary Outcome Measures

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

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.
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).
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.