Clinical trial NCT03606824: Thyroid Hormone Replacement for Subclinical Hypothyroidism and Dyslipidemia in ASCVD (ThyroHeart-Lipid Study)
Official title: Thyroid Hormone Replacement for Subclinical Hypothyroidism and Dyslipidemia in Patients With Atherosclerotic Cardiovascular Diseases (ThyroHeart-Lipid Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Dyslipidemia
Subclinical hypothyroïdism
Statin
ASCVD
Keywords: Thyroid Hormone Replacement
Subclinical Hypothyroidism
Dyslipidemia
ASCVD
Statin
Lead sponsor: China National Center for Cardiovascular Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Peking University Third Hospital
name: Beijing Chao Yang Hospital
name: Xuanwu Hospital, Beijing
name: Beijing Friendship Hospital
First posted: 2018-07-31
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Change of LDL-C levels
timeFrame: Baseline and 6-month.
Secondary outcomes:
measure: Changes of non-LDL lipid levels (TC, TG, HDL-C, non-HDL-C)
timeFrame: Baseline and 6-month
measure: LDL-C control rate
timeFrame: Baseline and 1-, 2-, 3- and 6-month assessment.
measure: Dosage of treatment drugs (pitavastatin and levothyroxine)
timeFrame: At 6-month assessment.
measure: Levels of thyroid hormones at 6-month assessment
timeFrame: At 6-month assessment.
measure: Rates of major adverse cardiac and cerebrovascular events at 6-month assessment
timeFrame: During 6-month follow-up.
measure: Levels of glutamic-pyruvic transaminase (ALT) at 1-, 2-, 3- and 6-month assessment
timeFrame: Baseline and 1-, 2-, 3- and 6-month assessment.
measure: Levels of glutamic-oxaloacetic transaminase (AST) at 1-, 2-, 3- and 6-month assessment
timeFrame: Baseline and 1-, 2-, 3- and 6-month assessment.
measure: Levels of serum creatine kinase (CK) at 1-, 2-, 3- and 6-month assessment
timeFrame: Baseline and 1-, 2-, 3- and 6-month assessment.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fuwai Hospital, China National Center for Cardiovascular Diseases
Study officials:
affiliation: Fuwai Hospital, China National Center for Cardiovascular Diseases
name: Yi-Da Tang, MD
role: STUDY_CHAIR
References:
citation: Gjedde S, Gormsen LC, Rungby J, Nielsen S, Jorgensen JO, Pedersen SB, Riis AL, Weeke J, Moller N. Decreased lipid intermediate levels and lipid oxidation rates despite normal lipolysis in patients with hypothyroidism. Thyroid. 2010 Aug;20(8):843-9. doi: 10.1089/thy.2009.0212.
citation: Tzotzas T, Krassas GE, Konstantinidis T, Bougoulia M. Changes in lipoprotein(a) levels in overt and subclinical hypothyroidism before and during treatment. Thyroid. 2000 Sep;10(9):803-8. doi: 10.1089/thy.2000.10.803.
citation: Pazos F, Alvarez JJ, Rubies-Prat J, Varela C, Lasuncion MA. Long-term thyroid replacement therapy and levels of lipoprotein(a) and other lipoproteins. J Clin Endocrinol Metab. 1995 Feb;80(2):562-6. doi: 10.1210/jcem.80.2.7852521.
citation: Pearce EN, Wilson PW, Yang Q, Vasan RS, Braverman LE. Thyroid function and lipid subparticle sizes in patients with short-term hypothyroidism and a population-based cohort. J Clin Endocrinol Metab. 2008 Mar;93(3):888-94. doi: 10.1210/jc.2007-1987. Epub 2007 Dec 11.
citation: Lando HM, Burman KD. Two cases of statin-induced myopathy caused by induced hypothyroidism. Endocr Pract. 2008 Sep;14(6):726-31. doi: 10.4158/EP.14.6.726.
citation: Willard DL, Leung AM, Pearce EN. Thyroid function testing in patients with newly diagnosed hyperlipidemia. JAMA Intern Med. 2014 Feb 1;174(2):287-9. doi: 10.1001/jamainternmed.2013.12188. No abstract available.