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

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

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).

Study Overview

• Status: Unknown
• Conditions: Dyslipidemia; Subclinical hypothyroïdism; ASCVD; Statin
• Intervention / Treatment: Drug: Pitavastatin and placebo; Drug: Pitavastatin and levothyroxine

• Study Type: Interventional
• Enrollment (Anticipated): 248
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chunli Shao, MD; Phone Number: 0086-10-88396171; Email: chunlishao@126.com
• Study Contact Backup: Name: Wenyao Wang, MD, PhD; Phone Number: 0086-10-88396173; Email: wwypumc@126.com

Study Locations

• China
  • Beijing, China, 100031
    • Recruiting
    • Fuwai Hospital, China National Center for Cardiovascular Diseases
    • Contact: Wenyao Wang, MD, PhD; Phone Number: 0086-10-88396171; Email: wwypumc@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant 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.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Shaochun.Li
• Collaborators: Beijing Friendship Hospital; Peking University Third Hospital; Xuanwu Hospital, Beijing; Beijing Chao Yang Hospital; Chinese Academy of Medical Sciences, Fuwai Hospital
• Investigators: Study Chair: Yi-Da Tang, MD, Fuwai Hospital, China National Center for Cardiovascular Diseases

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 25, 2019
• Primary Completion (Anticipated): February 28, 2020
• Study Completion (Anticipated): May 31, 2020

Study Registration Dates

• First Submitted: July 11, 2018
• First Submitted That Met QC Criteria: July 28, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): March 20, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Dyslipidemia; Statin; ASCVD; Thyroid Hormone Replacement; Subclinical Hypothyroidism
• Additional Relevant MeSH Terms: Metabolic Diseases; Endocrine System Diseases; Thyroid Diseases; Lipid Metabolism Disorders; Hypothyroidism; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pitavastatin
• Other Study ID Numbers: 2018-zx7

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No