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

Primary Purpose

Dyslipidemia, Subclinical hypothyroïdism, Statin

Status

Unknown status

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

Pitavastatin and placebo

Pitavastatin and levothyroxine

About this trial

This is an interventional treatment trial for Dyslipidemia focused on measuring Thyroid Hormone Replacement, Subclinical Hypothyroidism, Dyslipidemia, ASCVD, Statin

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Fuwai Hospital, China National Center for Cardiovascular DiseasesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Pivastatin and placebo

Pivastatin and LT-4

Arm Description

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

After randomization, patients in combination group will receive pitavastatin as the lipid-lowering therapy and take levothyroxine as the thyroid hormone supplement.

Outcomes

Primary Outcome Measures

Change of LDL-C levels

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)

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

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)

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

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

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

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

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

Safety endpoint: muscle injury parameter--serum creatine kinase (CK)

Full Information

NCT ID

NCT03606824

First Posted

July 11, 2018

Last Updated

March 18, 2019

Sponsor

Shaochun.Li

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT03606824

Brief Title

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

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Unknown status

Study Start Date

March 25, 2019 (Anticipated)

Primary Completion Date

February 28, 2020 (Anticipated)

Study Completion Date

May 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Shaochun.Li

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dyslipidemia, Subclinical hypothyroïdism, Statin, ASCVD

Keywords

Thyroid Hormone Replacement, Subclinical Hypothyroidism, Dyslipidemia, ASCVD, Statin

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

248 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pivastatin and placebo

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Pivastatin and LT-4

Arm Type

Experimental

Arm Description

After randomization, patients in combination group will receive pitavastatin as the lipid-lowering therapy and take levothyroxine as the thyroid hormone supplement.

Intervention Type

Drug

Intervention Name(s)

Pitavastatin and placebo

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Pitavastatin and levothyroxine

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change of LDL-C levels

Description

Absolute change value of serum LDL-C levels between the baseline and 6-month assessment.

Time Frame

Baseline and 6-month.

Secondary Outcome Measure Information:

Title

Changes of non-LDL lipid levels (TC, TG, HDL-C, non-HDL-C)

Description

Absolute change value of serum non-LDL lipid levels (including TC, TG, HDL-C, non-HDL-C) between the baseline and 6-month assessment.

Time Frame

Baseline and 6-month

Title

LDL-C control rate

Description

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.

Time Frame

Baseline and 1-, 2-, 3- and 6-month assessment.

Title

Dosage of treatment drugs (pitavastatin and levothyroxine)

Description

The dosage of pitavastatin and levothyroxine in combination group at 6-month assessment; The dosage of pitavastatin in control group at 6-month assessment

Time Frame

At 6-month assessment.

Title

Levels of thyroid hormones at 6-month assessment

Description

Levels of thyroid hormones (thyroid-stimulating hormone, free triiodothyronine, free thyroxine, total triiodothyronine, and total thyroxine) at 6-month assessment

Time Frame

At 6-month assessment.

Title

Rates of major adverse cardiac and cerebrovascular events at 6-month assessment

Description

Time Frame

During 6-month follow-up.

Title

Levels of glutamic-pyruvic transaminase (ALT) at 1-, 2-, 3- and 6-month assessment

Description

Safety endpoint: live injury parameters, including levels of glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST).

Time Frame

Baseline and 1-, 2-, 3- and 6-month assessment.

Title

Levels of glutamic-oxaloacetic transaminase (AST) at 1-, 2-, 3- and 6-month assessment

Description

Safety endpoint: live injury parameters, including levels of glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST).

Time Frame

Baseline and 1-, 2-, 3- and 6-month assessment.

Title

Levels of serum creatine kinase (CK) at 1-, 2-, 3- and 6-month assessment

Description

Safety endpoint: muscle injury parameter--serum creatine kinase (CK)

Time Frame

Baseline and 1-, 2-, 3- and 6-month assessment.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Chunli Shao, MD

Phone

0086-10-88396171

chunlishao@126.com

First Name & Middle Initial & Last Name or Official Title & Degree

Wenyao Wang, MD, PhD

Phone

0086-10-88396173

wwypumc@126.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yi-Da Tang, MD

Organizational Affiliation

Fuwai Hospital, China National Center for Cardiovascular Diseases

Official's Role

Study Chair

Facility Information:

Facility Name

Fuwai Hospital, China National Center for Cardiovascular Diseases

City

Beijing

ZIP/Postal Code

100031

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Wenyao Wang, MD, PhD

Phone

0086-10-88396171

wwypumc@126.com

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

20615126

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.

Results Reference

background

PubMed Identifier

11041458

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.

Results Reference

background

PubMed Identifier

7852521

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.

Results Reference

background

PubMed Identifier

18073305

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.

Results Reference

background

PubMed Identifier

18996793

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.

Results Reference

background

PubMed Identifier

24217672

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.

Results Reference

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

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