Levothyroxine Intervention in Pregnant Women with TSH （2.5 MIU/L-upper Limit of Reference Range） and Negative Thyroid Peroxidase Antibody

NCT ID: NCT06653907

Last Updated: 2024-10-23

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-25
• Study Completion Date: 2027-10-31

Brief Summary

The goal of this clinical trial is to learn if levothyroxine (L-T4) works to treat pregnant women with TSH 2.5 mIU/L-the upper limit of reference range (ULRR) of pregnancy and TPOAb-negative. It will also learn about the safety of L-T4. The main quesitons the investigator want to answer are:

• Will L-T4 reduce miscarriage rates and have an impact on pregnancy complications in pregnant participants?
• What medical issues do participants have when taking L-T4 during pregnancy? -Investigators will compare L-T4 with placebo (a substance with a similar appearance without medication) to see if L-T4 could reduce miscarriage rates

Participants should:

• Take L-T4 or placebo during the whole pregnancy.
• Visit the hospital once every 6-8 weeks during pregnancy for checkups and tests
• Keep a diary of their pregncny complications and daily record of L-T4 or placebo intake.
• Visit the hospital for examination 42 days postpartum for checkups and follow up by phone at 6 and 12 months postpartum.

Conditions

Thyroid Abnormalities; Pregnant Woman; Pregnancy Outcomes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

The target participants are women who undergo thyroid function and TPOAb testing in early pregnancy. Among these pregnant women, TSH 2.5mIU/L-ULRR and TPOAb negative pregnant women will be selected. Then, participants were randomly assigned 1:1 (based on age and BMI) to an oral placebo group during pregnancy. Participants in our study will determine the dosage of medication based on their weight.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants in our study will determine the dosage of placebo based on their weight (BW):

1. BW ≥50kg: Starting with a daily dose of 1 tablet;

2. BW < 50kg: Starting with a daily dose of half a tablet.

At 12 weeks, 18-20 weeks, 24-26 weeks, and 34-36 weeks of gestation, the serum TSH, FT3, and FT4 will be measured, and investigator will adjust dosage according to TSH:

1. When TSH > ULRR, the participants will receive L-T4 in addition to their original medication, and additional unplanned follow-up;

2. When TSH at 2.5mIU/L-ULRR, add 1/4 tablet of medictaion;

3. When TSH at LLRR -2.5mIU/L, maintain the original dose;

4. When TSH <LLRR, reduce 1/4 tablets of medictaion.

5. If TSH continues to be lower than LLRR after discontinuation, investigator will measure FT4, TRAb and other indicators to determine if it is clinical hyperthyroidism. If so, antithyroid drugs will administered according to guidelines. Participants will stop all trial medictaion after delivery.

Levothyroxine

The target participants are women who undergo thyroid function and TPOAb testing in early pregnancy. Among these pregnant women, TSH 2.5mIU/L-ULRR and TPOAb negative pregnant women will be selected. Then, participants were randomly assigned 1:1 (based on age and BMI) to an active comparator group of oral Levothyroxine (L-T4) during pregnancy. Participants in our study will determine the dosage of medication based on their weight.

Group Type: ACTIVE_COMPARATOR

Levothyroxine Sodium (LT4) Tablets

Intervention Type: DRUG

Participants in our study will determine the dosage of L-T4 based on their weight (BW):

1. BW ≥50kg: Starting with a daily dose of 1 tablet;

2. BW < 50kg: Starting with a daily dose of half a tablet.

At 12 weeks, 18-20 weeks, 24-26 weeks, and 34-36 weeks of gestation, the serum TSH, FT3, and FT4 will be measured, and investigator will adjust dosage according to TSH:

1. When TSH > ULRR, the participants will receive L-T4 in addition to their original medication, and additional unplanned follow-up;

2. When TSH at 2.5mIU/L-ULRR, add 1/4 tablet of medictaion;

3. When TSH at LLRR -2.5mIU/L, maintain the original dose;

4. When TSH <LLRR, reduce 1/4 tablets of medictaion.

5. If TSH continues to be lower than LLRR after discontinuation, investigator will measure FT4, TRAb and other indicators to determine if it is clinical hyperthyroidism. If so, antithyroid drugs will administered according to guidelines. Participants will stop all trial medictaion after delivery.

Interventions

Levothyroxine Sodium (LT4) Tablets

Participants in our study will determine the dosage of L-T4 based on their weight (BW):

1. BW ≥50kg: Starting with a daily dose of 1 tablet;

2. BW < 50kg: Starting with a daily dose of half a tablet.

At 12 weeks, 18-20 weeks, 24-26 weeks, and 34-36 weeks of gestation, the serum TSH, FT3, and FT4 will be measured, and investigator will adjust dosage according to TSH:

1. When TSH > ULRR, the participants will receive L-T4 in addition to their original medication, and additional unplanned follow-up;

2. When TSH at 2.5mIU/L-ULRR, add 1/4 tablet of medictaion;

3. When TSH at LLRR -2.5mIU/L, maintain the original dose;

4. When TSH <LLRR, reduce 1/4 tablets of medictaion.

5. If TSH continues to be lower than LLRR after discontinuation, investigator will measure FT4, TRAb and other indicators to determine if it is clinical hyperthyroidism. If so, antithyroid drugs will administered according to guidelines. Participants will stop all trial medictaion after delivery.

Intervention Type: DRUG

Placebo

Participants in our study will determine the dosage of placebo based on their weight (BW):

1. BW ≥50kg: Starting with a daily dose of 1 tablet;

2. BW < 50kg: Starting with a daily dose of half a tablet.

At 12 weeks, 18-20 weeks, 24-26 weeks, and 34-36 weeks of gestation, the serum TSH, FT3, and FT4 will be measured, and investigator will adjust dosage according to TSH:

1. When TSH > ULRR, the participants will receive L-T4 in addition to their original medication, and additional unplanned follow-up;

2. When TSH at 2.5mIU/L-ULRR, add 1/4 tablet of medictaion;

3. When TSH at LLRR -2.5mIU/L, maintain the original dose;

4. When TSH <LLRR, reduce 1/4 tablets of medictaion.

5. If TSH continues to be lower than LLRR after discontinuation, investigator will measure FT4, TRAb and other indicators to determine if it is clinical hyperthyroidism. If so, antithyroid drugs will administered according to guidelines. Participants will stop all trial medictaion after delivery.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Women of childbearing age（18-45 years old）, natural pregnancy, singleton pregnancy.

2. Measure thyroid related indexes within 8 weeks of pregnancy: TSH 2.5mIU/L-ULRR, FT4 is normal and TPOAb negativity.

3. Willing to sign an informed consent form.

Exclusion Criteria

1. History of recurrent miscarriage (≥3 times).

2. Assisted reproduction (artificial insemination, in vitro fertilization and embryo transfer);

3. Suffer from diseases that seriously affect pregnancy outcome, including hypertension, diabetes, heart disease, liver and kidney dysfunction, etc.

4. Failure of vital organs.

5. Except autoimmune thyroid disease，suffer from other autoimmune diseases.

6. Thyroid diseases (including hyperthyroidism, thyroid cancer, thyroid amyloidosis and other extensive intrathyroidal diseases, current subacute thyroiditis, iodine-deficiency endemic goiter, thyroidectomy or 131I treatment, previous thyroid Ultrasound prompts diffuse thyroid disease, etc.).

7. Use of thyroid-related drugs (lithium carbonate, thioureas, sulfonamides, sodium para-amino salicylate, potassium perchlorate, phenylbutazone, sulfate, tyrosine kinase inhibitor, etc.) during screening and affect thyroid Functional testing drugs. (Including glucocorticoids, metoclopramide, propranolol, amiodarone, sodium valproate, etc.)

8. Secondary hypothyroidism or central hypothyroidism. (Including pituitary tumors, surgery, radiotherapy, lymphocytic hypophysitis, etc.)

9. L-T4 allergy.

10. Unwilling to sign an informed consent.

11. Other clinicians judged that they are not suitable to participate in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Research Institute for Family Planning, China

OTHER_GOV

Sponsor Role: collaborator

The Fourth Hospital of Shijiazhuang

OTHER

Sponsor Role: collaborator

Yang ZHANG

OTHER

Sponsor Role: lead

Responsible Party

Yang ZHANG

Associated chief of the endocrinology department of peking university first hospital

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ying Gao, Professor

Role: STUDY_CHAIR

Endocrinology Department of Peking University First Hospital

Locations

Fourth hospital of Shijiazhuang city

Shijiazhuang, Heibei, China

Countries

China

Central Contacts

Yang Zhang, Doctor

Role: CONTACT

emilyzy14@sina.com

008601083575103

Facility Contacts

Guohua Zhang, Professor

Role: primary

zghh_456@163.com

0086031189927628

Other Identifiers

2021CR29

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

20230099

Identifier Type: -

Identifier Source: org_study_id