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

NCT06653907 | Not Yet Recruiting Phase 4

• 2 other identifiers: 202300992021CR29
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

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

Keywords

TSH; TPOAb; pregnant women; levothyroxine; outcome

Outcome Measures

Primary Outcomes (1)

• Rate of fetal loss

  * Abortion: Ultrasound examination shows no embryo sac or only empty sac, no fetal heart or bud development. * Intrauterine fetal death: Fetal death in utero at 20 weeks or more of pregnancy. * Stillbirth: Death at birth over 28 weeks of pregnancy. * Neonatal death: Newborns die within 7 days.

  From enrollment to the end of treatment at 40 weeks

Secondary Outcomes (18)

• Fetal loss rates and reasons within 12 weeks of pregnancy.

  From enrollment to the end of treatment at 12 weeks

• Fetal loss rates and reasons within 24 weeks of pregnancy.

  From enrollment to the end of treatment at 24 weeks

• Fetal loss rates and reasons within 28 weeks of pregnancy.

  From enrollment to the end of treatment at 28 weeks

• Fetal loss rates and reasons within 34 weeks of pregnancy.

  From enrollment to the end of treatment at 34 weeks

• Rate of cesarean section

  From enrollment to the end of treatment at 40 weeks

Other Outcomes (3)

• Adverse events (AEs)

  From enrollment to the end of treatment at 40 weeks

• Serious adverse events (SAEs)

  From enrollment to the end of treatment at 40 weeks

• Thyrotoxicosis

  From enrollment to the end of treatment at 40 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Levothyroxine

ACTIVE COMPARATOR

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.

Drug: Levothyroxine Sodium (LT4) Tablets

Interventions

Levothyroxine Sodium (LT4) Tablets 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.

Levothyroxine

Placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women of childbearing age（18-45 years old）, natural pregnancy, singleton pregnancy.
• Measure thyroid related indexes within 8 weeks of pregnancy: TSH 2.5mIU/L-ULRR, FT4 is normal and TPOAb negativity.
• Willing to sign an informed consent form.

You may not qualify if:

• History of recurrent miscarriage (≥3 times).
• Assisted reproduction (artificial insemination, in vitro fertilization and embryo transfer);
• Suffer from diseases that seriously affect pregnancy outcome, including hypertension, diabetes, heart disease, liver and kidney dysfunction, etc.
• Failure of vital organs.
• Except autoimmune thyroid disease，suffer from other autoimmune diseases.
• 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.).
• 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.)
• Secondary hypothyroidism or central hypothyroidism. (Including pituitary tumors, surgery, radiotherapy, lymphocytic hypophysitis, etc.)
• L-T4 allergy.
• Unwilling to sign an informed consent.
• Other clinicians judged that they are not suitable to participate in the study.

Sponsors & Collaborators

• Yang ZHANG: lead
• National Research Institute for Family Planning, China: collaborator
• The Fourth Hospital of Shijiazhuang: collaborator

Study Sites (1)

Fourth hospital of Shijiazhuang city

Shijiazhuang, Heibei, 050011, China

Location

MeSH Terms

Conditions

Thyroid Diseases

Interventions

Thyroxine; Tablets

Condition Hierarchy (Ancestors)

Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Ying Gao, Professor

  Endocrinology Department of Peking University First Hospital

  STUDY CHAIR

Central Study Contacts

Yang Zhang, Doctor

CONTACT

008601083575103; emilyzy14@sina.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associated chief of the endocrinology department of peking university first hospital

Study Record Dates

• First Submitted: October 14, 2024
• First Posted: October 22, 2024
• Study Start: October 25, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): October 31, 2027
• Last Updated: October 23, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: IPD will be available half year after the last participants finished the study

Locations

CN (1)