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

Official title

Randomized Control Study of Levothyroxine Intervention in Pregnant Women with Thyroid Stimulating Hormone Between 2.5 MIU/L and Upper Limit of Reference Range and Negative Thyroid Peroxidase Antibody

Overview

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.

Interventions

• Drug 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 foll
• 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 f

Primary outcome measures

• Rate of fetal loss [Time frame: From enrollment to the end of treatment at 40 weeks]

Secondary outcome measures (12)

• Fetal loss rates and reasons within 12 weeks of pregnancy. [Time frame: From enrollment to the end of treatment at 12 weeks]
• Fetal loss rates and reasons within 24 weeks of pregnancy. [Time frame: From enrollment to the end of treatment at 24 weeks]
• Fetal loss rates and reasons within 28 weeks of pregnancy. [Time frame: From enrollment to the end of treatment at 28 weeks]
• Fetal loss rates and reasons within 34 weeks of pregnancy. [Time frame: From enrollment to the end of treatment at 34 weeks]
• Rate of cesarean section [Time frame: From enrollment to the end of treatment at 40 weeks]
• Gestational week of delivery [Time frame: From enrollment to the end of treatment at 40 weeks]
• Number of Participants requiring treatments for preventing miscarriage [Time frame: From enrollment to the end of treatment at 40 weeks]
• Rate of hyperemesis gravidarum [Time frame: From enrollment to the end of treatment at 40 weeks]
• Rate of gestational diabetes [Time frame: From enrollment to the end of treatment at 40 weeks]
• Rate of hypertensive disorders of pregnancy [Time frame: From enrollment to the end of treatment at 40 weeks]
• Rate of early preterm delivery [Time frame: From enrollment to the end of treatment at 34 weeks]
• Rate of late preterm delivery [Time frame: From enrollment to the end of treatment at 37 weeks]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Fourth hospital of Shijiazhuang city — Shijiazhuang

Identifiers

NCT: NCT06653907 · 20230099 · 2021CR29

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗