Safety and Efficacy of Empiric Levothyroxine (LT4) Dose Increase Versus Individualized LT4 Dose Increase in Hypothyroid Women During Pregnancy

NCT03115515 | Completed

• 1 other identifier: 2011-235
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

In women who require thyroid hormone replacement medication, the investigators will compare 2 ways to adjust thyroid medication during pregnancy to determine superiority in maintaining optimal blood levels of thyroid hormone. Thyroid hormone requirements increase significantly in pregnancy and it is important that blood levels of thyroid hormone remain normal so the fetus, which cannot make its own thyroid hormone has enough for early prenatal development. This trial compares 2 methods for adjusting thyroid medicine during pregnancy in women with known thyroid disease. Pregnant women (age 18 to 45) who take thyroid medication will be randomized to either 1) a 2-dose per week increase in thyroid medicine once pregnancy is confirmed, followed by dose adjustments every 2-4 weeks, or 2) adjustments in thyroid medication every 2-4 weeks in micrograms per day based on results of blood tests. The investigators will compare thyroid hormone levels throughout pregnancy between the groups of mothers to determine which method is superior in meeting the increased thyroid hormone requirements during pregnancy.

Conditions

Pregnancy Related; Thyroid

Keywords

Thyroid Stimulating Hormone

Outcome Measures

Primary Outcomes (1)

• % of TSH values within trimester-specific goal range per patient from study enrollment to delivery

  % of TSH values within trimester-specific goal range according to study group

  TSH will be assessed every 2 weeks from enrollment to 28 weeks gestation and then every 4 weeks from 29 weeks to delivery

Secondary Outcomes (3)

• Mean number of LT4 dose adjustment

  Dose adjustments will be assessed every 2 weeks from enrollment to 28 weeks gestation and then every 4 weeks from 29 weeks to delivery

• Mean number of LT4 dose adjustments by hypothyroidism etiology

  Dose adjustments will be assessed every 2 weeks from enrollment to 28 weeks gestation and then every 4 weeks from 29 weeks to delivery

• % of TSH values at goal according to anti-thyroid antibody status

  TSH will be assessed every 2 weeks from enrollment to 28 weeks gestation and then every 4 weeks from 29 weeks to delivery

Study Arms (2)

Adjustment in number of doses of thyroid hormone per week

EXPERIMENTAL

Patients in this group will increase pre-pregnancy thyroid hormone dose by 2 doses/week (extra dose on Wednesday and Saturday). Further dose adjustment are made every 2-4 weeks based on serum TSH, as shown below: * TSH\>10mIU/L, increase by 3 doses/week * TSH 5.0-9.9mIU/L, increase by 2 doses/week * TSH 2.0-4.9mIU/L, increase by 1 dose/week * TSH 0.4-1.9mIU/L, no change * TSH\<0.4mIU/L, decrease by 1 dose/week * TSH\<0.1mIU/L, decrease by 2 doses/week * Thyroid hormone dose will NOT be decreased due to TSH\<0.4mIU/L during the 1st trimester unless patient also has elevated circulating T4 and/or T3 levels, indicate of true hyperthyroidism.

Drug: levothyroxine

Adjustment in micrograms per day of thyroid hormone

EXPERIMENTAL

Patients in this group adjust thyroid hormone dose based on Visit 1 TSH and pre-pregnancy thyroid hormone dose. Further dose adjustments are made every 2-4 weeks based on serum TSH, as shown below: * TSH\>10mIU/L, increase dose by 50mcg/day if dose \<125mcg/day or increase by 75mcg/day if dose \>125mcg * TSH 5.0-9.9mIU/L, increase dose by 25mcg/day if dose \<125mcg/day or increase by 50mcg/day if dose \>125mcg * TSH 2.0-4.9mIU/L, increase dose by 12.5mcg/day if dose \<125mcg/day or increase by 25mcg/day if dose \>125mcg * TSH 0.4-1.9mIU/L, no change * TSH\<0.4mIU/L, decrease dose by 12.5mcg/day if dose \<125mcg/day or decrease by 25mcg/day if dose \>125mcg/day * TSH\<0.1mIU/L, decrease dose by 25mcg/day if dose \<125mcg/day or decrease by 50mcg/day if dose \>125mcg/day * Thyroid hormone dose will NOT be decreased due to TSH\<0.4mIU/L during the 1st trimester unless patient also has elevated circulating T4 and/or T3 levels, indicate of true hyperthyroidism.

Drug: levothyroxine

Interventions

levothyroxine DRUG

To compare two different methods of adjusting thyroid hormone replacement during pregnancy to maintain TSH within the normal reference range for pregnancy.

Also known as: Synthroid, Levoxyl

Adjustment in micrograms per day of thyroid hormone; Adjustment in number of doses of thyroid hormone per week

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female between ages of 18-45 who takes thyroid hormone replacement medicine AND pregnant or plan to become pregnant in the near future.

You may not qualify if:

• Males
• Younger than 18 or older than 45 years old
• More than 10 weeks pregnant at enrollment
• Iodine deficient
• Pregnant with more than one baby (i.e., twins, triplets, etc.)
• NOT taking thyroid hormone medicine before becoming pregnant
• Levels of thyroid hormone in blood have been too low or too high in the past 6 months
• Treated with radioactive iodine in the past year.

Sponsors & Collaborators

• Medstar Health Research Institute: lead

Study Sites (1)

Medstar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (1)

• Sullivan SD, Downs E, Popoveniuc G, Zeymo A, Jonklaas J, Burman KD. Randomized Trial Comparing Two Algorithms for Levothyroxine Dose Adjustment in Pregnant Women With Primary Hypothyroidism. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3499-3507. doi: 10.1210/jc.2017-01086.

  PMID: 28911144 DERIVED

MeSH Terms

Conditions

Thyroid Diseases

Interventions

Thyroxine

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 7, 2017
• First Posted: April 14, 2017
• Study Start: August 1, 2011
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: March 29, 2018

Record last verified: 2018-03

Locations

US (1)