Clinical trial NCT06999278: LIGHT Trial: Levothyroxine for Gestational Hypothyroidism in Recurrent Pregnancy Loss
Official title: LIGHT - Levothyroxine for Isolated Gestational HypoThyroidism in Women With Recurrent Pregnancy Loss: a Multicenter Randomized, Double-blind, Placebo-controlled Trial - a Study Protocol
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Abortion, Habitual
Keywords: recurrent pregnancy loss
isolated maternal hypothyroidism
levothyroxine
adverse pregnancy outcomes
live birth
neonatal complications
Lead sponsor: Women's Hospital School Of Medicine Zhejiang University
Sponsor class: OTHER
Collaborators: name: Zhejiang Provincial People's Hospital
First posted: 2025-05-31
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multi-center, randomized, double-blind, placebo-controlled trial
Primary purpose: TREATMENT

Brief summary: The goal of this randomized, double-blind, placebo-controlled clinical trial is to evaluate whether levothyroxine supplement improves pregnancy outcomes in women with recurrent pregnancy loss (RPL) and isolated maternal hypothyroidism (IMH).

The main questions it aims to answer are:

Does levothyroxine increase the live birth rate after 24 weeks of gestation? Does levothyroxine improve secondary outcomes such as ongoing pregnancy rates, reduce the incidence of pregnancy loss, or influence maternal and neonatal complications?

Researchers will:

Compare the levothyroxine treatment group (50 µg/day) to the placebo group to assess the impact of the intervention on live birth rates and other pregnancy outcomes.

Participants will:

Be randomly assigned to receive either levothyroxine or a placebo. Take the assigned treatment daily starting from enrollment until the end of pregnancy.

Undergo routine follow-up visits to monitor pregnancy progress and outcomes. This trial seeks to determine whether routine levothyroxine supplementation can improve pregnancy outcomes for women with RPL and IMH.

Detailed description: Investigators will perform a multi-center, randomized, placebo, double-blind clinical trial of levothyroxine (LT4) in patients aged between 18 years and 40 yearls who are diagnosed with isolated hypothyroxemia (defined as lower FT4 level with normal TSH) and have a previous history of recurrent miscarriages (defined as two or more pregnancy loss). Investigators will assess the effects of standard dose of 50ug/d levothyroxine therapy from the day after randomization to the day of delivery on the pregnancy outcomes, including live birth, neonatal complications, and adverse pregnancy outcomes, etc.

Eligibility criteria: Inclusion Criteria:

* women with singleton pregnancy
* women with a history of recurrent pregnancy loss (defined as two or more pregnancy loss before 20wks)
* women diagnosed with isolated maternal hypothyroidism (defined as isolated lower level of FT4 with normal TSH levels) in the current pregnancy before 20wks

Exclusion Criteria:

* patients with known thyroid disorders
* patients with antiphospholipid syndrome or other autoimmune conditions
* patients with contraindications to levothyroxine (e.g., acute cardiac arrest, acute pancreatitis, acute myocarditis)
* patients attending other ongoing clinical trials or unwilling to participate.

Primary outcomes:
measure: Live birth after 28 weeks of gestation
timeFrame: From the enrollment to the day of delivery after 28+0 weeks of gestation
Secondary outcomes:
measure: Ongoing pregnancy at 7 weeks of gestation
timeFrame: From the day of randomization to the 7 weeks of gestation
measure: Ongoing pregnancy at 12 weeks of gestation
timeFrame: From the day of randomization to the 12 weeks of gestation
measure: Ongoing pregnancy at 24 weeks of gestation
timeFrame: From the day of randomization to the 24 weeks of gestation
measure: Miscarriage
timeFrame: From enrollment to 19+6 weeks of gestation
measure: Stillbirth
timeFrame: From enrollment to the day of delivery of the dead fetus from 20+0 weeks onward
measure: Ectopic pregnancy
timeFrame: From enrollment to the end of treatment up to 20 weeks
measure: Abortion
timeFrame: From enrollment to the day of termination of pregnancy up to 27+6 weeks
measure: Need for cervical cerclage
timeFrame: From enrollment to the day of cervical cerlage performed up to 27+6 weeks
measure: Preterm birth
timeFrame: From enrollment to the day of preterm birth between 28+0 and 36+6 weeks
measure: Gestational age at delivery
timeFrame: up to delivery
measure: Antepartum complications
timeFrame: From enrollment to the day of delivery, up to 42+0 weeks
measure: Intrapartum complications
timeFrame: up to delivery
measure: Postpartum complications
timeFrame: up to 42 days after childbirth
measure: Neonatal birthweight
timeFrame: up to delivery
measure: Neonatal APGAR score
timeFrame: up to 5 minutes after delivery
measure: Neonatal complications
timeFrame: up to 7 days after delivery
Other outcomes:
measure: Adverse outcomes related to levothyroxine treatment
timeFrame: From enrollment to the end of treatment, up to 40 weeks
Locations:
city: HangZhou
country: China
facility: Zhejiang Women's Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang People's Hospital
state: Zhejiang
Study officials:
affiliation: luoq@zju.edu.cn
name: Qiong Luo, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dhillon-Smith RK, Middleton LJ, Sunner KK, Cheed V, Baker K, Farrell-Carver S, Bender-Atik R, Agrawal R, Bhatia K, Edi-Osagie E, Ghobara T, Gupta P, Jurkovic D, Khalaf Y, MacLean M, McCabe C, Mulbagal K, Nunes N, Overton C, Quenby S, Rai R, Raine-Fenning N, Robinson L, Ross J, Sizer A, Small R, Tan A, Underwood M, Kilby MD, Boelaert K, Daniels J, Thangaratinam S, Chan SY, Coomarasamy A. Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception. N Engl J Med. 2019 Apr 4;380(14):1316-1325. doi: 10.1056/NEJMoa1812537. Epub 2019 Mar 23.
citation: van Dijk MM, Vissenberg R, Fliers E, van der Post JAM, van der Hoorn MP, de Weerd S, Kuchenbecker WK, Hoek A, Sikkema JM, Verhoeve HR, Broeze KA, de Koning CH, Verpoest W, Christiansen OB, Koks C, de Bruin JP, Papatsonis DNM, Torrance H, van Wely M, Bisschop PH, Goddijn M. Levothyroxine in euthyroid thyroid peroxidase antibody positive women with recurrent pregnancy loss (T4LIFE trial): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2022 May;10(5):322-329. doi: 10.1016/S2213-8587(22)00045-6. Epub 2022 Mar 14.