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| Name | Class |
|---|---|
| Zhejiang Provincial People's Hospital | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm LT4 | Experimental | The intervention will consist of standard treatment with levothyroxine tablets (50ug/day). The treatment will start from the next day after randomization and end at the day of delivery. |
|
| Arm Placebo | Placebo Comparator | The intervention will consist of standard treatment with levothyroxine placebo daily. The treatment will start from the next day after randomization and end at the day of delivery. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Levothyroxin | Drug | Levothyroxin 50ug/d from randomization until delivery |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Live birth after 28 weeks of gestation | Live birth following spontaneous labor or iatrogenic delivery after 28+0 weeks of gestation (196 days from the participant's last menstrual period) | From the enrollment to the day of delivery after 28+0 weeks of gestation |
| Measure | Description | Time Frame |
|---|---|---|
| Ongoing pregnancy at 7 weeks of gestation | ultrasound diagnosis of ongoing pregnancy at 7 weeks of gestation | From the day of randomization to the 7 weeks of gestation |
| Ongoing pregnancy at 12 weeks of gestation |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse outcomes related to levothyroxine treatment | unexpected medical event in a patient or clinical trial participant receiving a pharmaceutical product, which may not necessarily be causally related to the treatment | From enrollment to the end of treatment, up to 40 weeks |
Inclusion Criteria:
Exclusion Criteria:
Women diagnosed with confirmed pregnancy
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Qiong Luo, Ph.D. | Contact | +86 571 89998819 | luoq@zju.edu.cn | |
| Zixing Zhong, MSc | Contact | +86 571 85893328 | zhongzixing@hmc.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Qiong Luo, Ph.D. | luoq@zju.edu.cn | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zhejiang Women's Hospital | Hangzhou | Zhejiang | 310006 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30907987 | Background | 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. | |
| 35298917 |
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individual participant data may be made available at reasonable request on the principal investigator.
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| ID | Term |
|---|---|
| D000026 | Abortion, Habitual |
| ID | Term |
|---|---|
| D000022 | Abortion, Spontaneous |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D013974 | Thyroxine |
| ID | Term |
|---|---|
| D013963 | Thyroid Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D024322 | Amino Acids, Aromatic |
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This is a multi-center, randomized, double-blind, placebo-controlled trial
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Participants and Investigators Both participants and investigators are blinded to the group assignments. Participants receive either levothyroxine (50 µg/day) or a placebo in identical tablets that are indistinguishable in appearance, color, shape, and weight. Investigators administering treatments and assessing outcomes remain unaware of the treatment allocation.
Randomization and Allocation Randomization is conducted using a secure web-based system, ensuring a 1:1 allocation ratio to either the levothyroxine or placebo group. The randomization process is stratified by study centers to maintain balance across locations.
Packaging and Labeling Study drugs, including the placebo, are packaged and labeled uniformly to prevent any visual or informational clues. Each package contains a unique identification code that corresponds to the randomization list, ensuring proper allocation without revealing the treatment group.
| Placebo |
| Drug |
Placebo to levothyroxin |
|
ultrasound diagnosis of ongoing pregnancy at 12 weeks of gestation
| From the day of randomization to the 12 weeks of gestation |
| Ongoing pregnancy at 24 weeks of gestation | ultrasound diagnosis of ongoing pregnancy at 24 weeks of gestation | From the day of randomization to the 24 weeks of gestation |
| Miscarriage | pregnancy loss before 20 weeks of gestation | From enrollment to 19+6 weeks of gestation |
| Stillbirth | fetal death delivered beyond 20 weeks of gestation | From enrollment to the day of delivery of the dead fetus from 20+0 weeks onward |
| Ectopic pregnancy | ultrasound diagnosis of ectopic pregnancy | From enrollment to the end of treatment up to 20 weeks |
| Abortion | personal request the termination of pregnancy without medical conditions | From enrollment to the day of termination of pregnancy up to 27+6 weeks |
| Need for cervical cerclage | medically indicated cervical cerclage up to 27+6 weeks of gestation | From enrollment to the day of cervical cerlage performed up to 27+6 weeks |
| Preterm birth | live birth between 28+0 and 36+6 weeks of gestation | From enrollment to the day of preterm birth between 28+0 and 36+6 weeks |
| Gestational age at delivery | Gestational age at delivery | up to delivery |
| Antepartum complications | including: preeclampsia, gestational diabetes, fetal growth restriction | From enrollment to the day of delivery, up to 42+0 weeks |
| Intrapartum complications | including: fetal distress, dystocia, fever | up to delivery |
| Postpartum complications | including: postpartum hemorrhage, infection, fever | up to 42 days after childbirth |
| Neonatal birthweight | the birthweight of the neonate: unit (kg) | up to delivery |
| Neonatal APGAR score | Neonatal APGAR score at 1 and 5 minutes | up to 5 minutes after delivery |
| Neonatal complications | include neonatal breathing disorders, neonatal infections, neonatal asphyxia, neonatal jaundice, NICU admission for any other causes | up to 7 days after delivery |
| Zhejiang People's Hospital | Hangzhou | Zhejiang | 310014 | China |
|
| Background |
| 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. |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |