Effect of HCQ Combined With LT4 on LBR in Euthyroid Women With URPL and TPO-Ab

Официальное название

The Efficacy of Hydroxychloroquine Combined With Levothyroxine in Euthyroid Women With Thyroid Antibody Positive and Unexplained Recurrent Pregnancy Loss：A Multicenter, Randomized Controlled Study

Обзор

The goal of this clinical trial is to learn if combined treatment of levothyroxine and hydroxychloroquine would improve the live birth of euthyroid women with thyroid peroxidase antibodies and unexplained recurrent pregnancy loss. Researchers will compare combined treatment of levothyroxine and hydroxychloroquine to a treatment of levothyroxine alone to see if combined treatment works to improve live birth of euthyroid participants with thyroid peroxidase antibodies and unexplained recurrent pregnancy loss. Participants will: * Receive combined treatment of levothyroxine and hydroxychloroquine or treatment of levothyroxine alone every day at least 8 weeks before pregnancy, and continue their treatment till the end of pregnancy. * Visit the clinic 4 weeks and 8 weeks after their treatments, and every 12 weeks before they get pregnant for checkups and tests. During their pregnancy, they will visit the clinic before gestation of 12 weeks, and will be followed up with phone call in the second trimester and after parturition.

Подробное описание

Thyroid peroxidase antibodies (TPO-Ab) in euthyroid women are associated with recurrent pregnancy loss. According to 2017 Guidelines of the American Thyroid Association, administration of levothyroxine (LT4) to TPO-Ab-positive euthyroid pregnant women with a prior history of loss may be considered given its potential benefits in comparison with its minimal risk. However, it is a weak recommendation with low-quality evidence. Recently published randomised clinical trials showed that administration of LT4 does not improve pregnancy outcomes of euthyroid thyroid peroxidase antibody positive women with recurrent pregnancy loss. Published data showed TPO-Ab is related to immune imbalance. Hydroxychloroquine is a widely used immune modulator even in fields of autoimmune disorders during pregnancy and lactation. Nevertheless, the effect of hydroxychloroquine combined with LT4 on live birth rate of euthyroid women with TPO-Ab and unexplained recurrent pregnancy loss is unclear. Therefore, we designed a multicenter RCT to verify the study hypothesis that combined treatment of levothyroxine and hydroxychloroquine would improve the live birth rate of euthyroid women with thyroid peroxidase antibodies and unexplained recurrent pregnancy loss.

Вмешательства

• Препарат hydroxychloroquine and levothyroxine
  Hydroxychloroquine sulfate tablets (Fenle, 0.1g) will be given at a total daily dose of 0.2g to 0.4g based on individual weight as described above. During the study, if TSH is higher than 4.0 mIU/L or exceeds the lower limit of the reference range of the center in the first trimester, or TSH level exceeds the normal range of the center during the second or the third trimester, subjects will be instructed to suspend the medication and visit the Department of Endocrinology.
• Препарат Levothyroxine
  Levothyroxine sodium tablets (Euthyrox, 50 μg) will be given 12.5μg \~50 μg daily based on patients' TSH levels and weights as described above. During the study, if TSH is higher than 4.0 mIU/L or exceeds the lower limit of the reference range of the center in the first trimester, or TSH level exceeds the normal range of the center during the second or the third trimester, subjects will be instructed to suspend the medication and visit the Department of Endocrinology.

Первичные конечные точки

• Birth of a living child beyond 28 weeks [Срок оценки: After birth, within 24 months after randomization]

Вторичные конечные точки (12)

• Clinical pregnancy at 5 to 8 weeks [Срок оценки: At 5-8 weeks of pregnancy]
• Miscarriage <28 weeks [Срок оценки: At 28 weeks of pregnancy]
• Gestation at miscarriage, weeks [Срок оценки: After the time of miscarriage, within 24 months after eligibility]
• On-going pregnancy at 12 weeks [Срок оценки: At 12 weeks of pregnancy]
• Gestation at delivery >34 weeks/>37 weeks [Срок оценки: After birth, within 24 months after eligibility]
• Gestation at delivery, weeks [Срок оценки: After birth, within 24 months after eligibility]
• Birth weight, grams [Срок оценки: At birth, within 24 months after eligibility]
• APGAR score at 1 minute/5 minutes [Срок оценки: After birth, within 24 months after eligibility]
• birth defects [Срок оценки: At or short after birth, within 24 months after eligibility]
• Maternal antenatal complications,intrapartum complications,maternal postnatal complications [Срок оценки: up to birth/immediately after delivery]
• Time to pregnancy. [Срок оценки: At 5-8 weeks of pregnancy]
• live birth rate after at least 28 weeks of gestation among pregnant patients [Срок оценки: After birth, within 24 months after randomization]

Критерии участия

Критерии включения

• Women with history of two or more pregnancy loss with the same male partner (including biochemical pregnancies).
• Karyotype analyses show no pathological abnormalities in each individual of the recruited couple.
• Women aged between 20 and 40 years old (including 20 and 40).
• Lupus anticoagulant (LA), anticardiolipin antibody (ACA), and anti-beta2-glycoprotein I antibodies (anti-β2-GP1 Ab) tests are all negative.
• It is confirmed by ultrasound or hysteroscopy that there are no pathological lesions that affect the morphology of the uterine cavity (such as submucosal uterine fibroids, uterine malformations).
• TPO-Ab positive (TPO-Ab > 60 IU/mL using the Siemens kit of electrochemiluminescence method, or TPO-Ab > 34 IU/mL using the Roche kit of chemiluminescence method).
• Biochemically euthyroid. TSH, free triiodothyronine (FT3), and free thyroxine (T4) are all within the reference range of corresponding laboratory testing in each research center.

Критерии исключения

• Rheumatic diseases, such as systemic lupus erythematosus, undifferentiated connective tissue disease, etc.
• Metabolic or endocrine diseases, such as diabetes.
• Abnormal renal function: plasma creatinine level ≥130 μmol/L or abnormal liver function: alanine aminotransferase ≥80U/L or aspartate aminotransferase ≥80U/L.
• Hypertension and malignant tumors.
• Under treatment with glucocorticoids or immunosuppressor, including cyclosporine, azathioprine, prednisone, and methylprednisolone.
• Body Mass Index (BMI) >28kg/m2.
• Past history of hyperthyroidism, hypothyroidism, and thyroid malignant tumors;
• Allergy to 4-aminoquinoline compound, or those with retinal or visual field lesions caused by 4-aminoquinoline compound.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Sun Yat-Sen Memorial Hospital — Гуанчжоу
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University — Гуанчжоу

Идентификаторы

NCT: NCT06652113 · SYSKY-2024-342-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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