The Efficacy of Hydroxychloroquine Combined With Levothyroxine in Euthyroid Women With Thyroid Antibody Positive and Unexplained Recurrent Pregnancy Loss：A Multicenter, Randomized Controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 796
- 试验地点
- 2
- 主要终点
- Birth of a living child beyond 28 weeks
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
hydroxychloroquine and levothyroxine group
Corresponding oral treatment will be initiated after randomization and preconceptually, and continue to the end of pregnancy or until 60 weeks post-randomisation if pregnancy does not occur. Patients in the experimental group will be given a combined oral treatment of hydroxychloroquine (HCQ) 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: patients weighing ≤46kg take HCQ tablets 0.2g/d, patients weighing >46kg and <62kg take HCQ tablets 0.3g/d, patients weighing ≥62kg take HCQ tablets 0.4g/d. Levothyroxine sodium tablets (Euthyrox, 50 μg) will be given 12.5μg ~50 μg daily based on patients' TSH levels and weights: TSH ≥ 2.5 mIU/L, the dosage is 50 μg/d; TSH < 2.5 mIU/L, the dosage is 25 μg/d; when the patient's weight is less than 50kg, the dosage is reduced by 50%.
干预措施: hydroxychloroquine and levothyroxine (Drug)
levothyroxine group
Corresponding oral treatment will be initiated after randomization and preconceptually, and continued to the end of any pregnancy or until 60 weeks post-randomisation if pregnancy does not occur. Patients assigned in the control group will be given levothyroxine daily. Levothyroxine sodium tablets (Euthyrox, 50 μg) will be given 12.5μg ~50 μg daily based on patients' TSH levels and weights: TSH ≥ 2.5 mIU/L, the dosage is 50 μg/d; TSH < 2.5 mIU/L, the dosage is 25 μg/d; when the patient's weight is less than 50kg, the dosage is reduced by 50%.
干预措施: Levothyroxine (Drug)
结局指标
主要结局
Birth of a living child beyond 28 weeks
时间窗: After birth, within 24 months after randomization
The primary outcome is the proportion of women with a live birth at or beyond 28 completed weeks. This proportion will be calculated with the denominator totalling all women randomised, and the numerator (i.e., treatment successes) totalling women who conceive within 60 weeks of randomisation and go on to give live birth at or beyond 28 weeks gestation.
次要结局
- APGAR score at 1 minute/5 minutes(After birth, within 24 months after eligibility)
- birth defects(At or short after birth, within 24 months after eligibility)
- Clinical pregnancy at 5 to 8 weeks(At 5-8 weeks of pregnancy)
- Miscarriage <28 weeks(At 28 weeks of pregnancy)
- Gestation at miscarriage, weeks(After the time of miscarriage, within 24 months after eligibility)
- On-going pregnancy at 12 weeks(At 12 weeks of pregnancy)
- Gestation at delivery >34 weeks/>37 weeks(After birth, within 24 months after eligibility)
- Gestation at delivery, weeks(After birth, within 24 months after eligibility)
- Birth weight, grams(At birth, within 24 months after eligibility)
- Maternal antenatal complications,intrapartum complications,maternal postnatal complications(up to birth/immediately after delivery)
- Time to pregnancy.(At 5-8 weeks of pregnancy)
- live birth rate after at least 28 weeks of gestation among pregnant patients(After birth, within 24 months after randomization)