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

Sun Yat-sen University

Status: Not yet enrolling

Conditions: Recurrent Pregnancy Loss; Euthyroid With Thyroid Antibodies

Treatments: Drug: Levothyroxine; Drug: hydroxychloroquine and levothyroxine

Study type: Interventional

Funder types: Other

Identifiers

NCT06652113

SYSKY-2024-342-01

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 796 estimated patients

Sex: Female

Ages: 20 to 40 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Women with history of two or more pregnancy loss with the same male partner (including biochemical pregnancies).
2. Karyotype analyses show no pathological abnormalities in each individual of the recruited couple.
3. Women aged between 20 and 40 years old (including 20 and 40).
4. Lupus anticoagulant (LA), anticardiolipin antibody (ACA), and anti-beta2-glycoprotein I antibodies (anti-β2-GP1 Ab) tests are all negative.
5. 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).
6. 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).
7. Biochemically euthyroid. TSH, free triiodothyronine (FT3), and free thyroxine (T4) are all within the reference range of corresponding laboratory testing in each research center.

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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796 participants in 2 patient groups

hydroxychloroquine and levothyroxine group

Experimental group

Description:

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%.

Treatment:

Drug: hydroxychloroquine and levothyroxine

levothyroxine group

Other group

Description:

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%.

Treatment:

Drug: Levothyroxine