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

Last updated: September 17, 2025
Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Overall Status: Active - Recruiting

Phase

N/A

Condition

Recurrent Pregnancy Loss

Treatment

hydroxychloroquine and levothyroxine

Levothyroxine

Clinical Study ID

NCT06652113
SYSKY-2024-342-01
  • Ages 20-40
  • Female

Study Summary

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.

Eligibility Criteria

Inclusion

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 therecruited couple.

  3. Women aged between 20 and 40 years old (including 20 and 40).

  4. Lupus anticoagulant (LA), anticardiolipin antibody (ACA), andanti-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 lesionsthat affect the morphology of the uterine cavity (such as submucosal uterinefibroids, uterine malformations).

  6. TPO-Ab positive (TPO-Ab > 60 IU/mL using the Siemens kit of electrochemiluminescencemethod, 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 eachresearch center.

Exclusion

Exclusion criteria:

  1. Rheumatic diseases, such as systemic lupus erythematosus, undifferentiatedconnective tissue disease, etc.

  2. Metabolic or endocrine diseases, such as diabetes.

  3. Abnormal renal function: plasma creatinine level ≥130 μmol/L or abnormal liverfunction: 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 lesionscaused by 4-aminoquinoline compound.

Study Design

Total Participants: 796
Treatment Group(s): 2
Primary Treatment: hydroxychloroquine and levothyroxine
Phase:
Study Start date:
November 15, 2024
Estimated Completion Date:
March 31, 2037

Study 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.

Connect with a study center

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

    Guangzhou, Guangdong 510120
    China

    Site Not Available

  • Sun Yat-Sen Memorial Hospital

    Guangzhou 1809858, Guangdong 1809935 510000
    China

    Active - Recruiting

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

    Guangzhou 1809858, Guangdong 1809935 510120
    China

    Site Not Available

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