Hydroxychloroquine plus levothyroxine for improving live birth in euthyroid women with recurrent pregnancy loss and TPO antibodies
The Efficacy of Hydroxychloroquine Combined With Levothyroxine in Euthyroid Women With Thyroid Antibody Positive and Unexplained Recurrent Pregnancy Loss：A Multicenter, Randomized Controlled Study
This trial will test whether adding hydroxychloroquine to levothyroxine increases the chance of a live birth for euthyroid women who have thyroid peroxidase antibodies and a history of recurrent pregnancy loss.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 796 (estimated) |
| Ages | 20 Years to 40 Years |
| Sex | Female |
| Sponsor | Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Academic / other |
| Drugs / interventions | prednisone |
| Locations | 2 sites (Guangzhou, Guangdong and 1 other locations) |
| Trial ID | NCT06652113 on ClinicalTrials.gov |
What this trial studies
This is a multicenter randomized trial comparing combined hydroxychloroquine (HCQ) plus levothyroxine (LT4) versus LT4 alone in euthyroid women who are positive for thyroid peroxidase antibodies and have unexplained recurrent pregnancy loss. Participants begin daily treatment at least eight weeks before attempting pregnancy and continue the assigned treatment through the end of pregnancy. Study visits occur at 4 and 8 weeks after treatment start, every 12 weeks before pregnancy, and during early pregnancy with additional phone follow-up; the primary outcome is live birth rate. The trial enrolls women aged 20–40 with negative antiphospholipid tests, normal couple karyotypes, and no uterine structural pathology.
Who should consider this trial
Good fit: Women aged 20–40 with two or more prior pregnancy losses, confirmed euthyroid status, positive TPO antibodies, normal partner and patient karyotypes, negative antiphospholipid antibody tests, and no uterine structural lesions are the intended participants.
Not a fit: Women who are not TPO-Ab positive, have abnormal thyroid function, positive antiphospholipid antibodies, significant uterine pathology, chromosomal abnormalities, or cannot attend the Guangzhou clinic visits are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, the combination could raise live birth rates for euthyroid women with TPO antibodies and unexplained recurrent pregnancy loss.
How similar studies have performed: Previous randomized trials found levothyroxine alone did not improve outcomes in this population, hydroxychloroquine is used safely as an immunomodulator in pregnancy for other autoimmune conditions, but combining HCQ with LT4 for this indication is novel and unproven.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Guangzhou, Guangdong and 1 other locations
- Sun Yat-Sen Memorial Hospital — Guangzhou, Guangdong, China (Recruiting)
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University — Guangzhou, Guangdong, China (Not_yet_recruiting)
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.