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

NCT06652113 | Recruiting DMC

• 1 other identifier: SYSKY-2024-342-01
• Study Type: interventional
• Target: 796
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Recurrent Pregnancy Loss; Euthyroid With Thyroid Antibodies

Keywords

live birth; euthyroid; thyroid peroxidase antibody; recurrent pregnancy loss

Outcome Measures

Primary Outcomes (1)

• Birth of a living child beyond 28 weeks

  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.

  After birth, within 24 months after randomization

Secondary Outcomes (12)

• 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

Study Arms (2)

hydroxychloroquine and levothyroxine group

EXPERIMENTAL

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%.

Drug: hydroxychloroquine and levothyroxine

levothyroxine group

OTHER

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%.

Drug: Levothyroxine

Interventions

hydroxychloroquine and levothyroxine DRUG

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.

hydroxychloroquine and levothyroxine group

Levothyroxine DRUG

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.

levothyroxine group

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (2)

Sun Yat-Sen Memorial Hospital

Guangzhou, Guangdong, 510000, China

RECRUITING

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

Guangzhou, Guangdong, 510120, China

NOT YET RECRUITING

MeSH Terms

Interventions

Hydroxychloroquine; Thyroxine

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open-labeled multicenter randomized clinical trial

Study Record Dates

• First Submitted: June 25, 2024
• First Posted: October 22, 2024
• Study Start: November 15, 2024
• Primary Completion (Estimated): March 1, 2035
• Study Completion (Estimated): March 1, 2037
• Last Updated: September 23, 2025

Record last verified: 2025-09

Locations

CN (2)