Use of Cyclosporin A for the Treatment of Recurrent Miscarriage

Sponsor

Fudan University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02706470

Collaborator

(none)

384

Enrollment

Location

Arms

Duration (Months)

12.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether Cyclosporin A (CsA) - an immunosuppressant drug - in early pregnancy will reduce the risk of miscarriage in women who had a history of unexplained recurrent miscarriages, as compared with that treated with Dydrogesterone-an active comparator. The hypothesis is based on the evidence found in vitro and in vivo experiments that CsA can induce maternal-fetal tolerance so that it may reduce the risk of miscarriage.

Condition or Disease	Intervention/Treatment	Phase
Miscarriage, Recurrent	Drug: Cyclosporin A Drug: Dydrogesterone	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

384 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Controlled Trial of Cyclosporin A for Women With Unexplained Recurrent Miscarriage

Study Start Date :

May 1, 2016

Anticipated Primary Completion Date :

Feb 1, 2018

Anticipated Study Completion Date :

Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cyclosporin A Patients allocated to Cyclosporin A group will receive oral Cyclosporin A in a dose of 50 mg three times a day for 20-30 days in early pregnancy.	Drug: Cyclosporin A Patients will receive oral CsA in a dose of 50mg three times a day for 20-30 days since the occurrence of positive result in human chorionic gonadotropin (HCG) test in urine and 14 consecutive days of elevated basal body temperature. The dosage of CsA will be adjusted according to baseline and peak value of CsA blood concentration. If the baseline blood concentration of CsA is lower than 40ng/ml or the peak blood concentration of CsA is lower than 500ng/ml, the dosage of CsA will be increased to 75 mg three times a day.
Active Comparator: Dydrogesterone Patients allocated to dydrogesterone group will receive oral dydrogesterone in a dose of 10 mg three times a day for 30 days in early pregnancy.	Drug: Dydrogesterone Patients will receive oral dydrogesterone 10 mg three times a day for 30 days since the occurrence of positive result in HCG test in urine and 14 consecutive days of elevated basal body temperature. Other Names: Duphaston

Arm

Intervention/Treatment

Experimental: Cyclosporin A

Patients allocated to Cyclosporin A group will receive oral Cyclosporin A in a dose of 50 mg three times a day for 20-30 days in early pregnancy.

Drug: Cyclosporin A

Patients will receive oral CsA in a dose of 50mg three times a day for 20-30 days since the occurrence of positive result in human chorionic gonadotropin (HCG) test in urine and 14 consecutive days of elevated basal body temperature. The dosage of CsA will be adjusted according to baseline and peak value of CsA blood concentration. If the baseline blood concentration of CsA is lower than 40ng/ml or the peak blood concentration of CsA is lower than 500ng/ml, the dosage of CsA will be increased to 75 mg three times a day.

Active Comparator: Dydrogesterone

Patients allocated to dydrogesterone group will receive oral dydrogesterone in a dose of 10 mg three times a day for 30 days in early pregnancy.

Drug: Dydrogesterone

Patients will receive oral dydrogesterone 10 mg three times a day for 30 days since the occurrence of positive result in HCG test in urine and 14 consecutive days of elevated basal body temperature.

Other Names:

Duphaston

Outcome Measures

Primary Outcome Measures

Live birth rate [Up to 36 months]
The difference in the live birth rates between patients with recurrent miscarriage assigned oral CsA and Dydrogesterone.

Secondary Outcome Measures

The difference in the rate of miscarriage between patients with recurrent miscarriage treated with CsA and Dydrogesterone. [Up to 36 months]
The difference in the rates of miscarriage (pregnancy loss before 20 weeks gestation) between patients assigned oral CsA and Dydrogesterone.
Fetal death [Up to 36 months]
The difference in the rates of fetal death (fetal death after 20 weeks of gestational age) between patients assigned oral CsA and Dydrogesterone.
The difference in the rate of premature delivery between patients treated with CsA and Dydrogesterone. [Up to 36 months]
The difference in the rates of premature delivery (deliveries with gestational age less than 37 weeks) between patients assigned oral CsA and Dydrogesterone.
Congenital malformations [Up to 36 months]
The difference in the rates of congenital malformations between patients assigned oral CsA and Dydrogesterone.
Maternal outcomes: morbidity of infectious disease [Up to 36 months]
The difference of morbidity of infectious disease in pregnancy between two arms.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Both the woman and her husband agree to participate and sign the informed consent form.
Have a history of two or more unexplained recurrent miscarriages.
Spontaneous conception.
Gestational age less than 5 weeks.
Have a normal menstrual cycle (>=23 and <=35 days) and biphasic pattern of basal body temperature before pregnancy.
No significant chromosomal aberrations in the couple.
Semen quality tests show not apparent abnormalities in husband

Exclusion Criteria:

Age below 18 or above 41 years at conception.
Present pregnancy is a result of donor insemination or egg donation.
Significant uterine anomalies detected by ultrasonography, hysterosalpingography, or hysteroscopy.
Contraindications of CsA (e.g. severe infectious diseases, tumor or immunodeficiency) or Dydrogesterone.
Smoking more than 20 daily.