Chinese Herbal Medicine (New "Shoutai Wan") and/or Oral Progesterone Intervention Trial for Threatened Miscarriage

NCT ID: NCT02633878

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1656 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-20
• Study Completion Date: 2025-12-31

Brief Summary

Threatened miscarriage is manifested by vaginal bleeding, with or without abdominal pain, while the cervix is closed and the fetus is viable and inside the uterine cavity. Threatened miscarriage is a common complication of pregnancy occurring in 20% of all clinically recognized pregnancies and about half of these will eventually result in pregnancy loss. The goal of this two by two factorial, placebo controlled randomized trial is to determine that two oral medications and their combination, will mostly likely result in live birth in women with threatened miscarriage. We will evaluate the efficacy and safety of Chinese herbal medicine (New "Shoutai Wan", NSTW) and/or oral micronized progesterone (OP) for treating threatened miscarriage in this trial. Our primary outcome of this trial is live birth. We hypothesize that: 1. treatment with NSTW plus OP or OP placebo is more likely to result in live birth than NSTW placebo plus OP or placebo; 2. treatment with OP plus NSTW or NSTW placebo is more likely to result in live birth than OP placebo plus NSTW or NSTW placebo; 3. treatment with combination of NSTW and OP is more likely to result in live birth than combination of NSTW placebo and OP placebo.

Detailed Description

The causes of spontaneous miscarriage are diverse and comprise chromosomal, genetic, anatomical, immunological, hormonal, infectious and psychological factors, the other factors contribute to an increased risk include advancing paternal and maternal age and mothers with systemic diseases, such as diabetes or thyroid dysfunction. The incidence is difficult to determine precisely because it occurs very early during a pregnancy and almost 30% of early pregnancy may go unrecognized; the pathogenesis of pregnancy loss in this condition is still remains obscure. Compared with healthy women, the women with threatened miscarriage were found not only to have increased rate of antepartum haemorrhage, prelabour rupture of the membranes, preterm delivery, and intrauterine growth restriction, but also suffer from significant psychological impairment including considerable anxiety and stress, depression, sleep disturbances, anger, and marital disturbances.

To date, therapies have limited effectiveness in treating threatened miscarriage and are empirical. Bed rest does not prevent pregnancy loss. Acetaminophen may have some effects on relieving pain only. The most commonly used prescription medication was human chorionic gonadotropin (hCG), maintaining the luteotrophic effects to support continued secretion of estrogen and progesterone, but it's beneficial effects still cannot be verified. Progesterone is another most commonly used standard medication, maintaining the endometrial proliferation and preventing poor decidualization. A number of recent studies in women with threatened miscarriage shown a reduction in pregnancy loss with progesterone treatment. But progestogens are a group of hormones, including both the natural female sex hormone progesterone and the synthetic forms. Micronized progesterone is a kind of progesterone; it is structurally and pharmacologically very similar to natural progesterone and has good oral bioavailability. It is especially suitable for women with threatened miscarriage as it does not have androgenic or oestrogenic effects on the foetus. A recent review of maternal use of micronized progesterone during pregnancy also found no evidence for an increased risk of congenital malformations. However it may only be suitable to treat women with threatened miscarriage who have low progesterone levels due to corpus luteum deficiency at the first trimester of pregnancy. There is no evidence to show the beneficial effects of progesterone to treat threatened miscarriage due to others factors. At the same time, progesterone treatment is also expensive. New or adjuvant treatments that are suitable, readily accessible, affordable, and safe are needed to treat women with threatened miscarriage.

Conditions

Threatened Miscarriage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

NSTW + OP

NSTW one pack twice daily until 12 weeks of gestations (max 84 days); OP 100 mg thrice daily until 12 weeks of gestations (max 84 days).

Group Type: EXPERIMENTAL

Chinese Herbal Medicine (New "Shoutai Wan") plus Oral Progesterone

Intervention Type: DRUG

Chinese Herbal Medicine (New "Shoutai Wan", one pack twice daily) + Oral Progesterone (100 mg thrice daily)

NSTW + OP placebo

NSTW one pack twice daily until 12 weeks of gestations (max 84 days); OP Placebo 100 mg thrice daily until 12 weeks of gestations (max 84 days).

Group Type: EXPERIMENTAL

Chinese Herbal Medicine (New "Shoutai Wan") plus Oral Progesterone Placebo

Intervention Type: DRUG

Chinese Herbal Medicine (New "Shoutai Wan", one pack twice daily) + Oral Progesterone Placebo (100 mg thrice daily)

NSTW Placebo + OP

NSTW Placebo one pack twice daily until 12 weeks of gestations (max 84 days); OP 100 mg thrice daily until 12 weeks of gestations (max 84 days).

Group Type: EXPERIMENTAL

Chinese Herbal Medicine Placebo (New "Shoutai Wan" placebo) plus Oral Progesterone

Intervention Type: DRUG

Chinese Herbal Medicine Placebo (New "Shoutai Wan" placebo, one pack twice daily) + Oral Progesterone (100 mg thrice daily)

NSTW Placebo + OP Placebo

NSTW Placebo one pack twice daily until 12 weeks of gestations (max 84 days); OP Placebo 100 mg thrice daily until 12 weeks of gestations (max 84 days).

Group Type: PLACEBO_COMPARATOR

Chinese Herbal Medicine Placebo (New "Shoutai Wan" placebo) plus Oral Progesterone Placebo

Intervention Type: DRUG

Chinese Herbal Medicine Placebo (New "Shoutai Wan" placebo, one pack twice daily) + Oral Progesterone Placebo (100 mg thrice daily)

Interventions

Chinese Herbal Medicine (New "Shoutai Wan") plus Oral Progesterone

Chinese Herbal Medicine (New "Shoutai Wan", one pack twice daily) + Oral Progesterone (100 mg thrice daily)

Intervention Type: DRUG

Chinese Herbal Medicine (New "Shoutai Wan") plus Oral Progesterone Placebo

Chinese Herbal Medicine (New "Shoutai Wan", one pack twice daily) + Oral Progesterone Placebo (100 mg thrice daily)

Intervention Type: DRUG

Chinese Herbal Medicine Placebo (New "Shoutai Wan" placebo) plus Oral Progesterone

Chinese Herbal Medicine Placebo (New "Shoutai Wan" placebo, one pack twice daily) + Oral Progesterone (100 mg thrice daily)

Intervention Type: DRUG

Chinese Herbal Medicine Placebo (New "Shoutai Wan" placebo) plus Oral Progesterone Placebo

Chinese Herbal Medicine Placebo (New "Shoutai Wan" placebo, one pack twice daily) + Oral Progesterone Placebo (100 mg thrice daily)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age of women between 20-37 years.

2. Pregnant. The fetus is viable inside the uterine cavity during early pregnancy (5-10 week gestations) by ultrasound and/or serum hCG changes.

3. Bleeding symptoms: vaginal bleeding with or without abdominal pain, while the cervix is closed in during speculum examination.

Exclusion Criteria

1. Multiple pregnancies (more than one gestational sac or fetal pole in ultrasonography).

2. Ectopic pregnancy. We will define an ectopic pregnancy as any suspected adnexal mass or large amounts of free fluid in the pelvis without an accompanying intrauterine pregnancy.

3. Pregnancies of Unknown Location (PUL). This will include pregnancies with an hCG level >2500mIU/mL without visualization of an intrauterine or extrauterine (i.e. ectopic) pregnancies.

4. Non-viable pregnancy. We will define a non-viable pregnancy as: (1) an intrauterine pregnancy with a fetal pole without visualized fetal heart motion (>49 days); (2) a gestational sac>20 mm in any diameter without a yolk sac; (3) absence of a normal gestational sac at 5 weeks of pregnancy, absence of a yolk sac at 5.5-6 weeks of pregnancy, or absence of cardiac activity at 7 weeks of pregnancy by ultrasound; (4) falling serum hCG values on serial visits or between baseline and randomization visit, or serial serum hCG levels which show a plateau (2-day increase ≤ 10%).

5. Intrauterine abnormalities or submucosal fibroids distorting uterine cavity (as assessed by ultrasound).

6. Bleeding attributed to a vulvar, vaginal, or cervical source unrelated to the pregnancy.

7. For this threatened miscarriage, use of the same or similar Chinese medicine and/or progesterone more than one week.

8. History of a congenital or acquired bleeding diathesis, i.e. Hemophilia, Von Willebrands's Disease, use of anti-coagulants, etc.

10. Known current or recent alcohol abuse or illicit drug use.

11. Known abnormal parental karyotype.

12. Unwilling to give informed consent.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 37 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Heilongjiang University of Chinese Medicine

OTHER

Sponsor Role: lead

Responsible Party

Xiaoke Wu

Director of Obstetrics and Gynecology Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiao-Ke Wu, Ph.D

Role: STUDY_CHAIR

First Affiliated Hospital of Heilongjiang Chinese Medicine University

Locations

The First Affiliated Hospital of Anhui University of Chinese Medicine

Hefei, Anhui, China

Guangdong Provincial Hospital of Chinese Medicine

Guangzhou, Guangdong, China

Peking University Shenzhen Hospital

Shenzhen, Guangdong, China

Da Qing Long Nan Hospital

Daqing, Heilongjiang, China

First Affiliated Hospital, Heilongjiang University of Chinese Medicine

Harbin, Heilongjiang, China

Luoyang Hospital of Traditional Chinese Medicine

Luoyang, Henan, China

The First Affiliated Hospital of Hunan University of Chinese Medicine

Changsha, Hunan, China

Changzhou Hospital of Traditional Chinese Medicine

Changzhou, Jiangsu, China

Suqian Maternity Hospital

Suqian, Jiangsu, China

The People's Hospital of Siyang

Suqian, Jiangsu, China

Xuzhou Central Hospital

Xuzhou, Jiangsu, China

Xuzhou Maternal and Child Health Hospital

Xuzhou, Jiangsu, China

Jiangxi Maternity and Child Health Hospital

Nanchang, Jiangxi, China

The Second Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine

Nanchang, Jiangxi, China

Dalian Maternal and Child Health Hospital

Dalian, Liaoning, China

Dalian women and children's medical group

Dalian, Liaoning, China

The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine

Shenyang, Liaoning, China

Ningxia Chinese Medicine Research Center

Yinchuan, Ningxia, China

Taian City Central Hospital

Tai’an, Shandong, China

Shanxi Traditional Chinese Medical Hospital

Taiyuan, Shanxi, China

Hangzhou Hospital of Traditional Chinese Medicine

Hangzhou, Zhejiang, China

Wenzhou TCM Hospital of Zhejiang Chinese Medical University

Wenzhou, Zhejiang, China

Countries

China

Other Identifiers

CHOP-IT

Identifier Type: -

Identifier Source: org_study_id