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

Chinese Herbal Medicine (New "Shoutai Wan") and/or Oral Progesterone Intervention Trial for Threatened Miscarriage (CHOP-IT): An International Cooperative Multicenter Randomized Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Threatened Miscarriage
• Intervention / Treatment: Drug: Chinese Herbal Medicine (New "Shoutai Wan") plus Oral Progesterone; Drug: Chinese Herbal Medicine (New "Shoutai Wan") plus Oral Progesterone Placebo; Drug: Chinese Herbal Medicine Placebo (New "Shoutai Wan" placebo) plus Oral Progesterone; Drug: Chinese Herbal Medicine Placebo (New "Shoutai Wan" placebo) plus Oral Progesterone 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.

• Study Type: Interventional
• Enrollment (Actual): 1656
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • The First Affiliated Hospital of Anhui University of Chinese Medicine
  • Guangdong
    • Guangzhou, Guangdong, China
      • Guangdong Provincial Hospital of Chinese Medicine
    • Shenzhen, Guangdong, China
      • Peking University Shenzhen Hospital
  • Heilongjiang
    • Daqing, Heilongjiang, China
      • Da Qing Long Nan Hospital
    • Harbin, Heilongjiang, China
      • First Affiliated Hospital, Heilongjiang University of Chinese Medicine
  • Henan
    • Luoyang, Henan, China
      • Luoyang Hospital of Traditional Chinese Medicine
  • Hunan
    • Changsha, Hunan, China
      • The First Affiliated Hospital of Hunan University of Chinese Medicine
  • Jiangsu
    • Changzhou, Jiangsu, China
      • Changzhou Hospital of Traditional Chinese Medicine
    • Suqian, Jiangsu, China
      • Suqian Maternity Hospital
    • Suqian, Jiangsu, China
      • The People's Hospital of Siyang
    • Xuzhou, Jiangsu, China
      • Xuzhou Central Hospital
    • Xuzhou, Jiangsu, China
      • Xuzhou Maternal and Child Health Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China
      • The Second Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine
    • Nanchang, Jiangxi, China
      • Jiangxi Maternity and Child Health Hospital
  • Liaoning
    • Dalian, Liaoning, China
      • Dalian women and children's medical group
    • Dalian, Liaoning, China
      • Dalian Maternal and Child Health Hospital
    • Shenyang, Liaoning, China
      • The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine
  • Ningxia
    • Yinchuan, Ningxia, China
      • Ningxia Chinese Medicine Research Center
  • Shandong
    • Tai’an, Shandong, China
      • Taian City Central Hospital
  • Shanxi
    • Taiyuan, Shanxi, China
      • Shanxi Traditional Chinese Medical Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Hangzhou Hospital Of Traditional Chinese Medicine
    • Wenzhou, Zhejiang, China
      • Wenzhou TCM Hospital of Zhejiang Chinese Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 37 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.
9. Presence of contributing major medical disorders (regardless of severity). These include poorly controlled diabetes, uncontrolled hypertension, systemic lupus erythematosus (SLE), untreated or active cancer (any cancer in remission or non-melanoma skin cancer is not included in the exclusion criteria), liver disease, renal disease, rheumatoid arthritis, cardiac disease, pulmonary disease other than mild asthma, neurologic disease requiring medical treatment, uncontrolled hypothyroidism, uncontrolled seizure disorder. Untreated vitamin B12 deficiency, severe anemia (hct < 30%), hemophilia, gout, nasal polyps.
10. Known current or recent alcohol abuse or illicit drug use.
11. Known abnormal parental karyotype.
12. Unwilling to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: 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)
Experimental: 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).	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)
Experimental: 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).	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)
Placebo Comparator: 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).	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth	Rate of live birth at or beyond 20 completed weeks' gestation	At or beyond 20 completed weeks' gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy outcome: Ongoing pregnancy	Rate of ongoing pregnancy (beyond 12 weeks' gestation)	Beyond 12 weeks' gestation
Pregnancy outcome: Miscarriage during the first trimester	Rate of miscarriage during the first trimester (at or before 12 weeks' gestation)	During the first trimester (at or before 12 weeks' gestation)
Pregnancy outcome: Miscarriage during second and third trimesters	Rate of miscarriage during second and third trimesters (beyond 12 weeks' gestation until 20 weeks)	During second and third trimesters (beyond 12 weeks' gestation until 20 weeks)
Pregnancy outcome: Termination	Rate of termination at any time during treatment and follow-up period	At any time during treatment (up to 2 months) and follow-up period (up to 1 year)
Pregnancy outcome: Stillbirth	Rate of stillbirth (at or beyond 20 weeks' gestation)	At or beyond 20 weeks' gestation
Pregnancy outcome: Induced abortion	Rate of induced abortion at any time during treatment and follow-up for any reasons	At any time during treatment (up to 2 months) and follow-up period (up to 1 year)
Pregnancy outcome: Full-term birth	Rate of full-term birth (at or beyond 37 weeks' gestation, and before 42 weeks' gestation)	At or beyond 37 weeks' gestation, and before 42 weeks' gestation
Pregnancy outcome: Post-term birth	Rate of post-term birth (at or beyond 42 weeks' gestation)	At or beyond 42 weeks' gestation
Neonatal outcome: Small for gestational age	Rate of small for gestational age when neonatal is born	When neonatal is born
Neonatal outcome: Large for gestational age	Rate of large for gestational age when neonatal is born	When neonatal is born
Neonatal outcome: Congenital malformation	Rate of congenital malformation	At any time during treatment (up to 2 months) and follow-up period (up to 1 year)
Pregnancy outcome: Gestational age at delivery	Gestational age at delivery (weeks and days)	Up to 1 day after delivery
Pregnancy outcome: Preterm birth	Rate of preterm birth (birth beyond 28 week and before 37 completed weeks' gestation (up to and including 36 weeks and 6 days of gestation))	Birth before 37 completed weeks' gestation (up to and including 36 weeks and 6 days of gestation)
Pregnancy outcome: Extreme preterm birth	Rate of extreme preterm birth (birth beyond 20 weeks and before 28 completed weeks' gestation (up to and including 27 weeks and 6 days of gestation))	Birth beyond 20 weeks and before 28 completed weeks' gestation (up to and including 27 weeks and 6 days of gestation)
Neonatal outcome: Birth weight	Birth weight of neonatal (adjusted for gestational age and sex by Chinese standards)	When neonatal is born
Other outcome: Mean score change in TCM Symptom Questionnaire	Mean score change in TCM Symptom Questionnaire from baseline to the end of intervention. The questionnaire covers many dimensions including symptoms (amount of vaginal bleeding, severity of abdominal pain and other general symptoms), emotional factors and so on. The minimum and maximum value are depend on the symptoms of the patient respectively.	From date of randomization until the date of end of treatment, assessed up to 2 months
Other outcome: Mean score change in 12-Item Short-Form Health Survey	Mean score change in 12-Item Short-Form Health Survey from baseline to the end of intervention. The minimum value is 0 and the maximum value is 100, and higher scores mean a better outcome.	From date of randomization until the date of end of treatment, assessed up to 2 months
Other outcome: Mean score change in Self-Rating Anxiety Scale	Mean score change in Self-Rating Anxiety Scale from baseline to the end of intervention. The minimum value is 20 and the maximum value is 80, and lower scores mean a better outcome.	From date of randomization until the date of end of treatment, assessed up to 2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety outcomes: Serious adverse events - Acute kidney injury (AKI)	Rate of acute kidney injury (AKI)	At any time during treatment (up to 2 months) and follow-up period (up to 1 year)
Safety outcomes: Serious adverse events - Drug induced liver injury (DILI)	Rate of drug induced liver injury (DILI)	At any time during treatment (up to 2 months) and follow-up period (up to 1 year)
Safety outcomes: Serious adverse events - Hospitalization	Rate of hospitalization (for threatened abortion in second and third trimester of pregnancy, hyperemesis gravidarum, aggravation-vaginal bleeding, cervical polypectomy, fall injuries and other reasons)	At any time during treatment (up to 2 months) and follow-up period (up to 1 year)
Safety outcomes: Adverse events - Nausea and vomiting	Rate of nausea and vomiting.	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Adverse events - Dizziness	Rate of Dizziness.	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Aadverse events - Fetal and neonatal complications	Rate of fetal and neonatal complications. Fetal complications including distress, and neonatal complications including early infection, NICU admission, pneumonia, hyperbilirubinemia.	From date of randomization until the date of end of pregnancy
Safety outcomes: Adverse events - Fatigue	Rate of Fatigue.	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Adverse events - Anorexia	Rate of Anorexia.	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Adverse events - Constipation	Rate of Constipation.	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Adverse events - Breast distention and pain	Rate of Breast distention and pain	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Adverse events - Upper respiratory tract infection	Rate of Upper respiratory tract infection.	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Adverse events - Abdominal pain	Rate of Abdominal pain	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Adverse events - Somnolence	Rate of Somnolence	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Adverse events - Insomnia	Rate of Insomnia	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Adverse events - Anemia	Rate of Anemia	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Adverse events - Diarrhea	Rate of Diarrhea	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Adverse events - Suspected acute kidney injury (AKI)	Rate of Suspected acute kidney injury (AKI)	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Adverse events - Suspected drug-induced liver injury (DILI).	Rate of Suspected drug-induced liver injury (DILI).	From date of randomization until the date of end of treatment, assessed up to 2 months.
Safety outcomes: Maternal complications - Pregnancy induced hypertension	Rate of Pregnancy induced hypertension	From the date of end of treatment until the date of end of pregnancy, assessed up to 34 weeks.
Safety outcomes: Maternal complications - Pre-eclampsia	Rate of Pre-eclampsia	From the date of end of treatment until the date of end of pregnancy, assessed up to 34 weeks.
Safety outcomes: Maternal complications - Gestational diabetes mellitus	Rate of Gestational diabetes mellitus	From the date of end of treatment until the date of end of pregnancy, assessed up to 34 weeks.
Safety outcomes: Maternal complications - Placenta previa	Rate of Placenta previa	From the date of end of treatment until the date of end of pregnancy, assessed up to 34 weeks.
Safety outcomes: Maternal complications - Pre-labour rupture of membranes	Rate of Pre-labour rupture of membranes	From the date of end of treatment until the date of end of pregnancy, assessed up to 34 weeks.
Safety outcomes: Maternal complications - Postpartum haemorrhage	Rate of Postpartum haemorrhage	From the date of end of treatment until the date of end of pregnancy, assessed up to 34 weeks.
Safety outcomes: Fetal complications - Fatal distress	Rate of Fatal distress	From the date of end of treatment until the date of end of pregnancy, assessed up to 34 weeks.
Safety outcomes: Neonatal complications - Neonatal Early infection	Rate of Neonatal Early infection	From the date of delivery, assessed up to 6 weeks
Safety outcomes: Neonatal complications - Neonatal NICU admission	Rate of Neonatal NICU admission	From the date of delivery, assessed up to 6 weeks
Safety outcomes: Neonatal complications - Neonatal pneumonia	Rate of Neonatal pneumonia	From the date of delivery, assessed up to 6 weeks
Safety outcomes: Neonatal complications - Neonatal hyperbilirubinemia	Rate of Neonatal hyperbilirubinemia	From the date of delivery, assessed up to 6 weeks

Collaborators and Investigators

• Sponsor: Heilongjiang University of Chinese Medicine
• Investigators: Study Chair: Xiao-Ke Wu, Ph.D, First Affiliated Hospital of Heilongjiang Chinese Medicine University

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2017
• Primary Completion (Actual): October 26, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: December 7, 2015
• First Submitted That Met QC Criteria: December 14, 2015
• First Posted (Estimated): December 17, 2015

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 11, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Chinese Herbal Medicine; Live Birth; Micronized Progesterone; Threatened Miscarriage
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Abortion, Threatened; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: CHOP-IT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Subject's privacy is protected undoubtedly at the time of the informed consent signing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No