Chinese Herbal Medicine and/or Oral Progesterone Intervention Trial for Threatened Miscarriage

Last updated: October 28, 2024
Sponsor: Heilongjiang University of Chinese Medicine
Overall Status: Active - Recruiting

Phase

3

Condition

N/A

Treatment

Chinese Herbal Medicine plus Oral Micronized Progesterone Placebo

Chinese Herbal Medicine Placebo plus Oral Micronized Progesterone Placebo

Chinese Herbal Medicine Placebo plus Oral Micronized Progesterone

Clinical Study ID

NCT02633878
CHOP-IT
  • Ages 20-37
  • Female

Study 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 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.

Eligibility Criteria

Inclusion

Inclusion criteria:

  1. Age of women between 20-37 years.

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

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

Exclusion

Exclusion criteria:

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

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

  3. Pregnancies of Unknown Location (PUL). This will include pregnancies with an hCGlevel >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: ①an intrauterinepregnancy with a fetal pole without visualized fetal heart motion (>49 days); ②agestational sac>20 mm in any diameter without a yolk sac; ③absence of a normalgestational sac at 5 weeks of pregnancy, absence of a yolk sac at 5.5-6 weeks ofpregnancy, or absence of cardiac activity at 7 weeks of pregnancy by ultrasound; ④falling serum hCG values on serial visits or between baseline and randomizationvisit, or serial serum hCG levels which show a plateau (2-day increase ≤ 10%).

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

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

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

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

  9. Presence of contributing major medical disorders (regardless of severity). Theseinclude poorly controlled diabetes, uncontrolled hypertension, systemic lupuserythematosus (SLE), untreated or active cancer (any cancer in remission ornon-melanoma skin cancer is not included in the exclusion criteria), liver disease,renal disease, rheumatoid arthritis, cardiac disease, pulmonary disease other thanmild asthma, neurologic disease requiring medical treatment, uncontrolledhypothyroidism, 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.

  13. Unwillingness to be randomized.

Study Design

Total Participants: 1656
Treatment Group(s): 4
Primary Treatment: Chinese Herbal Medicine plus Oral Micronized Progesterone Placebo
Phase: 3
Study Start date:
October 20, 2017
Estimated Completion Date:
August 31, 2025

Study 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.

Connect with a study center

  • First Affiliated Hospital of Anhui University of Chinese Medicine

    Hefei, Anhui
    China

    Completed

  • Guangdong Provincial Hospital of Chinese Medicine

    Guangzhou, Guangdong
    China

    Completed

  • Shenzhen Hospital of Beijing University

    Shenzhen, Guangdong
    China

    Completed

  • Daqing Longnan Hospital

    Daqing, Heilongjiang
    China

    Completed

  • First Affiliated Hospital, Heilongjiang University of Chinese Medicine

    Harbin, Heilongjiang
    China

    Completed

  • The First Affiliated Hospital of Heilongjiang University of Chinese Medicine

    Harbin, Heilongjiang 150028
    China

    Site Not Available

  • Luoyang Hospital of Traditional Chinese Medicinel

    Luoyang, Henan
    China

    Active - Recruiting

  • First Affiliated Hospital, Hunan University of Chinese Medicine

    Changsha, Hunan
    China

    Completed

  • Changzhou Hospital of Chinese Medicine

    Changzhou, Jiangsu
    China

    Completed

  • Siyang People's Hospital

    Suqian, Jiangsu
    China

    Completed

  • Suqian Obstetrics and Gynecology Hospital

    Suqian, Jiangsu
    China

    Completed

  • Xuzhou Central Hospital

    Xuzhou, Jiangsu
    China

    Active - Recruiting

  • Xuzhou Central Hospitall

    Xuzhou, Jiangsu
    China

    Completed

  • Xuzhou Maternal and Child Health Hospital

    Xuzhou, Jiangsu
    China

    Completed

  • Jiangxi Maternal and Child Health Hospital

    Nanchang, Jiangxi
    China

    Active - Recruiting

  • The Second Affiliated Hospital of Jiangxi University of Chinese Medicine

    Nanchang, Jiangxi
    China

    Completed

  • Dalian Maternal Hospital

    Dalian, Liaoning
    China

    Completed

  • Dalian Maternity Hospital

    Dalian, Liaoning
    China

    Active - Recruiting

  • Dalian Municipal Women And Children's Medical Center

    Dalian, Liaoning
    China

    Completed

  • Affiliated Hospital, Liaoning University of Chinese Medicine

    Shenyang, Liaoning
    China

    Completed

  • Ningxia Hui Autonomous Region Hospital of traditional Chinese Medicine

    Yinchuan, Ningxia Hui Autonomous Region
    China

    Completed

  • Taian City Central Hospital

    Tai'an, Shandong
    China

    Completed

  • Shanxi Province Hospital of Chinese Medicine

    Taiyuan, Shanxi
    China

    Completed

  • Hangzhou Hospital of Chinese Medical

    Hangzhou, Zhejiang
    China

    Completed

  • Hangzhou hospital of Chinese medicine

    Hangzhou, Zhejiang
    China

    Active - Recruiting

  • Wenzhou Hospital of Chinese Medicine

    Wenzhou, Zhejiang
    China

    Completed

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