Chinese Herbal Medicine and Micronized Progesterone for Live Births in Threatened Miscarriage

Threatened Miscarriage Clinical Trial

Official title:

Chinese Herbal Medicine and Micronized Progesterone for Live Births in Threatened Miscarriage: An International Cooperative Multicenter Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02633878
• Other study ID #: CHOP-IT
• Status: Recruiting
• Phase: Phase 2
• Start date: September 1, 2017
• Est. completion date: December 31, 2022

Study information

• Verified date: September 2021
• Source: Heilongjiang University of Chinese Medicine
• Contact: Xiaoke Wu, Ph.D
• Phone: +0086-13796025599
• Email: xiaokewu2002[@]vip.sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 double-bind, randomized and double dummy controlled trial is to determine which of the two oral medications, CHM or micronized progesterone, and will mostly likely result in live birth in women with threatened miscarriage. We will evaluate the efficacy and safety of CHM and micronized progesterone for treating threatened miscarriage in this trial. Our primary outcome of this trial is a live birth. We hypothesize that: 1. treatment with CHM plus micronized progesterone placebo or micronized progesterone plus CHM placebo or CHM plus Micronized progesterone is more likely to result in live birth than the control arm which will be CHM placebo plus micronized progesterone placebo; 2. CHM plus micronized progesterone placebo and micronized progesterone plus CHM placebo will have similar treatment effects.

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. However, the incidence is difficult to determine precisely due to occur 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 not only were found to have increased rate of antepartum haemorrhage, prelabour rupture of the membranes, preterm delivery, and intrauterine growth restriction, but also suffer 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, However, the beneficial effects of hCG still cannot be verified. Progesterone is another most commonly used traditional medication to treat threatened miscarriage, maintaining the endometrial proliferation and preventing spontaneous pregnancy loss. A number of recent studies in women with threatened miscarriage that has shown a reduction in pregnancy loss with progesterone treatment. 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 pregnancy. There is no evidence to identify 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 to treat women with threatened miscarriage due to various factors, and readily accessible, affordable, and safe are needed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1656
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 37 Years

Eligibility

Inclusion criteria

1. Age of women between 20-37 years.

2. Pregnant. The fetus is viable inside the uterine cavity during early pregnancy[1] (5-10 week gestations /35-70 days) as confirmed by positive serum hCG tests and ultrasound, and need to meet either of the following two terms: ? vaginal bleeding with or without abdominal pain, while the cervix is closed by speculum exam; ?Recurrent miscarriage (=2 prior pregnancy losses including biochemical pregnancy and intrauterine pregnancy loss or a pregnancy loss = 6 weeks from LMP).

Exclusion criteria

1. Multiple pregnancies (include twin pregnancies).

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. (4)Non-viable pregnancy. We will define a non-viable pregnancy as: ?an intrauterine pregnancy with a fetal pole without visualized fetal heart motion (>49 days); ?a gestational sac>20 mm in any diameter without a yolk sac; ?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; ?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 and 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. Use of agents that may contribute to bleeding such as aspirin, NSAIDs, etc.

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

10. 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, among others.

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

12. Known abnormal parental karyotype.

13. Unwilling to give informed consent.

14. Unwillingness to be randomized and do not want to take daily medications according to the protocol for up to 12 week gestations (84 days).

Related Conditions & MeSH terms

• Abortion, Spontaneous
• Abortion, Threatened
• Threatened Miscarriage

Intervention

Drug:
• Chinese Herbal Medicine plus Progesterone Capsules
"New Shoutai Pill" Granules plus Micronized Progesterone Capsules
• Chinese Herbal Medicine Placebo plus Progesterone Capsules Placebo
"New Shoutai Pill" Granules Placebo plus Micronized Progesterone Capsules Placebo
• Chinese Herbal Medicine plus Progesterone Capsules Placebo
"New Shoutai Pill" Granules plus Micronized Progesterone Capsules Placebo
• Chinese Herbal Medicine Placebo plus Micronized Progesterone
"New Shoutai Pill" Granules Placebo plus Micronized Progesterone Capsules

Locations

Country	Name	City	State
China	Dalian Maternity Hospital	Dalian	Liaoning
China	Daqing Longnan Hospital	Daqing	Heilongjiang
China	Hangzhou hospital of Chinese medicine	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Jiangxi University of Chinese Medicine	Nanchang	Jiangxi
China	Shenzhen Hospital of Beijing University	Shenzhen	Guangdong
China	Shanxi Province Hospital of Chinese medicine	Taiyuan	Shanxi
China	Wenzhou Hospital of Chinese Medicine	Wenzhou	Zhejiang
China	Xuzhou Central Hospital	Xuzhou	Jiangsu
China	Xuzhou Maternal and Child Health Hospital	Xuzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Heilongjiang University of Chinese Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Live birth rate	Cumulative live birth rate	>20 weeks of gestation
Secondary	Ongoing pregnancy rate	Cumulative Ongoing pregnancy rate	Beyond gestation 12 weeks
Secondary	Ongoing pregnancy rate	Cumulative Ongoing pregnancy rate	Beyond gestation 20 weeks
Secondary	Ongoing pregnancy rate	Cumulative Ongoing pregnancy rate	Beyond gestation 32 weeks
Secondary	Live birth rate	Cumulative live birth rate	>37 weeks of gestation
Secondary	Premature live birth rate	Cumulative Premature live birth rate	>24, but< weeks of gestation
Secondary	Anti-ß2 glycoprotein-I antibodies	The number or percentage of Anti-ß2 glycoprotein-I antibodies positive patients	Baseline and end of treatment
Secondary	Lupus anticoagulant	The number or percentage of Lupus anticoagulant positive patients	Baseline and end of treatment
Secondary	Anti-cardiolipin antibody	The number or percentage of Anti-cardiolipin antibody positive patients	Baseline and end of treatment
Secondary	Pregnancy loss rate	The number or percentage of patients who have a pregnancy loss	Before 20 weeks of gestation
Secondary	Pregnancy loss rate	The number or percentage of patients who have a pregnancy loss	After 20 weeks of gestation
Secondary	Serum Progesterone	Value (Units: ng/ml)	Baseline, each visit and end of the treatment
Secondary	Zung Self-Rating Anxiety Scale	Change in scores	Baseline and end of treatment
Secondary	SF-12 Health Survey	Change in scores	Baseline and end of treatment
Secondary	Adverse event and/or serious adverse event	Pregnancy-induced hypertension, diabetes and antepartum haemorrhage, preterm birth, postdate delivery, preeclampsia and so on	During treatment, the second and third trimester, postpartum, fetus and newborn