Chinese Herbal Medicine (New "Shoutai Wan") and/or Oral Progesterone Intervention Trial for Threatened Miscarriage (CHOP-IT): An International Cooperative Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,656
- 试验地点
- 22
- 主要终点
- Live birth
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 37 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age of women between 20-37 years.
- •Pregnant. The fetus is viable inside the uterine cavity during early pregnancy (5-10 week gestations) by ultrasound and/or serum hCG changes.
- •Bleeding symptoms: vaginal bleeding with or without abdominal pain, while the cervix is closed in during speculum examination.
排除标准
- •Multiple pregnancies (more than one gestational sac or fetal pole in ultrasonography).
- •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.
- •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.
- •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%).
- •Intrauterine abnormalities or submucosal fibroids distorting uterine cavity (as assessed by ultrasound).
- •Bleeding attributed to a vulvar, vaginal, or cervical source unrelated to the pregnancy.
- •For this threatened miscarriage, use of the same or similar Chinese medicine and/or progesterone more than one week.
- •History of a congenital or acquired bleeding diathesis, i.e. Hemophilia, Von Willebrands's Disease, use of anti-coagulants, etc.
- •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.
- •Known current or recent alcohol abuse or illicit drug use.
- •Known abnormal parental karyotype.
- •Unwilling to give informed consent.
研究组 & 干预措施
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).
干预措施: Chinese Herbal Medicine (New "Shoutai Wan") plus Oral Progesterone (Drug)
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).
干预措施: Chinese Herbal Medicine (New "Shoutai Wan") plus Oral Progesterone Placebo (Drug)
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).
干预措施: Chinese Herbal Medicine Placebo (New "Shoutai Wan" placebo) plus Oral Progesterone (Drug)
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).
干预措施: Chinese Herbal Medicine Placebo (New "Shoutai Wan" placebo) plus Oral Progesterone Placebo (Drug)
结局指标
主要结局
Live birth
时间窗: At or beyond 20 completed weeks' gestation
Rate of live birth at or beyond 20 completed weeks' gestation
次要结局
- Pregnancy outcome: Ongoing pregnancy(Beyond 12 weeks' gestation)
- Pregnancy outcome: Miscarriage during the first trimester(During the first trimester (at or before 12 weeks' gestation))
- Pregnancy outcome: Miscarriage during second and third trimesters(During second and third trimesters (beyond 12 weeks' gestation until 20 weeks))
- Pregnancy outcome: Termination(At any time during treatment (up to 2 months) and follow-up period (up to 1 year))
- Pregnancy outcome: Stillbirth(At or beyond 20 weeks' gestation)
- Pregnancy outcome: Induced abortion(At any time during treatment (up to 2 months) and follow-up period (up to 1 year))
- Pregnancy outcome: Post-term birth(At or beyond 42 weeks' gestation)
- Pregnancy outcome: Gestational age at delivery(Up to 1 day after delivery)
- Pregnancy outcome: Preterm birth(Birth before 37 completed weeks' gestation (up to and including 36 weeks and 6 days of gestation))
- Pregnancy outcome: Extreme preterm birth(Birth beyond 20 weeks and before 28 completed weeks' gestation (up to and including 27 weeks and 6 days of gestation))
- Pregnancy outcome: Full-term birth(At or beyond 37 weeks' gestation, and before 42 weeks' gestation)
- Neonatal outcome: Birth weight(When neonatal is born)
- Neonatal outcome: Small for gestational age(When neonatal is born)
- Neonatal outcome: Large for gestational age(When neonatal is born)
- Neonatal outcome: Congenital malformation(At any time during treatment (up to 2 months) and follow-up period (up to 1 year))
- Other outcome: Mean score change in TCM Symptom Questionnaire(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(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(From date of randomization until the date of end of treatment, assessed up to 2 months)
研究者
Xiaoke Wu
Director of Obstetrics and Gynecology Department
Heilongjiang University of Chinese Medicine