Traditional Chinese Medicine Sequential Treatment for Endometriosis Associated Infertility

Infertility Clinical Trial

Official title:

Activating Blood, Dredging Liver and Nourishing Kidney Sequential Treatment for Endometriosis Associated Infertility - a Randomized Double-blind Placebo Controlled Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02676713
• Other study ID #: GAMHospital
• Secondary ID: 2014BAI10B08
• Status: Recruiting
• Phase: Phase 2
• First received: August 16, 2015
• Last updated: February 17, 2016
• Start date: December 2014
• Est. completion date: December 2017

Study information

• Verified date: February 2016
• Source: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
• Contact: Yi Tang, Master
• Phone: +86 13260185007
• Email: yier1990[@]126.com
• Is FDA regulated: No
• Health authority: China: Ministry of Science and Technology
• Study type: Interventional

Clinical Trial Summary

Endometriosis is a common, chronic disease. 30% to 50% of women with endometriosis are infertile. There is moderate quality evidence that laparoscopic surgery to treat mild and moderate endometriosis increases live birth or ongoing pregnancy rates. There was no evidence of benefit for post-surgical hormonal suppression of endometriosis compared to surgery alone for the outcomes of pregnancy rates. Past studies have confirmed that Chinese herbal medicine can inhibit post-surgical endometriosis recurrence, increase pregnancy rate.This study evaluates the efficacy and safety of Traditional Chinese Medicine Sequential Treatment of endometriosis-associated infertility. The study objective is to confirm that clinical pregnancy rate of patients with endometriosis-associated infertility post-conservative surgery accepting Chinese medicine activating blood, dredging liver and nourishing kidney sequential treatment is higher than expectant treatment.

Description:

This study is a randomized, double-blind, placebo-controlled, multicenter, prospective clinical study, conducted in China (six research centers).

204 cases of patients with endometriosis-associated infertility confined with Syndrome of qi stagnation blood stasis pattern in TCM after conservative surgery will be recruited. Patients will be randomly divided into two groups: experimental group (TCM Sequential Treatment) and control group (placebo). All the patients are treated for six menstrual cycles, taking pre-ovulation decoction before ovulation and post-ovulation decoction after ovulation. Pre-ovulation decoction of experimental group is HuoXueXiaoYi decoction, and post-ovulation decoction is BuShenZhuYun decoction. The drug of control group is placebo.

Each menstrual cycle, patient is monitored of antral follicle count (AFC), ovulation, endometrial thickness, and endometrial blood flow by ultrasonography, and need fill TCM syndrome rating scale, pictorial blood loss assessment chart (PBAC), and the visual analogue scale(VAS).The 1st, 3rd, 6th menstrual cycle after surgery, the level of serum female hormone (FSH, LH, E2) are detected in menstrual period of 2 to 5 days, and female hormone (E2, P) in the middle of the corpus luteum 6-9 days.

Patient must be security check (blood routine, urine routine, liver and kidney function, electrocardiogram) before and after drug treatment. Such as patients find pregnancy during medication, adopt the security check in finding pregnancy 7 days.

Patients after amenorrhea need to be confirmed pregnancy by serum β-HCG detection. According to the level of serum HCG, E2 and P and clinical symptoms, corresponding tocolytic treatment will be given. At 6～8 weeks of pregnancy, patient need to be confirmed the clinical pregnancy by ultrasonography. If confirmed the clinical pregnancy (at least having one heart throb in intrauterine gestational sac), patient need to be confirmed ongoing pregnancy by ultrasonography at the 12～14 weeks of pregnancy.

In the process of the entire study, adverse events will be closely observed, and the frequency and severity of adverse events will be recorded.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 204
• Est. completion date: December 2017
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 35 Years

Eligibility

Inclusion Criteria:

1. Clinical diagnosis of endometriosis, infertility, with Syndrome of qi stagnation blood stasis pattern in TCM ;

2. The first time undergoing Laparoscopic or laparoscopy combined surgery , in lined with endometriosis-related infertility, tubal patency or obstruction lightly;

3. EFI score greater than 4 points;

4. Early follicular phase FSH=10mIU / L;

5. 28 days of the menstrual cycle ± 7 days;

6. Female patients between 20-35 years old;

7. No previous history of severe drug allergies;

8. Past Three-month no taking hormone drugs such as danazol, Gestrinone, GnRHa;

9. No severe primary brain vascular diseases, liver, kidney and hematopoietic systems diseases, no history of mental illness, no drugs, alcohol, tobacco, caffeine dependent history;

10. Have signed informed consent

Exclusion Criteria:

1. Associated with uterine fibroids, the diameter greater than 4cm, adenomyosis, pelvic tuberculosis, endometrial tuberculosis, intrauterine adhesions, polycystic ovary syndrome, hyperprolactinemia, thyroid dysfunction patients.

2. Serious history of drug allergy.

3. Male factor infertility.

4. The couple separated persons.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endometriosis
• Infertility

Intervention

Drug:
• pre-ovulation Decoction
HuoXueXiaoYi Decoction(Bupleurum 10g, Cyperus 10g, Salvia miltiorrhiza 20g, Red peony 10g,etc)has activating blood and absorbing clots effect, can inhibit the growth of ectopic endometrium, promote follicular growth, maturity, improve ovulation and the receptivity of endometrium.
• post-ovulation Decoction
BuShenZhuYun Decoction(Bupleurum 10g,Poria 15g, Atractylodes 15g,Ligustrum 15g,etc) has dredging liver and nourishing kidney effect, can improve the function of corpus luteum. All are made into granules.
• pre-ovulation Decoction(placebo)
Composition of maltodextrin, lactose, edible pigment, taste masking agent.
• post-ovulation Decoction(placebo)
Composition of maltodextrin, lactose, edible pigment, taste masking agent.

Locations

Country	Name	City	State
China	Beijing Obstetrics and Gynecology Hospital,Captial Medical University	Beijing	Beijing
China	GAMHospital	Beijing	Beijing
China	Beijng Hospital	Beijng
China	The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine	Guangzhou	Guangdong
China	Traditional Chinese Medicine Hospital of Guangdong Province	Guangzhou	Guangdong
China	The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine	Hefei	Anhui

Sponsors (6)

Lead Sponsor	Collaborator
Guang'anmen Hospital of China Academy of Chinese Medical Sciences	Beijing Hospital, Guangdong Provincial Hospital of Traditional Chinese Medicine, Peking Union Medical College Hospital, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine

Country where clinical trial is conducted

China, 

References & Publications (3)

Duffy JM, Arambage K, Correa FJ, Olive D, Farquhar C, Garry R, Barlow DH, Jacobson TZ. Laparoscopic surgery for endometriosis. Cochrane Database Syst Rev. 2014 Apr 3;4:CD011031. doi: 10.1002/14651858.CD011031.pub2. Review. — View Citation

Yap C, Furness S, Farquhar C. Pre and post operative medical therapy for endometriosis surgery. Cochrane Database Syst Rev. 2004;(3):CD003678. Review. — View Citation

Zhao RH, Hao ZP, Zhang Y, Lian FM, Sun WW, Liu Y, Wang R, Long L, Cheng L, Ding YF, Song DR, Meng QW, Wang AM. Controlling the recurrence of pelvic endometriosis after a conservative operation: comparison between Chinese herbal medicine and western medici — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Treatment-emergent Adverse Events	Treatment-emergent Adverse Events were assessed by CTCAE v4.0.	six menstrual cycles(each cycle is 28±7 days)	No
Primary	Pregnancy rate	Pregnancy rate is defined as the proportion of participants finding pregnancy after amenorrhea and confirming serumß-HCG positive.	six menstrual cycles(each cycle is 28±7 days)	No
Secondary	Clinical pregnancy rate (with intrauterine pregnancy sac)	defined as the proportion of participants confirmed there are at least one gestational sac in uterine cavity (No matter whether there is a heart throb) by ultrasonography.	at 6~8 weeks of pregnancy	No
Secondary	Clinical pregnancy rate (with a heart throb)	defined as the proportion of participants confirmed at least having one heart throb in intrauterine gestational sac by ultrasonography.	at 6~8 weeks of pregnancy	No
Secondary	Continued pregnancy rate	defined as the proportion of participants confirmed at least one live fetuses by ultrasonography.	at the 12~14 weeks of pregnancy	No