Efficacy and Safety of Dingkundan Combined With Combination Oral Contraceptives in the Treatment of PCOS: an Open-label, Non-randomized Controlled Clinical Study

Study Overview
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Brief Summary
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This is a single-center, non-randomized, open-label clinical study to investigate the efficacy and safety of Dingkundan (DKP) combined with compound oral contraceptives (COC) in the treatment of PCOS. This study is mainly to compare the effect of COC plus DKP verse COC on reducing androgen, improving the function of ovarian and the individual metabolism. The secondary objective of our study is to explore the efficacy of DKP on pregnancy in patients with PCOS and its safety.

Detailed Description
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In this study, the decreased level of serum androgen was used as the main outcome index. It was assumed that PCOS patients treated with Dingkundan combined with compound oral contraceptives for 3 menstrual cycles had decreased serum androgen by 0.53nmol/L. It was assumed that the serum androgen decreased by 0.21nmol/L after 3 menstrual cycles of combined oral contraceptives alone. If α = 0.05, the test degree was 80%, and the dropout rate of 20%, considering that the sample size ratio between the experimental group and control group was 1, the sample size of experimental group and control group were 60 cases each, and 120 cases in total. All the samples were recruited from the Department of Gynecology and Women's Health Care of Guangdong Women and Children's Health Hospital. This study was approved by the Ethics Committee of the hospital, and all participants are required to sign informed consent. Before the study, researchers should be trained in a unified and standardized manner, including medication methods, observation indicators, judgment and treatment of adverse reactions/events, and reporting of serious adverse events. The researcher must adequately and accurately record the research process so that the research data can be verified. These records can be divided into two categories: study documents and raw patient data. Study documents include protocols and amendments, sample informed consent forms, researcher resumes and authorization forms, and other required documents and correspondence. Original documents of patients' include patient inpatient/outpatient records, doctor's and nurse's orders, appointment dates, original laboratory reports, ultrasound, signed informed consent forms, patient screening forms, etc. During the study period, if the subject withdraws the informed consent, or refuses the further follow-up, or loses follow-up, or dies, the sample will be disqualified. If the subject withdraws consent, refuses to continue the study, or the investigator determines that the subject's clinical symptoms/physical condition has worsened and that the subject is no longer suitable for the study, or the subject develops toxicity intolerance, such as any clinical AE, laboratory abnormalitiesor, or the investigator determines that the subject has reached the study endpoint, or any circumstances warrant discontinuation of this study judged by the investigator, or the study sponsor discontinues the study, this study will be stop. Anyway, this clinical study is conducted in accordance with the Declaration of Helsinki and relevant regulations on clinical trials in China. It can only be carried out after obtaining the approval of the Ethics Committee. The modification of clinical research protocols, informed documents and other materials involved in clinical research should be approved by the Ethics Committee before implementation. The investigator should protect the rights and privacy of the subject.

Official Title
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Efficacy and Safety of Dingkundan Combined With Combination Oral Contraceptives in the Treatment of PCOS: an Open-label, Non-randomized Controlled Clinical Study

Conditions
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PCOS

Intervention / Treatment
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* Drug: DingKunDan(GuangYuYuan)
* Drug: Drospirenone and Ethinylestradiol Tablets (Ⅱ)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women diagnosed with PCOS. Aged from 18 to 35 years old, in the reproductive age. Have not taken any hormone or Chinese medicine in the past 3 months. Exclusion Criteria: Age < 18 years or > 35 years. Have taken hormones or Chinese medicine in the last 3 months. Have congenital adrenal hyperplasia, Cushing's syndrome, or androgen-secreting tumors. Abnormal function of liver and kidney. Have hrombotic disease, arterial or venous thromboembolism, or major organic disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with DingKunDan(GuangYuYuan) combined with compound oral contraceptives<br>This arm is treated with DingKunDan plus compound oral contraceptives: Drospirenone and Ethinylestradiol Tablets (Ⅱ). | Drug: DingKunDan(GuangYuYuan)<br>* The experimental group would be given DingKunDan, the subjects should take 3.5g each time, twice a day. Subjects in the control group only needed to take COC. Both groups take medicine for 3 months consecutively as a course of treatment.<br>* Other names: Drospirenone and Ethinylestradiol Tablets (Ⅱ): H20140972;Drug: Drospirenone and Ethinylestradiol Tablets (Ⅱ)<br>* The experimental group and the control group would be given oral Drospirenone and Ethinylestradiol Tablets (Ⅱ). According to the packaging instructions, on the first day of menstruation, according to the packaging instructions, the subjects should take the tablet, then take the rest sequential at the same time every day for 28 consecutive days, menstruation would happen after drug withdrawal (or after 7 days of drug withdrawal), and the next medication cycle begin on the first day of menstruation.<br>* Other names: Drospirenone and Ethinylestradiol Tablets (Ⅱ): H20140972;|
| Active Comparator: Treatment with compound oral contraceptives<br>This arm is only treated with compound oral contraceptives: Drospirenone and Ethinylestradiol Tablets (Ⅱ). | Drug: DingKunDan(GuangYuYuan)<br>* The experimental group would be given DingKunDan, the subjects should take 3.5g each time, twice a day. Subjects in the control group only needed to take COC. Both groups take medicine for 3 months consecutively as a course of treatment.<br>* Other names: Drospirenone and Ethinylestradiol Tablets (Ⅱ): H20140972;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum androgen | Basic serum androgen is one of the primary outcome measure and is aim to evaluate the efficacy of Dingkundan that as an adjuvant therapy for PCOS. | Before inclusion；after one treatment course. | 
| Free testosterone | Free testosterones is one of the primary outcome measureis aim to evaluate the efficacy of Dingkundan that as an adjuvant therapy for PCOS. | Before inclusion；after one treatment course. | 
| Androstenedione | Androstenedione is one of the primary outcome measure is aim to evaluate the efficacy of Dingkundan that as an adjuvant therapy for PCOS. | Before inclusion；after one treatment course. | 
| sex hormone-binding globulin（SHBG） | SHBG is one of the primary outcome measure is aim to evaluate the efficacy of Dingkundan that as an adjuvant therapy for PCOS. | Before inclusion；after one treatment course. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting blood-glucose (FBG) | This outcome measure is aim to assess if Dingkundan is a useful adjuvant therapy for PCOS in improving metabolism. | Before inclusion；after one treatment course. | 
| Fasting insulin (FINS) | This outcome measure is aim to assess if Dingkundan is a useful adjuvant therapy for PCOS in improving metabolism. | Before inclusion；after one treatment course. | 
| HOMA-IR | HOMA-IR is used to assess the level of insulin resistance and help to evaluate the metabolism of individuals. | Before inclusion；after one treatment course. | 
| Anti-Müllerian hormone (AMH) | AMH is an important index to evaluate AMH is an important index to evaluate the reserve function of ovarian. | Before inclusion；after one treatment course. | 
| HCY | HCY is used to assess the level of folate metabolism | Before inclusion；after one treatment course. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dingkundan(DKP), Compound Oral Contraceptives(COC), PCOS