Clinical Observation on Kuntai Capsule in Treating Early-onset Ovarian Hypofunction

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of Kuntai capsule alone or combined with hormone therapy in improving ovarian function in POI patients (including subclinical stage).

Detailed Description
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The study is expected to be conducted between 2021.08 and 2023.12.120 subjects with early-onset ovarian insufficiency will be randomly assigned to trial, control, or combination groups using a computer-generated randomization table.By comparing the data of primary efficacy indexes, secondary efficacy indexes and safety indexes before and after medication, The principal investigator will write and publish the paper.

Official Title
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A Multi-center Clinical Study on the Efficacy and Safety of Kuntai Capsule Alone and in Combination With Hormones in the Treatment of Early-onset Hypoovarian Function

Conditions
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Primary Ovarian Insufficiency

Intervention / Treatment
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* Drug: Kuntai Capsule
* Drug: Femoston


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The women aged <40 years old. Serum basal follicle stimulating hormone (FSH) level ≥15 IU/L at least twice inspection (two occasions >4 weeks apart). Rare menstruation or menopause for at least 4 months. Individuals meeting the above criteria who voluntarily consented to study participation. Exclusion Criteria: Pregnant and lactating patients; Patients with endometriosis, adenomyosis, endometrial lesions (submucous fibroids, endometrial polyps, etc.), hysteromyoma > 4cm or hysterectomy; Patients with known or suspected breast cancer history and estrogen-dependent malignant tumor; Patients with personal history of venous thromboembolism (VTE) or high risk of VTE (including body mass index > 30 kg/m2, smoking and family history of thrombosis); Patients with porphyria; Patients with serious primary diseases or mental illness such as cardiovascular, liver, kidney and hematopoietic system; Patients who are participating in other clinical trials or have participated in other clinical trials in the past three months; Patients who suspect or have a history of alcohol and drug abuse; Patients who are known to be allergic to the test drugs or their components; The researchers determined that patients are not suitable for this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 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: Factorial Assignment
Interventional Model Description: Subclinical POI and POI patients
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: POI patients who taking Kuntai capsule<br>Patients in this group will take Kuntai capsule orally, 4 capsules each time, 3 times a day, and take the medicine for 3 courses. | Drug: Kuntai Capsule<br>* The instructions is pointed that each Kuntai capsule is 0.5g and the usage of Kuntai capsule is oral taking 4 capsules each time, 3 times a day, and 4 weeks is a course of treatment. The patients will taking 3 courses of treatment in this study.<br>* Other names: Kuntai Jiaonang;|
| Active Comparator: POI patients who accepting hormone therapy<br>The estrogen and progesterone sequential regimen was adopted. The drug was estradiol tablets/estradiol didroxyprogesterone tablets (Femoston). Red tablets (estradiol, 2mg/d) were taken in the first 14 days, and gray tablets (estradiol, 2mg/d, dydrogesterone,10 mg/d) were taken in the last 14 days. 28 days was a course of treatment, and 3 courses of treatment were taken. | Drug: Femoston<br>* The estrogen and progesterone sequential regimen was adopted. The Femoston was contain estradiol tablets and estradiol didroxyprogesterone tablets. Red tablets (estradiol, 2 mg/d) were taken in the first 14 days, and gray tablets (estradiol, 2 mg/d, dydrogesterone,10 mg/d) were taken in the last 14 days. 28 days was a course of treatment, and three courses of treatment were taken. The patients will taking 3 courses of treatment in this study.<br>* Other names: Complex Packing Estradiol Tablets/Estradiol and Dydrogesterone Tablets;|
| Experimental: POI patients who taking Kuntai capsule combined with hormone therapy<br>Kuntai capsule was taken at the same dose as Kuntai group on the basis of hormone therapy for 3 courses. | Drug: Kuntai Capsule<br>* The instructions is pointed that each Kuntai capsule is 0.5g and the usage of Kuntai capsule is oral taking 4 capsules each time, 3 times a day, and 4 weeks is a course of treatment. The patients will taking 3 courses of treatment in this study.<br>* Other names: Kuntai Jiaonang;Drug: Femoston<br>* The estrogen and progesterone sequential regimen was adopted. The Femoston was contain estradiol tablets and estradiol didroxyprogesterone tablets. Red tablets (estradiol, 2 mg/d) were taken in the first 14 days, and gray tablets (estradiol, 2 mg/d, dydrogesterone,10 mg/d) were taken in the last 14 days. 28 days was a course of treatment, and three courses of treatment were taken. The patients will taking 3 courses of treatment in this study.<br>* Other names: Complex Packing Estradiol Tablets/Estradiol and Dydrogesterone Tablets;|
| Experimental: Subclinical POI patients who taking Kuntai capsule<br>Subclinical POI patients in this group which with Kuntai capsule intervention. This group is a self-controlled experiment before and after treatment | Drug: Kuntai Capsule<br>* The instructions is pointed that each Kuntai capsule is 0.5g and the usage of Kuntai capsule is oral taking 4 capsules each time, 3 times a day, and 4 weeks is a course of treatment. The patients will taking 3 courses of treatment in this study.<br>* Other names: Kuntai Jiaonang;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Follicle-stimulating hormone (FSH) | Changes of the level of FSH before and after treatment | Baseline, 3 months, 6 months | 
| Kupperman Score | Changes of the Kupperman score before and after treatment，Kupperman Score ranges from 0 to 69, with the smaller the score, the better off the subject | Baseline, 3 months, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Luteinizing hormone (LH) | Changes of the level of LH before and after treatment | Baseline, 3 months, 6 months | 
| Estradiol hormone (E2) | Changes of the level of Estradiol hormone before and after treatment | Baseline, 3 months, 6 months | 
| Antral follicle count (AFC) | Changes of the AFC before and after treatment | Baseline, 3 months, | 
| anti-Müllerian hormone (AMH) | Changes of the level of AMH before and after treatment | Baseline, 3 months, | 
| The peak systolic blood flow velocity （PSV） | The peak systolic blood flow velocity before and after treatment was assessed by vaginal B ultrasound | Baseline, 3 months, | 
| The end-diastolic blood flow velocity（EDV） | The uterine artery end-diastolic blood flow velocity before and after treatment was assessed by vaginal B ultrasound | Baseline, 3 months, | 
| Uterine artery resistance index（RI） | The uterine artery resistance index before and after treatment was assessed by vaginal B ultrasound | Baseline, 3 months, | 
| Proportion of patients with normal menstruation | To measure the ratio of patients have normal menstruation after treatment | Baseline，3 months, 6 months, 9 months | 
| Pregnancy situation | To ask the patient if there is pregnancy (for patient who has pregnancy need) | 6 months |