The Effect of Chinese Herbal Medicine for Reducing the Application of Antibiotics in the Treatment of Acute Mastitis

Study Overview
=================
Brief Summary
-----------------
The object of the study is to evaluate the effect of Pugongying (Herba Taraxaci) Granules to reduce the application of antibiotics for women with acute mastitis.

Detailed Description
-----------------
Acute mastitis affects the health and quality of life of the infants and mothers during the lactation. Increasing studies indicate that bacterial infections and/or dysbacteriosis are essential to the mechanisms of the disease. Thus, antibiotics is widely used in clinical practice, especially cephalosporin in China. However, mistaking antibiotic will affect the physical function, even mothers' breastfeeding. The previous clinical trial that the investigators had conducted in the Third affiliated hospital of Beijing University of Chinese Medicine, has demonstrated that Chinese herbal medicine can act better than Cefdinir in the fever-relief time and breast pain scores. Some studies the investigators searched in the databases have showed that Pugongying (Herba Taraxaci) has a broad spectrum of antimicrobial activity, and it can regulate dysbacteriosis. At the same time, Pugongying (Herba Taraxaci) can also promote the secretion of milk and maintain the patency of milk well. The main ingredient of Pugongying (Herba Taraxaci) Granules is Pugongying herbs (Herba Taraxaci). Pugongying (Herba Taraxaci) Granules is approved by China Food and Drug Administration (CFDA) to treat acute mastitis. Although Pugongying (Herba Taraxaci) Granules is widely used in clinical practice, there is no trial to test the efficacy of Pugongying (Herba Taraxaci) for women with acute mastitis. Therefore, the investigators set three groups with Pugongying (Herba Taraxaci) Granules alone, Cefdinir alone and combination of Pugongying (Herba Taraxaci) Granules and Cefdinir.

Official Title
-----------------
The Effect of Chinese Herbal Medicine for Reducing the Application of Antibiotics in the Treatment of Acute Mastitis With Three Groups in Randomized Controlled Trial.

Conditions
-----------------
Mastitis Acute Female

Intervention / Treatment
-----------------
* Drug: CHPM (Chinese Herbal Patent Medicine )
* Drug: Antibiotics Cefdinir Capsules
* Behavioral: Education
* Drug: Antibiotics Cefdinir Capsules


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women in lactation who have strong willing to breastfeeding; The course of acute mastitis should be within 3 days, and the ultrasound examination indicates there is no abscess cavity formed; The body temperature is higher than 37.2°C but lower than 41°C; The VAS scores of participants≥4; Patients with acute mastitis have not received other medical therapies; Those who have signed informed consent. Exclusion Criteria: Participants who suffered nipple ulceration, painful fissuring or developmental defects fail to breastfeed; Participants with other breast diseases are not appropriate to breastfeed; Participants with severe cognitive or metabolic diseases will affect breastfeeding; Participants who have been allergic to penicillin and cephalosporin.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Based on previous studies, considering the 20% expulsion rate, the investigators plan to recruit 306 participants with sample-size calculation formula. The sequence of randomization (1:1:1) will be generated by the statisticians with a computer program.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHPM (Chinese Herbal Patent Medicine )<br>CHPM (Chinese Herbal Patent Medicine ): Pugongying (Herba Taraxaci) Granules, 15g/tid for 3 days, follow-up for 7 days. Education, basic medical order. | Drug: CHPM (Chinese Herbal Patent Medicine )<br>* Pugongying (Herba Taraxaci) granules is named as Pugongying Granules in China and produced by Kunming pharmaceutical factory co. LTD. The form is granules, and the participants will take the medicine after dissolved as 15g/tid for 3 days, and the investigators will follow them up for 7 days when the participants are stopped administrating.<br>* Other names: Pugongying (Herba Taraxaci) Granules;Behavioral: Education<br>* Doctors will give suggestions and the medical orders to all participants, including dietary, emotional regulation and the knowledge of breast-feeding.<br>* Other names: Medical order;|
| Experimental: CHPM & Antibiotics Cefdinir Capsules<br>CHPM (Chinese Herbal Patent Medicine): Pugongying (Herba Taraxaci) granules, 15g/tid for 3 days, follow-up for 7 days. Antibiotics: Cefdinir Capsules, 0.1g/tid for 2 days, follow-up for 7 days. Education, basic medical order. | Drug: CHPM (Chinese Herbal Patent Medicine )<br>* Pugongying (Herba Taraxaci) granules is named as Pugongying Granules in China and produced by Kunming pharmaceutical factory co. LTD. The form is granules, and the participants will take the medicine after dissolved as 15g/tid for 3 days, and the investigators will follow them up for 7 days when the participants are stopped administrating.<br>* Other names: Pugongying (Herba Taraxaci) Granules;Behavioral: Education<br>* Doctors will give suggestions and the medical orders to all participants, including dietary, emotional regulation and the knowledge of breast-feeding.<br>* Other names: Medical order;Drug: Antibiotics Cefdinir Capsules<br>* Cefdinir Capsules is also named as Cefdinir and produced by Astellas Pharma Inc. The form is capsule, and participants will take orally the capsules with water as 0.1g/tid for 2 days, and the investigators will follow them up for 7 days when the participants are stopped administrating.<br>* Other names: Cefdinir Capsules of short course group;|
| Active Comparator: Antibiotics Cefdinir Capsules<br>Antibiotics: Cefdinir Capsules, 0.1g/tid for 3 days, follow-up for 7 days. Education, basic medical order. | Drug: Antibiotics Cefdinir Capsules<br>* Cefdinir Capsules is also named as Cefdinir and produced by Astellas Pharma Inc. The form is capsule, and participants will take orally the capsules with water as 0.1g/tid for 3 days, and the investigators will follow them up for 7 days when the participants are stopped administrating.<br>* Other names: Cefdinir Capsules of normal course group;Behavioral: Education<br>* Doctors will give suggestions and the medical orders to all participants, including dietary, emotional regulation and the knowledge of breast-feeding.<br>* Other names: Medical order;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of fever-relief | Body temperature will be measured by mercury thermometer and recorded on the prepared card by participants. The temperature of the participants reduces to 37.2℃ or more below, assessing as the normal temperature. And the normal temperature last for at least 24 hours, considered as fever-relief. To evaluate the effect of drug action time and the temperature changing from the baseline to the end of 3-day treatment. | Measured from the beginning to the end of the treatment, every 4 hours for 3 days, total 19 times including the baseline measured, specifically on 2:00 am, 6:00 am, 10:00 am, 14:00 pm, 18:00 pm, 22:00 pm. | 
| Change of the sores of breast pain | Pain of breast will be self-reported by participants and recorded. A visual analog scale (VAS) is used to assess breast pain. The scale was tested in the investigator's previous trial. 0 score indicates no uncomfortable feeling. 1-3 indicates mild uncomfortable feeling. 4-6 indicates moderate uncomfortable feeling. 7-10 indicates severe uncomfortable feeling. To evaluate the changing from the baseline to the end of 3-day treatment. | Measured from the beginning to the end of the treatment, every 8 hours for 3 days, total 10 times including the baseline measured, specifically measured on 6:00 am, 14:00 pm, 22:00 pm. | 
| Change of the area of the breast masses | The masses are manual outlined by the outcome assessor. To evaluate the changing from the baseline to the end of 3-day treatment. | The masses will be measured from the beginning to the end of the treatment, once a day for 3 days, and recorded with a camera, total 4 times including the baseline measured. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The patency of milk | The 0-3 scores are used to describe the patency of milk from no stagnation to severe stagnation. 0 indicates that there is no stagnation with breast and milk spurts out by slightly pressure; 1 indicates mild stagnation and milk flows by more pressure; 2 indicates moderate stagnation and milk drops out by much more pressure; 3 indicates there is severe stagnation and no milk excreted. The outcome will be measured by the outcome assessor. To evaluate the changing from the baseline to the end of 3-day treatment. | The outcome will be measured from the beginning to the end of the treatment, once a day for 3 days, total 4 times including the baseline measured. | 
| The scores of Traditional Chinese Medicine (TCM) symptoms | The assessment criteria refer to Standard of diagnosis and treatment in TCM symptoms (2016 version, released by State Administration of Traditional Chinese Medicine of the People's Republic of China). The outcome is specifically used to assess the holistic physical status of the participants and will be measured by TCM practitioners. To evaluate the changing from the baseline to the end of 3-day treatment. | Measured from the beginning to the end of the treatment, once a day for 3 days, total 4 times including the baseline measured. | 
| Change of the White blood cell count | Measured by the routine blood test. To evaluate the changing from the baseline to the end of 3-day treatment. | Routine blood test will be tested and analyzed by laboratory at the beginning since enrolling and after 3-day treatment. | 
| Change of the percentage of neutrophil | Measured by the routine blood test. To evaluate the changing from the baseline to the end of 3-day treatment. | Routine blood test will be tested and analyzed by laboratory at the beginning since enrolling and after 3-day treatment. | 
| Change of the C-reactive protein. | Measured by the routine blood test. To evaluate the changing from the baseline to the end of 3-day treatment. | Routine blood test will be tested and analyzed by laboratory at the beginning since enrolling and after 3-day treatment. | 
| Number of participants with treatment-related adverse events | Adverse events are assessed by CTCAE (version 5.0, released by NIH and NIC). The outcomes measured at baseline are used to determine whether the participants are eligible to participate the study and the outcomes measured during and after 3-day treatment are used to assess the safety of the intervention medicine and to protect the rights of the participants. To focus on (1) allergic reaction; (2) the vital signs: resting heart rate in times/minutes, respiratory rate in times/minutes and blood pressure in mmHg; (3) laboratory test: urinalysis (LEU, BLO, KET, NIH, GLU, PRO, UBG, SG) in positive/negative, stool routine (Sed occult blood) in postive/negative, electrocardiogram in normal/abnormal, liver function test (AST, ALT, TBIL, DBIL, TG, GLU) in positive/negative and renal function test (CR, UA, UREA) in positive/negative. To observe the incidence of the adverse events. | Symptoms of allergic reaction will be observed at any time. Signs examination will be taken once a day, for 3 days, total 4 times including the baseline measured. Laboratory test will be taken at the beginning since enrolling and after 3-day treatment. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pugongying, Herba Taraxaci, Acute Mastitis, Cefdinir, Randomized controlled trial, Postpartum, Breastfeeding, Lactation, multicenter, Chinese herb, Traditional Chinese medicine, Cephalosporin, Antibiotics