## Protocol Section
### Identification Module
**NCT ID:** NCT06423235

**Acronym:** ESPTTN

**Brief Title:** Efficacy and Safety of Prunella Oral Liquid in the Treatment of Thyroid Nodules

**Official Title:** Efficacy and Safety of Prunella Oral Liquid in the Treatment of Thyroid Nodules: a Multicenter, Prospective, Randomized, Double-blind, Placebo-controlled Study

#### Organization Study ID Info
**ID:** XK-22-A-002-YJ-002
#### Organization
**Class:** INDUSTRY
**Full Name:** Xintian Pharmaceutical
### Status Module
#### Completion Date
**Date:** 2028-07-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-21

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-15

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-07-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-30

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-21
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-07
**Study First Submit QC Date:** 2024-05-15
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Xintian Pharmaceutical

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** A multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of Prunella oral liquid in patients with benign thyroid nodules, which belongs to the post-marketing reevaluation clinical study.

In this study, 426 subjects will be enrolled by competitive enrollment at several research centers across China. The main inclusion criteria are:

① Thyroid ultrasound examination found thyroid nodules, can be accompanied by goiter, and the nodules meet the following conditions: 1) There were dominant nodules in single or multiple nodules (the largest diameter of the second largest nodules was not more than 50% of the largest nodules), 2) solid nodules, 3) the longest diameter of nodules was ≥1cm and \< 3cm, 4) C-TIRADS 3\~4A nodules.

② Patients who met the puncture indication were confirmed by fine needle aspiration biopsy (FNAB) as benign nodules (Bethesda II).

③ Levels of TSH, FT3 and FT4 were normal, and the antibody titers of TgAb and TPOAb were normal.

Eligible subjects will be randomly assigned on a 1:1:2:2 scale to: Group A (placebo conventional dose group, 10 mL/times, 2 times/day), group B (placebo 2x dose group, 10ml/times, 2 times/day), group C (conventional dose group of Prunella oral liquid), group D (Prunella oral liquid 2x dose group). All subjects will receive the treatment for 9 months and follow up at 3rd, 6th, 9th and 12th month.

The primary efficacy endpoint of this study was the rate of change in thyroid nodule volume from baseline at 6 months of treatment. The rate of change in thyroid nodule volume from baseline at 3 and 9 months of treatment was a secondary efficacy endpoint. Other secondary efficacy endpoints included maximum thyroid nodule diameter, number of thyroid nodules, proportion of patients with reduced thyroid nodule volume or ≥50% from baseline, thyroid volume, thyroid function (serum TSH, FT3, FT4, thyroid egg levels (Tg), thyroid antibody levels (TgAb, TPOAb), quality of life evaluation (SF-36), etc. Safety endpoints included incidence of AE/ serious adverse events (SAE), causality, and outcomes. Incidence of AE/SAE leading to discontinuation. Changes in safety laboratory test values from baseline.

### Conditions Module

**Conditions:**

- Thyroid Nodule

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** DOUBLE

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 426

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: regular dose of placebo

**Label:** placebo regular dose group

**Type:** PLACEBO_COMPARATOR

#### Arm Group 2

**Intervention Names:**

- Drug: 2x regular dose of placebo

**Label:** placebo 2x regular dose group

**Type:** PLACEBO_COMPARATOR

#### Arm Group 3

**Intervention Names:**

- Drug: regular dose of JiRui® Prunella oral liquid

**Label:** regular dose group of Prunella oral liquid group

**Type:** ACTIVE_COMPARATOR

#### Arm Group 4

**Intervention Names:**

- Drug: 2x regular dose of JiRui® Prunella oral liquid

**Label:** 2x regular dose group of Prunella oral liquid group

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- regular dose group of Prunella oral liquid group

**Description:** Take 10ml twice a day

**Name:** regular dose of JiRui® Prunella oral liquid

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- 2x regular dose group of Prunella oral liquid group

**Description:** Take 20ml twice a day

**Name:** 2x regular dose of JiRui® Prunella oral liquid

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- placebo regular dose group

**Description:** Take 10ml twice a day

**Name:** regular dose of placebo

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- placebo 2x regular dose group

**Description:** Take 20ml twice a day

**Name:** 2x regular dose of placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Rate of change in thyroid nodule volume from baseline at 6 months of treatment.

**Time Frame:** 180 ± 10 days

#### Secondary Outcomes

**Measure:** Rate of change in thyroid nodule volume from baseline at 3 months of treatment.

**Time Frame:** 90 ± 7 days.

**Measure:** Rate of change in thyroid nodule volume from baseline at 9 months of treatment.

**Time Frame:** 270 ± 14 days.

**Measure:** Rate of change in thyroid nodule volume from baseline at 12 months of treatment.

**Time Frame:** 360 ± 14 days.

**Measure:** The change value of the maximum diameter of thyroid nodules from baseline at 3 months of treatment.

**Time Frame:** 90 ± 7 days

**Measure:** The change value of the maximum diameter of thyroid nodules from baseline at 6 months of treatment.

**Time Frame:** 180 ± 10 days

**Measure:** The change value of the maximum diameter of thyroid nodules from baseline at 9 months of treatment.

**Time Frame:** 270 ± 14 days

**Measure:** The change value of the maximum diameter of thyroid nodules from baseline at 12 months of treatment.

**Time Frame:** 360 ± 14 days

**Measure:** Proportion of patients with reduced thyroid nodule volume from baseline at 3 months of treatment.

**Time Frame:** 90 ± 7 days

**Measure:** Proportion of patients with reduced thyroid nodule volume from baseline at 6 months of treatment.

**Time Frame:** 180 ± 10 days

**Measure:** Proportion of patients with reduced thyroid nodule volume from baseline at 9 months of treatment.

**Time Frame:** 270 ± 14 days

**Measure:** Proportion of patients with reduced thyroid nodule volume from baseline at 12 months of treatment.

**Time Frame:** 360 ± 14 days

**Measure:** Proportion of patients with reduced thyroid nodule volume ≥50% from baseline at 3 months of treatment.

**Time Frame:** 90 ± 7 days

**Measure:** The proportion of patients with reduced thyroid nodule volume ≥50% from baseline at 6 months of treatment.

**Time Frame:** 180 ± 10 days

**Measure:** Proportion of patients with reduced thyroid nodule volume ≥50% from baseline at 9 months of treatment.

**Time Frame:** 270 ± 14 days

**Measure:** Proportion of patients with reduced thyroid nodule volume ≥50% from baseline at 12 months of treatment.

**Time Frame:** 360 ± 14 days

**Measure:** Changes in the number of thyroid nodules from baseline at the 3 months of treatment.

**Time Frame:** 90 ± 7 days

**Measure:** Changes in the number of thyroid nodules from baseline at the 6 months of treatment.

**Time Frame:** 180 ± 10 days

**Measure:** Changes in the number of thyroid nodules from baseline at the 9 months of treatment.

**Time Frame:** 270 ± 14 days

**Measure:** Changes in the number of thyroid nodules from baseline at the 12 months of treatment.

**Time Frame:** 360 ± 14 days

**Measure:** Proportion of patients with thyroid nodule progression (greater than 50% in volume or greater than 20% in at least 2 diameters from baseline) at 3 months of treatment.

**Time Frame:** 90 ± 7 days

**Measure:** Proportion of patients with thyroid nodule progression (greater than 50% in volume or greater than 20% in at least 2 diameters from baseline) at 6 months of treatment.

**Time Frame:** 180 ± 10 days

**Measure:** Proportion of patients with thyroid nodule progression (greater than 50% in volume or greater than 20% in at least 2 diameters from baseline) at 9 months of treatment.

**Time Frame:** 270 ± 14 days

**Measure:** Proportion of patients with thyroid nodule progression (greater than 50% in volume or greater than 20% in at least 2 diameters from baseline) at 12 months of treatment.

**Time Frame:** 360 ± 14 days

**Measure:** Rate of change in thyroid volume from baseline at 3 months of treatment.

**Time Frame:** 90 ± 7 days

**Measure:** Rate of change in thyroid volume from baseline at 6 months of treatment.

**Time Frame:** 180 ± 10 days

**Measure:** Rate of change in thyroid volume from baseline at 9 months of treatment.

**Time Frame:** 270 ± 14 days

**Measure:** Rate of change in thyroid volume from baseline at 12 months of treatment.

**Time Frame:** 360 ± 14 days

**Measure:** Changes in serum TSH, FT3 and FT4 from baseline at the months of treatment.

**Time Frame:** 90 ± 7 days

**Measure:** Changes in serum TSH, FT3 and FT4 from baseline at the months of treatment.

**Time Frame:** 180 ± 10 days

**Measure:** Changes in serum TSH, FT3 and FT4 from baseline at 9 months of treatment.

**Time Frame:** 270 ± 14 days

**Measure:** Changes in serum TSH, FT3 and FT4 from baseline at 12 months of treatment.

**Time Frame:** 360 ± 14 days

**Measure:** Changes in Tg, TgAb and TPOAb levels from baseline at the 6th month of treatment.

**Time Frame:** 180 ± 10 days

**Measure:** Proportion of patients with normal thyroid function at 3 months of treatment.

**Time Frame:** 90 ± 7 days

**Measure:** Proportion of patients with normal thyroid function at 6 months of treatment.

**Time Frame:** 180 ± 10 days

**Measure:** Proportion of patients with normal thyroid function at 9 months of treatment.

**Time Frame:** 270 ± 14 days

**Measure:** Proportion of patients with normal thyroid function at 12 months of treatment.

**Time Frame:** 360 ± 14 days

**Measure:** Subjects' quality of life scores (SF-36) at 3 months of treatment.

**Time Frame:** 90 ± 7 days

**Measure:** Subjects' quality of life scores (SF-36) at 6 months of treatment.

**Time Frame:** 180 ± 10 days

**Measure:** Subjects' quality of life scores (SF-36) at 9 months of treatment.

**Time Frame:** 270 ± 14 days

**Measure:** Subjects' quality of life scores (SF-36) at 12 months of treatment.

**Time Frame:** 360 ± 14 days

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* 18 years old ≤65 years old;
* Thyroid ultrasonography found thyroid nodules, may be accompanied by goiter, and the nodules meet the following conditions: 1) single nodules, or dominant nodules in multiple nodules (the largest diameter of the second largest nodules does not exceed 50% of the largest nodules), 2) solid nodules, 3) the longest diameter of nodules ≥1cm and \< 3cm, 4) C-TIRADS 3\~4A nodules;
* Patients who met the puncture indications were confirmed by fine needle aspiration biopsy (FNAB) as benign nodules (Bethesda Class II);
* Serum TSH, free thyroid hormone (FT3, FT4) levels were normal, anti-thyroglobulin (TgAb) and anti-thyroid peroxidase (TPOAb) antibody titers were normal;
* Meet the diagnostic criteria of thyroid nodules in TCM;
* Sign the informed consent.

Exclusion Criteria:

* Exclude the patients with Deficiency of Yang syndrome, and the following two conditions can be diagnosed: Shortness of breath, abdominal pain and diarrhea, diarrhea with undigested food, Insufficiency with chills, exhaustion and lethargy, pale tongue and white fur, deep and weak pulse
* Those who have reproductive needs during pregnancy, lactation and within the last 12 months;
* Patients with high possibility of thyroid cancer indicated by ultrasonic signs and malignant confirmed by fine needle biopsy;
* Patients who meet the indications for thyroid nodule surgery, such as local compression symptoms obviously related to the nodule, the tumor is located behind the sternum or in the mediastinum, or strongly require surgery due to appearance or ideological concerns affecting normal life;
* Patients who have taken prunella preparations or other similar Chinese medicines to treat the disease within the past 1 month; Patients using glucocorticoids in the last 3 months;
* Patients who have had or plan to take thyroid hormone, iodine compound, or antithyroid drug therapy during the study period;
* Patients who have previously or plan to undergo ablation, neck radiation, surgery and other non-drug treatments during the study period;
* Patients with parathyroid tumor (PTA), medullary thyroid cancer (MTC) or other malignant tumors, or patients with serious cardiovascular disease, liver and kidney disease, osteoporosis, or patients with a history of mental illness;
* Patients with a family history of thyroid cancer or thyroid cancer syndrome;
* Laboratory test index ALT, AST \> 1.5 times the upper limit of reference value or blood creatinine (Scr) \> the upper limit of reference value;
* Persons who are known to be allergic to the investigational drug or its ingredients;
* Other patients determined by the investigator to be unsuitable for participation in the study.

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** yx-jiwj@xtyyoa.com

**Name:** Wenjing Ji

**Phone:** +86 18365572279

**Role:** CONTACT

**Contact 2:**

**Email:** ht-cb@xtyyoa.com

**Name:** Biao Chen

**Phone:** +86 13915637727

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Chongqing

**Contacts:**

***Contact 1:***

- **Name:** Hongting Zheng

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Second Hospital of Army Military Medical University

**State:** Chongqing

**Location 2:**

**City:** Xiamen

**Contacts:**

***Contact 1:***

- **Name:** Tianchi Hu

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Xiamen Hospital of Traditional Chinese Medicine

**State:** Fujian

**Location 3:**

**City:** Guangzhou

**Contacts:**

***Contact 1:***

- **Phone:** （020）83827812

- **Role:** CONTACT

***Contact 2:***

- **Name:** Haixia Guan

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** People's Hospital of Guangdong Province

**State:** Guangdong

**Location 4:**

**City:** Shenzhen

**Contacts:**

***Contact 1:***

- **Name:** Fan Zhang

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Shenzhen Hospital of Peking University

**State:** Guangdong

**Location 5:**

**City:** Shunde

**Contacts:**

***Contact 1:***

- **Phone:** 0757-22318000

- **Role:** CONTACT

***Contact 2:***

- **Name:** Jie Shen

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Shunde Hospital of Southern Medical University

**State:** Guangdong

**Location 6:**

**City:** Wuhan

**Contacts:**

***Contact 1:***

- **Name:** Mingsong Gao

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Wuhan First Hospital

**State:** Hubei

**Location 7:**

**City:** Nanjing

**Contacts:**

***Contact 1:***

- **Name:** Chao Liu

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Jiangsu Province Hospital of Integrated Chinese and Western Medicine

**State:** Jiangsu

**Location 8:**

**City:** Xuzhou

**Contacts:**

***Contact 1:***

- **Name:** Hongwei Lin

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Xuzhou Medical University Hospital

**State:** Jiangsu

**Location 9:**

**City:** Dalian

**Country:** China

**Facility:** The Second Hospital of Dalian Medical University

**State:** Liaoning

**Location 10:**

**City:** Shenyang

**Contacts:**

***Contact 1:***

- **Name:** Yuqing Li

- **Phone:** +86 15140139773

- **Role:** CONTACT

***Contact 2:***

- **Name:** Zhongyan Shan

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** China

**Facility:** The First Hospital of China Medical University

**State:** Liaoning

**Zip:** 200032

**Location 11:**

**City:** Shenyang

**Contacts:**

***Contact 1:***

- **Phone:** 82961387

- **Role:** CONTACT

***Contact 2:***

- **Name:** Tianshu Gao

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Hospital of Liaoning University of Chinese Medicine

**State:** Liaoning

**Location 12:**

**City:** Shenyang

**Contacts:**

***Contact 1:***

- **Phone:** 024-24016001

- **Role:** CONTACT

***Contact 2:***

- **Name:** Binhong Wen

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** People's Hospital of Liaoning Province

**State:** Liaoning

**Location 13:**

**City:** Qingdao

**Contacts:**

***Contact 1:***

- **Name:** Jie Zhu

- **Role:** CONTACT

***Contact 2:***

- **Name:** Yangang Wang

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** China

**Facility:** The First Hospital of Qingdao University

**State:** Shandong

**Location 14:**

**City:** Weifang

**Contacts:**

***Contact 1:***

- **Phone:** 963360

- **Role:** CONTACT

***Contact 2:***

- **Name:** Haixia Liu

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Weifang People's Hospital

**State:** Shandong

**Location 15:**

**City:** Weihai

**Contacts:**

***Contact 1:***

- **Phone:** 0631-5287120

- **Role:** CONTACT

***Contact 2:***

- **Name:** Yachao Yang

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Weihai Hospital

**State:** Shandong

**Location 16:**

**City:** Shanghai

**Contacts:**

***Contact 1:***

- **Phone:** 02163864050-510905

- **Role:** CONTACT

***Contact 2:***

- **Name:** Dongjie Shen

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine

**State:** Shanghai

**Location 17:**

**City:** Shanghai

**Contacts:**

***Contact 1:***

- **Name:** Shen Qu

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Shanghai 10th People's Hospital

**State:** Shanghai

**Location 18:**

**City:** Shanghai

**Contacts:**

***Contact 1:***

- **Name:** Yongde Peng

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Shanghai First People's Hospital

**State:** Shanghai

**Location 19:**

**City:** Shanghai

**Contacts:**

***Contact 1:***

- **Name:** Jin'an Zhang

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Shanghai Pudong Zhoupu Hospital

**State:** Shanghai

**Location 20:**

**City:** Kunming

**Contacts:**

***Contact 1:***

- **Name:** Heng Su

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** First People's Hospital of Yunnan Province

**State:** Yunnan

**Location 21:**

**City:** Kunming

**Contacts:**

***Contact 1:***

- **Phone:** 0871-65324888

- **Role:** CONTACT

***Contact 2:***

- **Name:** Yushan Xu

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** The First Hospital of Kunming Medical University

**State:** Yunnan

**Location 22:**

**City:** Hangzhou

**Contacts:**

***Contact 1:***

- **Name:** Xin Mu

- **Role:** SUB_INVESTIGATOR

**Country:** China

**Facility:** Zhejiang Province Hospital of Integrated Chinese and Western Medicine

**State:** Zhejiang

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004700

- Term: Endocrine System Diseases

- ID: D000013964

- Term: Thyroid Neoplasms

- ID: D000004701

- Term: Endocrine Gland Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000006258

- Term: Head and Neck Neoplasms

### Condition Browse Module - Browse Branches

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC04

- Name: Neoplasms

### Condition Browse Module - Browse Leaves

- ID: M16718

- Name: Thyroid Diseases

- Relevance: HIGH

- As Found: Thyroid

- ID: M18986

- Name: Thyroid Nodule

- Relevance: HIGH

- As Found: Thyroid Nodules

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M16723

- Name: Thyroid Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7863

- Name: Endocrine Gland Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M9348

- Name: Head and Neck Neoplasms

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000016606

- Term: Thyroid Nodule

- ID: D000013959

- Term: Thyroid Diseases

### Misc Info Module

- Version Holder: 2024-05-31
