Efficacy and Safety of Prunella Oral Liquid in the Treatment of Thyroid Nodules: a Multicenter, Prospective, Randomized, Double-blind, Placebo-controlled Study
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 234
- 试验地点
- 22
- 主要终点
- Rate of change in thyroid nodule volume from baseline at 9 months of treatment.
研究概览
简要总结
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, 234 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 9 months of treatment. The rate of change in thyroid nodule volume from baseline at 3 and 6 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
placebo regular dose group
干预措施: regular dose of placebo (Drug)
placebo 2x regular dose group
干预措施: 2x regular dose of placebo (Drug)
regular dose group of Prunella oral liquid group
干预措施: regular dose of JiRui® Prunella oral liquid (Drug)
2x regular dose group of Prunella oral liquid group
干预措施: 2x regular dose of JiRui® Prunella oral liquid (Drug)
结局指标
主要结局
Rate of change in thyroid nodule volume from baseline at 9 months of treatment.
时间窗: 270 ± 14 days
次要结局
- Proportion of patients with reduced thyroid nodule volume from baseline at 12 months of treatment.(360 ± 14 days)
- Proportion of patients with reduced thyroid nodule volume ≥50% from baseline at 3 months of treatment.(90 ± 7 days)
- Proportion of patients with reduced thyroid nodule volume ≥50% from baseline at 9 months of treatment.(270 ± 14 days)
- Proportion of patients with reduced thyroid nodule volume ≥50% from baseline at 12 months of treatment.(360 ± 14 days)
- Rate of change in thyroid nodule volume from baseline at 3 months of treatment.(90 ± 7 days.)
- Rate of change in thyroid nodule volume from baseline at 12 months of treatment.(360 ± 14 days.)
- The change value of the maximum diameter of thyroid nodules from baseline at 3 months of treatment.(90 ± 7 days)
- The change value of the maximum diameter of thyroid nodules from baseline at 6 months of treatment.(180 ± 10 days)
- The change value of the maximum diameter of thyroid nodules from baseline at 9 months of treatment.(270 ± 14 days)
- The change value of the maximum diameter of thyroid nodules from baseline at 12 months of treatment.(360 ± 14 days)
- Proportion of patients with reduced thyroid nodule volume from baseline at 3 months of treatment.(90 ± 7 days)
- Proportion of patients with reduced thyroid nodule volume from baseline at 6 months of treatment.(180 ± 10 days)
- Proportion of patients with reduced thyroid nodule volume from baseline at 9 months of treatment.(270 ± 14 days)
- The proportion of patients with reduced thyroid nodule volume ≥50% from baseline at 6 months of treatment.(180 ± 10 days)
- Changes in the number of thyroid nodules from baseline at the 3 months of treatment.(90 ± 7 days)
- Changes in Tg, TgAb and TPOAb levels from baseline at the 6th month of treatment.(180 ± 10 days)
- Changes in the number of thyroid nodules from baseline at the 6 months of treatment.(180 ± 10 days)
- Changes in the number of thyroid nodules from baseline at the 9 months of treatment.(270 ± 14 days)
- Changes in serum TSH, FT3 and FT4 from baseline at the months of treatment.(180 ± 10 days)
- 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.(90 ± 7 days)
- 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.(180 ± 10 days)
- Rate of change in thyroid volume from baseline at 6 months of treatment.(180 ± 10 days)
- Changes in serum TSH, FT3 and FT4 from baseline at 9 months of treatment.(270 ± 14 days)
- Rate of change in thyroid volume from baseline at 12 months of treatment.(360 ± 14 days)
- Changes in the number of thyroid nodules from baseline at the 12 months of treatment.(360 ± 14 days)
- 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.(270 ± 14 days)
- 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.(360 ± 14 days)
- Subjects' quality of life scores (SF-36) at 6 months of treatment.(180 ± 10 days)
- Subjects' quality of life scores (SF-36) at 9 months of treatment.(270 ± 14 days)
- Rate of change in thyroid volume from baseline at 3 months of treatment.(90 ± 7 days)
- Rate of change in thyroid volume from baseline at 9 months of treatment.(270 ± 14 days)
- Changes in serum TSH, FT3 and FT4 from baseline at 12 months of treatment.(360 ± 14 days)
- Proportion of patients with normal thyroid function at 3 months of treatment.(90 ± 7 days)
- Proportion of patients with normal thyroid function at 6 months of treatment.(180 ± 10 days)
- Proportion of patients with normal thyroid function at 9 months of treatment.(270 ± 14 days)
- Proportion of patients with normal thyroid function at 12 months of treatment.(360 ± 14 days)
- Subjects' quality of life scores (SF-36) at 3 months of treatment.(90 ± 7 days)
- Subjects' quality of life scores (SF-36) at 12 months of treatment.(360 ± 14 days)
- Rate of change in thyroid nodule volume from baseline at 6 months of treatment.(180 ± 10 days.)
- Changes in serum TSH, FT3 and FT4 from baseline at the months of treatment.(90 ± 7 days)