Evidence-based Evaluation and Mechanism of Shenhuang Granules in the Treatment of Sepsis: a Randomized, Double-blind, Placebo-controlled, Effective Clinical Trial
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 410
- 试验地点
- 1
- 主要终点
- 28-day mortality rate
研究概览
简要总结
Sepsis is a life-threatening organ dysfunction caused by the body's dysfunctional response to infection, most patients require treatment in the ICU, and is the leading cause of death worldwide. Over the years, the development of new drugs for the treatment of sepsis has failed without significant benefit in reducing mortality, and there is currently no effective drug treatment. Therefore, sepsis is a serious disease threatening the life and health of patients, causing a huge burden to society, and is a major problem in the medical field.
The pathogenesis of sepsis is complicated, and immune imbalance is the key mechanism. Suppression of host immune function may be the root cause of the increase in the long-term mortality of sepsis. Bidirectional immune regulation may be an important treatment plan to improve the survival rate and quality of life of sepsis patients. In recent years, the contribution of traditional Chinese medicine to sepsis has been highly valued at home and abroad. The treatment of sepsis by traditional Chinese medicine mainly plays the role of bidirectional immune regulation by dispelling the evil and supporting the right. Our team has achieved some results in the diagnosis and treatment of sepsis by using traditional Chinese medicine. Supported by National Natural Science Foundation of China (81774070). The team also found that magnolol can inhibit intestinal mucosal inflammation in sepsis, which was also supported by the National Natural Science Foundation of China (82174178). The team of Qhuang scholars inherit the academic experience of Zhu Liangchun, the master of Chinese medicine, warm and hot disease need not be limited to the law of wei, qi, ying, blood transmission, that is, the disease can be solved both outside and inside, breaking the three bans of warm and cold disease. On the basis of inheriting Zhu Liangchun's academic theory, the author put forward the early treatment rule of "truncation and reversal", and used to cleanse the "poison" and "save Yin" in the early stage of sepsis to quickly truncate the malignant development trend of sepsis. In the COVID-19 epidemic, we have found that patients with COVID-19 sepsis have "acute deficiency syndrome" in the early stage of clinical syndrome, which is an important factor leading to death. The clinical efficacy and mechanism of "Shenhuang Granules" in sepsis caused by non-novel coronavirus infection such as bacteria need to be further studied.
详细描述
- Baseline data: patient's name, gender, age, enrollment diagnosis, sepsis diagnosis time, combined underlying disease, allergy history, personal history, body temperature, respiration, heart rate, blood pressure, blood oxygen saturation and other vital signs.
- Primary outcome measure: 28-day mortality
- Secondary outcome indicators:
A. Total length of stay and ICU stay B. Total hospitalization costs and ICU hospitalization costs C. Overall mortality and ICU mortality D.28 days cumulative no mechanical ventilation time E. Information of TCM syndrome such as tongue and pulse on day 0 and day 5-7 F. TCM symptom scores on days 0 and 5-7 G. SOFA score and APACHE II score on days 0 and 5-7. 4. Other observation indicators (day 0 and 7) :
A. Inflammatory markers: WBC, percentage of neutrophils, CRP, PCT, tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10); B. Main organ function indicators: BNP, TnI, creatinine, urea nitrogen, total bilirubin, direct bilirubin, indirect bilirubin, AST, ALT, arterial lactic acid; C. Coagulation indicators: PT, APTT; D. Immune function: absolute number of lymphocytes, number of CD4+T cells, number of CD8+T cells, number of B cells, number of NK cells. 5. Safety indicators: adverse reaction symptoms or adverse events (such as allergies).
If you need to collect stool and blood samples, you also need to observe the following indicators, if not, please ignore. 6. Metabolomic study: Serum samples from day 0 and day 5-7 were collected for the study of the main functional components of Shenhuang granules and metabolomic analysis; 7. Intestinal microecology study: Stool samples from day 0 and day 5-7 were collected for intestinal microecology study.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This study will adopt the block randomization method to randomly assign qualified subjects to the test group or the control group in a ratio of 1:1. A central randomization system was used for randomization and drug distribution management. From randomization until the database is locked, subjects, investigators, data analysts, sponsors, and all medical personnel involved in the treatment or clinical evaluation will remain blind to the reality of the treatment.
The random number table (blind bottom) used in this study will be generated by the randomization specialist and imported into the system. The random number is reproducible. The relationship between the experimental group drug or the control group simulated drug and the subjects was represented by random number and drug number. The blind bottom is kept by the randomisation Specialist and remains unknown to both subjects and investigators throughout the trial.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years old
- •Meet the diagnostic criteria of sepsis 3.0 guidelines
- •Sign informed consent.
排除标准
- •Liver or kidney single SOFA score ≥3 points of liver and kidney dysfunction
- •Death is expected within 48 hours, or SOFA≥15 points, or APACHE II ≥30 points, or the patient refuses active treatment
- •Patients with allergic reactions to traditional Chinese medicine
- •Patients treated with chemotherapy or radiotherapy or high-dose immunosuppressants within the last 1 month
- •Participants in other clinical trials at the same time or within 30 days
- •Pregnant and lactating women
- •Patients with severe gastrointestinal bleeding, intestinal obstruction, or severe intraperitoneal pressure elevation (IAP≥20mmHg).
研究组 & 干预措施
Treatment group
Sepsis cluster therapy + Shenhuang granules for 5 days. For the treatment of sepsis cluster, refer to the 2021 International Guidelines for Severe Sepsis and Septic Shock. Shenhuang Granules (Tianjin Hongri Pharmaceutical Co., LTD.) : 2 times a day, 1 pack each time, 100ml of warm water (temperature about 40°C) after dissolution, oral or nasal feeding (stomach tube or intestinal tube).
干预措施: shenhuang granule (Drug)
Control group
Sepsis cluster therapy + placebo for 5 days. For the treatment of sepsis cluster, refer to the 2021 International Guidelines for Severe Sepsis and Septic Shock. Placebo (Tianjin Hongri Pharmaceutical Co., LTD.) : After dissolution of 100ml warm water (temperature about 40°C) in 1 pack twice a day, oral or nasal feeding (gastric tube or intestinal tube).
干预措施: placebo (Drug)
结局指标
主要结局
28-day mortality rate
时间窗: 28-day
The proportion of deaths due to illness within 28 days after treatment began
次要结局
- Total length of stay and ICU stay(7 day after treatment，14 day after treatment，28 day after treatment)
- Total hospitalization costs and ICU hospitalization costs(7 day after treatment，14 day after treatment，28 day after treatment)
- Overall mortality and ICU mortality(7 day after treatment，14 day after treatment，28 day after treatment)
- 28 days cumulative no mechanical ventilation time(28 day after treatment)
- SOFA score(day 0，day 5-7)
- APACHE II score(day 0，day 5-7)