Evidence-based Evaluation and Mechanism of Shenhuang Granules in the Treatment of Sepsis
NCT Number: NCT06514339
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: EARLY_PHASE1
Conditions: Sepsis
Interventions: DRUG: shenhuang granule|DRUG: placebo
Sponsor: The First Affiliated Hospital of Zhejiang Chinese Medical University
Collaborators: Zhejiang University|Red Cross Hospital, Hangzhou, China|Ningbo Hospital of Traditional Chinese Medicine
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 410
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-09-01
Completion Date: 2026-07-01
Locations: First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310006, China

Summary:
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.

Primary Outcome Measures: 28-day mortality rate, The proportion of deaths due to illness within 28 days after treatment began, 28-day
Secondary Outcome Measures: Total length of stay and ICU stay, Total length of stay and length of stay in ICU, 7 day after treatment，14 day after treatment，28 day after treatment|Total hospitalization costs and ICU hospitalization costs, The patient's total hospitalization costs and hospitalization costs in the ICU, 7 day after treatment，14 day after treatment，28 day after treatment|Overall mortality and ICU mortality, The proportion of patients who died during their total hospital stay and the proportion of patients who died during their ICU stay were included, 7 day after treatment，14 day after treatment，28 day after treatment|28 days cumulative no mechanical ventilation time, The total time the patient spent without mechanical ventilation (such as a ventilator) in the 28 days following the start of treatment., 28 day after treatment|SOFA score, The SOFA score uses six criteria to reflect the function of organ systems (respiratory, blood, liver, cardiovascular, nervous, and kidney) and sets each on a score of 0-4. The objective was to describe the occurrence, development and incidence of MODS, day 0，day 5-7|APACHE II score, The APACHE II score is based on 12 physiological indicators, age, and health status on a scale of 0-71. The higher the score, the more severe the reaction condition, the worse the prognosis, and the higher the expected fatality rate, day 0，day 5-7
Other Outcome Measures: Blood routine test, It mainly includes WBC, percentage of neutrophils，The percentages of white blood cells and neutrophils represent inflammation, with higher values indicating higher inflammation., day 0，7 day after treatment|C-reactive protein, C-reactive protein on behalf of the inflammation, the higher the value, the higher the inflammatory conditions., day 0，7 day after treatment|Procalcitonin, Procalcitonin, the degree of its increase is positively correlated with the degree of infection. Used in the identification of bacteria and viruses, to monitor the severity of the infection, is used to evaluate the therapeutic effect and prognosis of infection., day 0，7 day after treatment|TNF-α, It is one of the cytokines involved in the inflammatory response and is used to evaluate the therapeutic effect and prognosis of infection., day 0，7 day after treatment|interleukin-6 (IL-6), interleukin-10 (IL-10), It is one of the cytokines involved in the inflammatory response and is used to evaluate the therapeutic effect and prognosis of infection., day 0，7 day after treatment|Routine biochemical tests, Among them, abnormal total bilirubin, direct bilirubin, indirect bilirubin, AST, and ALT indicated liver function problems, abnormal BNP and TnI indicated heart function problems, and abnormal creatinine and urea nitrogen indicated renal function problems, day 0，7 day after treatment|Arterial lactic acid, Arterial lactate was significantly associated with inflammation. Inflammatory reaction period, memory increased plasma lactate levels, lactic acid leels may aggravate the inflammatory response at the same time, day 0，7 day after treatment|Thrombin time, Its numerical and coagulation index significantly correlated, prothrombin time is screening test of the extrinsic coagulation pathway., day 0，7 day after treatment|Partial activated thromboplastin time, Its value is significantly correlated with coagulation indexes, and it is the most sensitive and commonly used screening test for endogenous coagulation system., day 0，7 day after treatment|Immune function, It mainly includes the absolute number of lymphocytes, the number of CD4+T cells, the number of CD8+T cells, the number of B cells, the number of NK cells and other indicators to evaluate the immune function of patients, day 0，7 day after treatment|Adverse event table, Patient safety during treatment was assessed by the Adverse Events Table, Day 0，7 day after treatment，14 day after treatment，28 day after treatment|Changes in bile acid profile composition, Blood samples were collected, and the changes in the number and concentration of bile acids in the blood were analyzed to explore the changes in the composition of the bile acid spectrum before and after treatment, Day 0, day 5-7