Clinical trial NCT06514339: Evidence-based Evaluation and Mechanism of Shenhuang Granules in the Treatment of Sepsis
Official title: Evidence-based Evaluation and Mechanism of Shenhuang Granules in the Treatment of Sepsis: a Randomized, Double-blind, Placebo-controlled, Effective Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Sepsis
Keywords: Sepsis
Shenhuang granules
Evidence-based evaluation
Effect mechanism research
Lead sponsor: The First Affiliated Hospital of Zhejiang Chinese Medical University
Sponsor class: OTHER
Collaborators: name: Zhejiang University
name: Red Cross Hospital, Hangzhou, China
name: Ningbo Hospital of Traditional Chinese Medicine
First posted: 2024-07-23
Enrollment: 410
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The researchers were randomly assigned to either a trial or a control group. Experimental group: sepsis cluster therapy + Shenhuang granules, course of 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).

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).
Primary purpose: TREATMENT

Brief 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.

Detailed description: 1. 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.
2. Primary outcome measure: 28-day mortality
3. 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.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 years old
* Meet the diagnostic criteria of sepsis 3.0 guidelines
* Sign informed consent.

Exclusion Criteria:

* 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).

Primary outcomes:
measure: 28-day mortality rate
timeFrame: 28-day
Secondary outcomes:
measure: Total length of stay and ICU stay
timeFrame: 7 day after treatment，14 day after treatment，28 day after treatment
measure: Total hospitalization costs and ICU hospitalization costs
timeFrame: 7 day after treatment，14 day after treatment，28 day after treatment
measure: Overall mortality and ICU mortality
timeFrame: 7 day after treatment，14 day after treatment，28 day after treatment
measure: 28 days cumulative no mechanical ventilation time
timeFrame: 28 day after treatment
measure: SOFA score
timeFrame: day 0，day 5-7
measure: APACHE II score
timeFrame: day 0，day 5-7
Other outcomes:
measure: Blood routine test
timeFrame: day 0，7 day after treatment
measure: C-reactive protein
timeFrame: day 0，7 day after treatment
measure: Procalcitonin
timeFrame: day 0，7 day after treatment
measure: TNF-α
timeFrame: day 0，7 day after treatment
measure: interleukin-6 (IL-6), interleukin-10 (IL-10)
timeFrame: day 0，7 day after treatment
measure: Routine biochemical tests
timeFrame: day 0，7 day after treatment
measure: Arterial lactic acid
timeFrame: day 0，7 day after treatment
measure: Thrombin time
timeFrame: day 0，7 day after treatment
measure: Partial activated thromboplastin time
timeFrame: day 0，7 day after treatment
measure: Immune function
timeFrame: day 0，7 day after treatment
measure: Adverse event table
timeFrame: Day 0，7 day after treatment，14 day after treatment，28 day after treatment
measure: Changes in bile acid profile composition
timeFrame: Day 0, day 5-7
Locations:
city: Hangzhou
country: China
facility: First Affiliated Hospital of Zhejiang Chinese Medical University
state: Zhejiang
Study officials:
affiliation: The First Affiliated Hospital of Zhejiang Chinese Medical University
name: Wu JianNong, doctor
role: STUDY_CHAIR
affiliation: The First Affiliated Hospital of Zhejiang Chinese Medical University
name: Liu ShanShan, doctor
role: STUDY_DIRECTOR
affiliation: The First Affiliated Hospital of Zhejiang Chinese Medical University
name: Feng DanDan, master
role: STUDY_DIRECTOR
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