Clinical Research on Shenfu Injection in Septic Patients

Study Overview
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Brief Summary
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Sepsis, characterized by organ dysfunction caused by infection, exhibits increasing incidence and mortality rates, posing a significant challenge to intensive care units. Early-stage sepsis involves hemodynamic disturbances, and severe and complex microcirculatory impairments can result in tissue hypoxia and accelerate organ dysfunction. Modern medical research has indicated that the effective and rapid restoration of microcirculatory function, along with the correction of microcirculatory disorders, is a crucial aspect in the treatment of sepsis. Current guidelines recommend the use of vasoactive drugs to address hemodynamic disturbances, but their administration may further damage the microcirculation. Additionally, in patients with severe sepsis, there often exists a disparity between macrocirculatory and microcirculatory hemodynamics, and conventional clinical indicators fail to directly reflect the level of microcirculatory perfusion. Chinese guidelines have incorporated the use of traditional Chinese medicine (TCM) in the diagnosis and treatment of sepsis, offering a new therapeutic approach to ameliorate microcirculatory impairments. This study aims to include patients with sepsis and administer Shenfu Injection via intravenous therapy. Tongue microcirculation assessment will be employed to evaluate changes in microvascular health scores, while transcutaneous oxygen and carbon dioxide pressure alterations, as well as serum lactate level variations, will be monitored to ascertain the effects of Shenfu Injection on improving early-stage microcirculatory impairments and microvascular leakage in sepsis patients. This research will clarify the clinical efficacy of Shenfu Injection in sepsis patients with microcirculatory impairments, provide evidence-based medicine and clinical evidence for TCM treatment of sepsis, and offer a solid foundation for refining sepsis treatment strategies with distinct Chinese characteristics.

Official Title
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Improving Microcirculation and Microvascular Leakage in Sepsis Patients: A Comprehensive Clinical Study of Shenfu Injection

Conditions
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Sepsis

Intervention / Treatment
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* Drug: Shen-Fu
* Drug: Norepinephrine (NE)，antibiotics，fluid resuscitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years; Signed informed consent form; Meets sepsis 3.0 diagnostic criteria; Exclusion Criteria: Age < 18 years; Known pregnancy; Inability to accept and complete signed informed consent within 24 hours of diagnosis of sepsis; Status of tracheal intubation; oral mucosal inflammation or damage; Patients with contraindications to transcutaneous oxygen partial pressure testing such as severe edema and burns; Concurrent participation in other treatment studies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Shenfu Injection group<br>within 24 hours after the diagnosis of sepsis, Shenfu injection 100 ml/day, intravenous use, continuous application for 7 days. | Drug: Shen-Fu<br>* Within 24 hours of sepsis diagnosis, patients received a daily intravenous infusion of 100 ml of Shenfu Injection for a continuous duration of 7 days.<br>* Other names: Traditional Chinese medicine;|
| Placebo Comparator: Control group<br>sepsis was treated with standardized western medicine methods | Drug: Norepinephrine (NE)，antibiotics，fluid resuscitation<br>* empirical antimicrobial treatment (which is promptly administered after microbial tests), fluid (crystalloids) replacement (to be established according to fluid tolerance and fluid responsiveness), and vasoactive agents (e.g., norepinephrine (NE)), which are employed to maintain mean arterial pressure above 65 mmHg and reduce the risk of fluid overload<br>* Other names: Strandard treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HR:heart rate | heart rate | Day0，Day1，Day 3，Day 7 | 
| BP:Blood pressure | Blood pressure | Day0，Day1，Day 3，Day 7 | 
| Proportion of perfused vessels | Grid-based score (3 horizontal and vertical equidistant lines). Percentage of perfused vessels per total number of vessel crossings | Day0，Day1，Day 3，Day 7 | 
| Microvascular fow index | fow, 1 = intermittent fow, 2 = sluggish fow, 3 = normal fow Semi-quantitative assessment of the average red blood cell velocity per quadrant | Day0，Day1，Day 3，Day 7 | 
| Heterogeneity index | Determinant of heterogeneity of blood fow, characteristic of distributive abnormalities | Day0，Day1，Day 3，Day 7 | 
| Hemodynamic parameters1 | CI: Cardio index | Day0，Day1，Day 3，Day 7 | 
| Hemodynamic parameters2 | SVRI:systemic vascular resistance index | Day0，Day1，Day 3，Day 7 | 
| Hemodynamic parameters3 | GEDVI:global end-diastolic volume index | Day0，Day1，Day 3，Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ang2:Endothelial cell function indicators | Endothelial cell function indicators got from the blood of patients | Day0，Day1，Day 3，Day 7 | 
| VCAM1:Endothelial cell function indicators | Endothelial cell function indicators got from the blood of patients | Day0，Day1，Day 3，Day 7 | 
| Sydecan-1:Endothelial cell function indicators | Endothelial cell function indicators got from the blood of patients | Day0，Day1，Day 3，Day 7 | 
| 6-Keto-PGF-1:Endothelial cell function indicators | Endothelial cell function indicators got from the blood of patients | Day0，Day1，Day 3，Day 7 | 
| TXB2:Endothelial cell function indicators | Endothelial cell function indicators got from the blood of patients | Day0，Day1，Day 3，Day 7 | 
| NO:Endothelial cell function indicators | Endothelial cell function indicators got from the blood of patients | Day0，Day1，Day 3，Day 7 | 
| Lab test1 | PH | Day0，Day1，Day 3，Day 7 | 
| Lab test2 | PaO2 mmHg, | Day0，Day1，Day 3，Day 7 | 
| Lab test3 | PaCO2 mmHg | Day0，Day1，Day 3，Day 7 | 
| Lab test4 | Serum lactate mmol/L | Day0，Day1，Day 3，Day 7 | 
| Lab test5 | IL-10 ng/ml | Day0，Day1，Day 3，Day 7 | 
| Lab test6 | WBC ×109/L | Day0，Day1，Day 3，Day 7 | 
| Lab test7 | Neu ×109/L | Day0，Day1，Day 3，Day 7 | 
| Lab test8 | Lym×109/L, | Day0，Day1，Day 3，Day 7 | 
| Lab test9 | Hb g/L, | Day0，Day1，Day 3，Day 7 | 
| Lab test10 | PLT×109/L | Day0，Day1，Day 3，Day 7 | 
| Lab test11 | Total bilirubin IU/L | Day0，Day1，Day 3，Day 7 | 
| Lab test12 | Cr μmol/L | Day0，Day1，Day 3，Day 7 | 
| Lab test13 | IL-1βng/ml | Day0，Day1，Day 3，Day 7 | 
| Lab test14 | APTT s | Day0，Day1，Day 3，Day 7 | 
| Lab test15 | D-Dimermg/L | Day0，Day1，Day 3，Day 7 | 
| Lab test16 | CRP mg/L | Day0，Day1，Day 3，Day 7 | 
| Lab test17 | ProBNP pg/ml | Day0，Day1，Day 3，Day 7 | 
| Lab test18 | PCT ng/ml | Day0，Day1，Day 3，Day 7 | 
| Lab test19 | TNFαng/ml | Day0，Day1，Day 3，Day 7 | 
| Lab test20 | IL-6 ng/ml | Day0，Day1，Day 3，Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sepsis, microcirculation, Shenfu Injection