Clinical Research on Shenfu Injection in Septic Patients

Sponsor

Ruijin Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT06157320

Collaborator

Wu Jieping Medical Foundation (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Sepsis	Drug: Shen-Fu Drug: Norepinephrine (NE)，antibiotics，fluid resuscitation	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Jan 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Shenfu Injection group within 24 hours after the diagnosis of sepsis, Shenfu injection 100 ml/day, intravenous use, continuous application for 7 days.	Drug: Shen-Fu 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. Other Names: Traditional Chinese medicine
Placebo Comparator: Control group sepsis was treated with standardized western medicine methods	Drug: Norepinephrine (NE)，antibiotics，fluid resuscitation 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 Other Names: Strandard treatment

Arm

Intervention/Treatment

Experimental: Shenfu Injection group

within 24 hours after the diagnosis of sepsis, Shenfu injection 100 ml/day, intravenous use, continuous application for 7 days.

Drug: Shen-Fu

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.

Other Names:

Traditional Chinese medicine

Placebo Comparator: Control group

sepsis was treated with standardized western medicine methods

Drug: Norepinephrine (NE)，antibiotics，fluid resuscitation

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

Other Names:

Strandard treatment

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.