Clinical Research on Shenfu Injection in Septic Patients

Sepsis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06157320
• Other study ID #: 320.6750.2022-2-35
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2023
• Est. completion date: January 1, 2026

Study information

• Verified date: January 2023
• Source: Ruijin Hospital
• Contact: Hongping Qu, phD,MD
• Phone: +86 13641801889
• Email: hongpingqu0412[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 1, 2026
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Sepsis

Intervention

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.
• 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

Locations

Country	Name	City	State
China	Ruijin Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Ruijin Hospital	Wu Jieping Medical Foundation

Country where clinical trial is conducted

China, 

References & Publications (10)

Fan KL, Wang JH, Kong L, Zhang FH, Hao H, Zhao H, Tian ZY, Yin MX, Fang H, Yang HH, Liu Y. Effect of Shen-Fu Injection () on Hemodynamics in Early Volume Resuscitation Treated Septic Shock Patients. Chin J Integr Med. 2019 Jan;25(1):59-63. doi: 10.1007/s1 — View Citation

Gutterman DD, Chabowski DS, Kadlec AO, Durand MJ, Freed JK, Ait-Aissa K, Beyer AM. The Human Microcirculation: Regulation of Flow and Beyond. Circ Res. 2016 Jan 8;118(1):157-72. doi: 10.1161/CIRCRESAHA.115.305364. — View Citation

Ince C. Hemodynamic coherence and the rationale for monitoring the microcirculation. Crit Care. 2015;19 Suppl 3(Suppl 3):S8. doi: 10.1186/cc14726. Epub 2015 Dec 18. — View Citation

Otero RM, Nguyen HB, Huang DT, Gaieski DF, Goyal M, Gunnerson KJ, Trzeciak S, Sherwin R, Holthaus CV, Osborn T, Rivers EP. Early goal-directed therapy in severe sepsis and septic shock revisited: concepts, controversies, and contemporary findings. Chest. — View Citation

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287. — View Citation

Tian R, Li R, Liu Y, Liu J, Pan T, Zhang R, Liu B, Chen E, Tang Y, Qu H. Metformin ameliorates endotoxemia-induced endothelial pro-inflammatory responses via AMPK-dependent mediation of HDAC5 and KLF2. Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6 — View Citation

Tian R, Wang X, Pan T, Li R, Wang J, Liu Z, Chen E, Mao E, Tan R, Chen Y, Liu J, Qu H. Plasma PTX3, MCP1 and Ang2 are early biomarkers to evaluate the severity of sepsis and septic shock. Scand J Immunol. 2019 Dec;90(6):e12823. doi: 10.1111/sji.12823. Epu — View Citation

Yao B, Liu DW, Chai WZ, Wang XT, Zhang HM. Microcirculation dysfunction in endotoxic shock rabbits is associated with impaired S-nitrosohemoglobin-mediated nitric oxide release from red blood cells: a preliminary study. Intensive Care Med Exp. 2019 Jan 7; — View Citation

Zhang X, Guo T, Zhang K, Guo W, An X, Gao P. Effect of shenfu injection on microcirculation in shock patients: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2020 Oct 23;99(43):e22872. doi: 10.1097/MD.0000000000022872. — View Citation

Zhang XJ, Song L, Zhou ZG, Wang XM. Effect of shenfu injection on gastrointestinal microcirculation in rabbits after myocardial ischemia-reperfusion injury. World J Gastroenterol. 2006 Jul 21;12(27):4389-91. doi: 10.3748/wjg.v12.i27.4389. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HR:heart rate	heart rate	Day0,Day1,Day 3,Day 7
Primary	BP:Blood pressure	Blood pressure	Day0,Day1,Day 3,Day 7
Primary	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
Primary	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
Primary	Heterogeneity index	Determinant of heterogeneity of blood fow, characteristic of distributive abnormalities	Day0,Day1,Day 3,Day 7
Primary	Hemodynamic parameters1	CI: Cardio index	Day0,Day1,Day 3,Day 7
Primary	Hemodynamic parameters2	SVRI:systemic vascular resistance index	Day0,Day1,Day 3,Day 7
Primary	Hemodynamic parameters3	GEDVI:global end-diastolic volume index	Day0,Day1,Day 3,Day 7
Secondary	Ang2:Endothelial cell function indicators	Endothelial cell function indicators got from the blood of patients	Day0,Day1,Day 3,Day 7
Secondary	VCAM1:Endothelial cell function indicators	Endothelial cell function indicators got from the blood of patients	Day0,Day1,Day 3,Day 7
Secondary	Sydecan-1:Endothelial cell function indicators	Endothelial cell function indicators got from the blood of patients	Day0,Day1,Day 3,Day 7
Secondary	6-Keto-PGF-1:Endothelial cell function indicators	Endothelial cell function indicators got from the blood of patients	Day0,Day1,Day 3,Day 7
Secondary	TXB2:Endothelial cell function indicators	Endothelial cell function indicators got from the blood of patients	Day0,Day1,Day 3,Day 7
Secondary	NO:Endothelial cell function indicators	Endothelial cell function indicators got from the blood of patients	Day0,Day1,Day 3,Day 7
Secondary	Lab test1	PH	Day0,Day1,Day 3,Day 7
Secondary	Lab test2	PaO2 mmHg,	Day0,Day1,Day 3,Day 7
Secondary	Lab test3	PaCO2 mmHg	Day0,Day1,Day 3,Day 7
Secondary	Lab test4	Serum lactate mmol/L	Day0,Day1,Day 3,Day 7
Secondary	Lab test5	IL-10 ng/ml	Day0,Day1,Day 3,Day 7
Secondary	Lab test6	WBC ×109/L	Day0,Day1,Day 3,Day 7
Secondary	Lab test7	Neu ×109/L	Day0,Day1,Day 3,Day 7
Secondary	Lab test8	Lym×109/L,	Day0,Day1,Day 3,Day 7
Secondary	Lab test9	Hb g/L,	Day0,Day1,Day 3,Day 7
Secondary	Lab test10	PLT×109/L	Day0,Day1,Day 3,Day 7
Secondary	Lab test11	Total bilirubin IU/L	Day0,Day1,Day 3,Day 7
Secondary	Lab test12	Cr µmol/L	Day0,Day1,Day 3,Day 7
Secondary	Lab test13	IL-1ßng/ml	Day0,Day1,Day 3,Day 7
Secondary	Lab test14	APTT s	Day0,Day1,Day 3,Day 7
Secondary	Lab test15	D-Dimermg/L	Day0,Day1,Day 3,Day 7
Secondary	Lab test16	CRP mg/L	Day0,Day1,Day 3,Day 7
Secondary	Lab test17	ProBNP pg/ml	Day0,Day1,Day 3,Day 7
Secondary	Lab test18	PCT ng/ml	Day0,Day1,Day 3,Day 7
Secondary	Lab test19	TNFang/ml	Day0,Day1,Day 3,Day 7
Secondary	Lab test20	IL-6 ng/ml	Day0,Day1,Day 3,Day 7