Clinical Research on Shenfu Injection in Septic Patients

NCT06157320 | Unknown

• 1 other identifier: 320.6750.2022-2-35
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis

Keywords

sepsis; microcirculation; Shenfu Injection

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (26)

• Ang2:Endothelial cell function indicators

  Day0，Day1，Day 3，Day 7

• VCAM1:Endothelial cell function indicators

  Day0，Day1，Day 3，Day 7

• Sydecan-1:Endothelial cell function indicators

  Day0，Day1，Day 3，Day 7

• 6-Keto-PGF-1:Endothelial cell function indicators

  Day0，Day1，Day 3，Day 7

• TXB2:Endothelial cell function indicators

  Day0，Day1，Day 3，Day 7

Study Arms (2)

Shenfu Injection group

EXPERIMENTAL

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

Drug: Shen-Fu

Control group

PLACEBO COMPARATOR

sepsis was treated with standardized western medicine methods

Drug: Norepinephrine (NE)，antibiotics，fluid resuscitation

Interventions

Shen-Fu DRUG

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.

Also known as: Traditional Chinese medicine

Shenfu Injection group

Norepinephrine (NE)，antibiotics，fluid resuscitation DRUG

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

Also known as: Strandard treatment

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years;
• Signed informed consent form;
• Meets sepsis 3.0 diagnostic criteria;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ruijin Hospital: lead
• Wu Jieping Medical Foundation: collaborator

Study Sites (1)

Ruijin Hospital

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

Related Publications (10)

• 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.

  PMID: 26903338 BACKGROUND

• 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.

  PMID: 26837746 RESULT

• 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. Epub 2019 Oct 7.

  PMID: 31489646 RESULT

• 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):1701-1712. doi: 10.1016/j.bbadis.2019.04.009. Epub 2019 Apr 16.

  PMID: 31002870 RESULT

• 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;7(1):1. doi: 10.1186/s40635-018-0215-0.

  PMID: 30617929 RESULT

• 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. 2006 Nov;130(5):1579-95. doi: 10.1378/chest.130.5.1579.

  PMID: 17099041 RESULT

• 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/s11655-017-2965-z. Epub 2017 Oct 6.

  PMID: 28986814 RESULT

• 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.

  PMID: 16865783 RESULT

• 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.

  PMID: 33120828 RESULT

• 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.

  PMID: 26729241 RESULT

MeSH Terms

Conditions

Sepsis

Interventions

Shen-Fu; Medicine, Chinese Traditional; Norepinephrine

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Medicine, East Asian Traditional; Medicine, Traditional; Complementary Therapies; Therapeutics; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Hongping Qu

  Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital

  STUDY DIRECTOR

Central Study Contacts

Hongping Qu, phD，MD

CONTACT

+86 13641801889; hongpingqu0412@hotmail.com

Hongping Qu, phD,MD

CONTACT

+86 13641801889; hongpingqu0412@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2023
• First Posted: December 5, 2023
• Study Start: December 1, 2023
• Primary Completion: September 1, 2025
• Study Completion: January 1, 2026
• Last Updated: December 5, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)