Pharmacokinetics of XueBiJing in Patients With Sepsis

Sepsis Clinical Trial

Official title:

Pharmacokinetic Study of XueBiJing Injection in Patients With Sepsis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03475732
• Other study ID #: 2017ZDSYLL123-P01
• Status: Completed
• Phase: N/A
• Start date: March 18, 2018
• Est. completion date: December 31, 2019

Study information

• Verified date: January 2021
• Source: Southeast University, China
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Pharmacokinetics and disposition of XueBiJing compounds in patients with sepsis

Description:

XueBiJing injection, a five-herb combination approved by Chinese FDA in 2004, has been widely used as an add-on therapy in routine sepsis care in Chinese clinics. A comprehensive pharmacokinetic research on this herbal injection has been conducted in healthy human subjects, and the major circulating XueBiJing compounds, as well as their systemic exposure levels and forms and pharmacokinetic characteristics, have been identified. However, it is known that sepsis may induce hepatic, renal and cardiac dysfunction, alter drug metabolizing enzymes and transporters activities, increase capillary permeability, and induce various pathophysiological changes. All these will affect the concentrations at the action sites and pharmacokinetic characteristics of XueBiJing compounds, which contribute to the injection's overall therapeutic action, thus influencing the anti-septic efficacy of the injection. The purpose of this prospective, open label study is to identify the circulating XueBiJing compounds in patients with sepsis after intravenously dosing XueBiJing injection and their systemic exposure forms and levels, pharmacokinetic characteristics, and the associated inter-patient differences of these XueBiJing compounds.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: December 31, 2019
• Est. primary completion date: June 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 18= age =70 years old

• Community acquired pneumonia patients who met the Sepsis-3 criteria from Society of Critical Care Medicine (SCCM) /European Society of Intensive Care Medicine (ESICM) with2 =SOFA =13

• To use XueBiJing injection as an add-on therapy to treat sepsis decided byclinician

• Informed consent obtained

Exclusion Criteria:

• Diagnosis of sepsis for over 48 h

• Pregnant or lactating women

• Patients with a history of anaphylaxis or allergyto XueBiJing or its component herbs

• Patients participated in an investigational clinical trial within 30 days prior to this study

• Patients unable or unsuitable to participate in this study decided by the investigator (i.e., patients whose death are deemed within 48 h or who poorly adhere to the treatment)

Related Conditions & MeSH terms

• Community Acquired Pneumonia
• Pneumonia
• Sepsis
• Septic Shock
• Shock, Septic
• Toxemia

Intervention

Drug:
• XueBiJing injection
100mL XueBiJing injection (dissolved with 100 mL of 0.9% normal saline),intravenous infusion for 1.25 h, q12h for 5 days

Locations

Country	Name	City	State
China	Zhongda Hospital, Southeast University	Nanjing	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
Southeast University, China	Chinese Academy of Sciences

Country where clinical trial is conducted

China, 

References & Publications (7)

Blot SI, Pea F, Lipman J. The effect of pathophysiology on pharmacokinetics in the critically ill patient--concepts appraised by the example of antimicrobial agents. Adv Drug Deliv Rev. 2014 Nov 20;77:3-11. doi: 10.1016/j.addr.2014.07.006. Epub 2014 Jul 15. Review. — View Citation

Cheng C, Lin JZ, Li L, Yang JL, Jia WW, Huang YH, Du FF, Wang FQ, Li MJ, Li YF, Xu F, Zhang NT, Olaleye OE, Sun Y, Li J, Sun CH, Zhang GP, Li C. Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats. Acta Pharmacol Sin. 2016 Apr;37(4):530-44. doi: 10.1038/aps.2015.103. Epub 2016 Feb 1. — View Citation

Harvey RD, Morgan ET. Cancer, inflammation, and therapy: effects on cytochrome p450-mediated drug metabolism and implications for novel immunotherapeutic agents. Clin Pharmacol Ther. 2014 Oct;96(4):449-57. doi: 10.1038/clpt.2014.143. Epub 2014 Jul 2. Review. — View Citation

Li X, Cheng C, Wang F, Huang Y, Jia W, Olaleye OE, Li M, Li Y, Li C. Pharmacokinetics of catechols in human subjects intravenously receiving XueBiJing injection, an emerging antiseptic herbal medicine. Drug Metab Pharmacokinet. 2016 Feb;31(1):95-98. doi: 10.1016/j.dmpk.2015.10.005. Epub 2015 Nov 4. — View Citation

Li YP, Qiao YJ, Wu ZX, Yao YM, Yu Y, Wu Y. [Effects of Xuebijing injection on high-mobility group box chromosomal protein 1 in septic rats]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2007 Apr;19(4):239-41. Chinese. — 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

Sinnollareddy MG, Roberts MS, Lipman J, Roberts JA. ß-lactam pharmacokinetics and pharmacodynamics in critically ill patients and strategies for dose optimization: a structured review. Clin Exp Pharmacol Physiol. 2012 Jun;39(6):489-96. doi: 10.1111/j.1440-1681.2012.05715.x. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma concentrations of XueBiJing injection compounds	Plasma concentrations of XueBiJing injection compounds	On 1stand 5th day of giving XueBiJing injection: pre-dose, 1.25 h after starting the infusion, and 0.5, 1, 2, 4, and 8 h after terminating the infusion On 2nd to 4th day of giving XueBiJing injection: pre-dose and 1.25 h after starting the infusion
Secondary	Accumulative amounts of XueBiJing compounds in urine	Accumulative amounts of XueBiJing compounds in urine	On 1st day of giving XueBiJing injection: pre-dose and 0-3.25 and 3.25-12 h after starting the infusion On 5thday of giving XueBiJing injection:0-3.25 and 3.25-12 h after starting the infusion