The Efficacy of YiQiFuMai Injection as an Adjunctive Treatment for Sepsis

Evaluation of Efficacy of YiQiFuMai Injection as an Adjunctive Treatment for Sepsis: a Single Center Randomized Controlled Pilot Study

This is a prospective single center pilot randomized controlled study to assess the efficacy and safety of YiQiFuMai injection (YQFM), a widely used Chinese medicine, as an adjunctive treatment for sepsis.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis
• Intervention / Treatment: Drug: YiQiFuMai; Drug: 0.9% Normal Saline 250ml

Detailed Description

Sepsis is a major clinical challenge with high mortality and morbidity worldwide. Sepsis is characterized by the dysregulated host response to an infection followed by organ dysfunction. Early sepsis mortality has diminished with advances in intensive care management and goal-directed interventions, only to surge after "recovery" from acute events, which prompts a search for sepsis-induced alterations in immune function. When suffered from sepsis, patients may have evidence of hyper-inflammation and immunosuppression. There are no high-quality evidence examining the effect of intravenous (IV) immunoglobulins or other immune modulators on the outcomes of patients with sepsis or septic shock. YiQiFuMai Injection (YQFM) is a redeveloped preparation based on the traditional Chinese medicine formula Sheng-Mai-San, which is widely used in clinical practice in China, mainly for the microcirculatory disturbance-related diseases. YQFM is proved to be effective for treating sepsis (unpublished data). And several researches reveal that YQFM attenuates acute respiratory distress syndrome and lipopolysaccharide-induced microvascular disturbance in vitro.

The purpose of this study is to explore the adjunctive treatment effect of YQFM to prognosis, immune dysfunction and organ dysfunction of sepsis.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: An-lu Wang; Phone Number: +8662835151; Email: wwanganlu@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Sepsis defined by Sepsis-3 definition
• Adult patients between the ages of 18 and 90.
• Informed consent is provided by patients or obtained by family member if patient is incapacitated.

Exclusion Criteria:

• Known severe allergic reaction to drugs including but not limited to YQFM.
• Pregnant patients or those who may be pregnant
• Patients with severe intracranial diseases (intracranial artery stenosis, intracranial infection, cerebral hemorrhage, cerebral infarction, brain trauma, subjects after intracranial surgery)
• Patients with extremely severe brain injury, after cardiopulmonary resuscitation, advanced malignant tumor, combined with serious primary diseases such as liver, lung, kidney and hematopoietic system, and poor prognosis;
• Autoimmune diseases, immune deficiency diseases, continuous use of immunosuppressants within the last 6 months, or organ transplants;
• Major surgery or trauma within the last 2 weeks;
• Participated in other clinical trials or took similar drugs within 1 month;
• The investigator considered that the subjects had poor compliance or other clinical, social, or family factors that were inappropriate for inclusion in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YQFM group; YQFM 5.2g in 0.9% Normal Saline 250ml IV, about 40 drops per min, once a day.	Drug: YiQiFuMai; YQFM is a redeveloped preparation based on the traditional Chinese medicine formula Sheng-Mai-San, which is widely used in clinical practice in China, mainly for the microcirculatory disturbance-related diseases.
Placebo Comparator: Placebo group; 0.9% Normal Saline 250ml IV, about 40 drops per min.	Drug: 0.9% Normal Saline 250ml; 0.9% Normal Saline 250ml IV, about 40 drops per min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause Mortality [28 days after randomization]	Death from all causes at 28-days	In 28 days after randomization
Mortality in ICU and several time points	Death from all causes at ICU discharge, 7 days, and 14 days after randomization	In 14 days after randomization
The secondary infection rate in 28 days.		In 28 days after randomization
Length of stay in ICU		up to 28 days after randomization
Absolute lymphocyte count in the routine blood test (*10^9g/L)		Change from baseline at 14 days after randomization
Concentration of T cells and B cells	CD3+CD4-CD8-, CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4+CD8+, CD3+CD19-, CD3-CD19+, CD3+(CD16+CD56)+, CD3-(CD16+CD56)+ ,CD4+CD25+,CD4+CD25+CD127- (cells/uL)	Change from baseline at 14 days after randomization
Concentration of inflammatory cytokines	interleukin (IL) 1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, interferon (IFN) α, IFN-γ, and Tumor nuclear factor (TNF)-α. (pg/mL);	Change from baseline at 14 days after randomization
Concentration of Procalcitonin		Change from baseline at 14 days after randomization
Length of stay in hospital		up to 28 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of mechanical ventilation (MV) in ICU		up to 28 days after randomization
Duration of continual renal replacement therapy (CRRT) in ICU		up to 28 days after randomization
Duration of vasopressor drugs in ICU		up to 28 days after randomization
Duration of fluid resuscitation in ICU		up to 28 days after randomization
Total amount of fluid resuscitation (mL) in ICU		up to 28 days after randomization
SOFA score	Total Sequential Organ Failure Assessment (SOFA) score (0-24), higher values represent a worse outcome	Change from baseline at 14 days after randomization
APACHEII	Acute Physiology and Chronic Health Evaluation (include Acute physiology score, APS and age and Chronic physiology score, totally 0-71 Points)	change from baseline at 7 days after randomization
Self-Rating Anxiety Scale (SAS) score	Score range from 0 to 80, higher values represent a worse outcome	change from baseline at 28 days after randomization
Self-Rating Depression Scale (SDS) score	Score range from 0 to 80, higher values represent a worse outcome	change from Day 7 at 28 days after randomization
Barthel score	Score range from 0 to 100, higher values represent a better outcome	change from baseline at 28 days after randomization
The mean artery pressure (MBP)		change from baseline at 7 days after randomization
The worst heart rate		change from baseline at 7 days after randomization
Concentration of serum lactate		change from baseline at 14 days after randomization
The rate of lactate clearance	(baseline lactate-lactate)/baseline lactate	change from baseline at 14 days after randomization
The volume of urine output		change from baseline at 14 days after randomization
Concentration of IgM, IgG, IgE (g/L) (blood)		change from baseline at 14 days after randomization
Concentration of complement in serum (C3 and C4) (g/L)		change from baseline at 14 days after randomization

Collaborators and Investigators

• Sponsor: Xiyuan Hospital of China Academy of Chinese Medical Sciences
• Investigators: Principal Investigator: Zhixu Yang, Prof., Xiyuan Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): February 28, 2022
• Primary Completion (Anticipated): January 31, 2024
• Study Completion (Anticipated): October 31, 2024

Study Registration Dates

• First Submitted: December 26, 2021
• First Submitted That Met QC Criteria: February 22, 2022
• First Posted (Actual): March 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 3, 2022
• Last Update Submitted That Met QC Criteria: February 22, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: CI2021A02908

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No