The Efficacy of YiQiFuMai Injection as an Adjunctive Treatment for Sepsis

Study Overview
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Brief Summary
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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.

Detailed Description
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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 YQFM is proved to be effective for treating sepsis (unpublished data).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.

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

Conditions
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Sepsis

Intervention / Treatment
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* Drug: YiQiFuMai
* Drug: 0.9% Normal Saline 250ml


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: YQFM group<br>YQFM 5.2g in 0.9% Normal Saline 250ml IV, about 40 drops per min, once a day. | Drug: YiQiFuMai<br>* 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.<br>|
| Placebo Comparator: Placebo group<br>0.9% Normal Saline 250ml IV, about 40 drops per min. | Drug: 0.9% Normal Saline 250ml<br>* 0.9% Normal Saline 250ml IV, about 40 drops per min.<br>|

What is the study measuring?
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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 |