Efficacy of Fuzheng Tongfu Jiedu Prescription for Treating Gastrointestinal Dysfunction Associated With Sepsis (FZTFJD)

The Clinical Effect and Mechanism of Fuzheng Tongfu Jiedu Prescription Regulating Cell Pyrodeath in the Treatment of Gastrointestinal Dysfunction in Sepsis Based on mtDNA/NLRP3/Caspase-1/GSDMD Signaling Pathway

This study is a single-center, randomized, double-blind, placebo-controlled trial.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastrointestinal Dysfunction; Traditional Chinese Medicine; Sepsis Abdominal
• Intervention / Treatment: Drug: Fuzheng Tongfu Jiedu prescription (FZTFJD); Drug: Placebo

Detailed Description

The study is designed to evaluate efficacy and safety of FZTFJD for treating gastrointestinal dysfunction associated with sepsis compared to placebo in combination with conventional western medicine treatment. Participants included in this study are diagnosed with sepsis-induced gastrointestinal dysfunction classified as Acute gastrointestinal injury (AGI)grades I-III. A total of seventy patients will be randomly assigned in a 1:1 ratio to receive either FZTFJD or placebo. The study encompasses a treatment duration of seven days followed by a twenty-one-day safety follow-up period. The AGI grade as the primary outcome measure will be assessed, while gut symptom score, abdominal pressure and circumference, SOFA and APACHE II scores, inflammation level as well as intestinal barrier function will serve as secondary outcome measures. Additionally, length of ICU stay and 28-day mortality will be included as prognostic indicators in this study.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xue ting Han; Phone Number: +86-01084012709; Email: 529607340@qq.com

Study Locations

• China
  • Beijing
    • BeiJing, Beijing, China, 100700
      • Ethics Committee of Dongzhimen Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Clinical diagnosis of sepsis-induced gastrointestinal dysfunction with Acute AGI grade I-III.
2. 50-90 years old, regardless of gender.
3. Sequential Organ Failure Assessment (SOFA) score ≥ 2.
4. Diagnosed with sepsis-induced gastrointestinal dysfunction within 24 hours.
5. Voluntary participation with signed informed consent.

Exclusion Criteria:

1. ICU length of stay ≤ 3 days (due to death, discharge, or transfer), rendering gastrointestinal function evaluation unfeasible.
2. Patients with allergies or allergic constitution to the investigational herbal medications.
3. Inability to measure intra-abdominal pressure or abdominal circumference due to obesity (weight > 150 kg), trauma, or surgical factors.
4. Severe organic diseases: lower gastrointestinal bleeding, malignancies, cirrhosis, chronic renal failure (uremic stage), hematologic disorders, HIV, etc.
5. History of gastrointestinal surgery.
6. Long-term use of corticosteroids or immunosuppressants.
7. Severe psychiatric disorders or inability to cooperate with trial protocols.
8. Participation in other clinical trials within 30 days.
9. Pregnant or lactating women.
10. Participated in other clinical studies in the past 3 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fuzheng Tongfu Jiedu prescription (FZTFJD); Basic treatment + Fuzheng Tongfu Jiedu prescription	Drug: Fuzheng Tongfu Jiedu prescription (FZTFJD); Fuzheng Tongfu Jiedu prescription (FZTFJD), a kind of Traditional Chinese medicine (TCM).Conventional Western medical treatment in accordance with the "2021 International Guidelines for the Management of Sepsis and Septic Shock." . This included treatment and resuscitation begin immediately, administering antimicrobials immediately, hemodynamic management, mechanical ventilation, organ support, nutritional support, and prophylaxis for acute ulcers.; Other Names: Conventional Western medical treatment
Placebo Comparator: Placebo; Basic treatment + Fuzheng Tongfu Jiedu prescription placebo	Drug: Placebo; Fuzheng Tongfu Jiedu prescription plaebo. Conventional Western medical treatment in accordance with the "2021 International Guidelines for the Management of Sepsis and Septic Shock." . This included treatment and resuscitation begin immediately, administering antimicrobials immediately, hemodynamic management, mechanical ventilation, organ support, nutritional support, and prophylaxis for acute ulcers.; Other Names: Conventional Western medical treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AGI grade	As a predictor of mortality in critically ill patients, AGI grade is useful for identifying the severity of GI dysfunction. AGI grade refers to the diagnostic criteria for acute gastrointestinal injury established by the European Critical Care Society in 2012. AGI can be graded from a minimum of I to a maximum of IV. The higher the level, the more severe the gastrointestinal dysfunctionHigher AGI grade levels indicate progressively more severe conditions.	Day0, Day3,Day7,Day14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastrointestinal symptoms score	The gastrointestinal symptoms score will be assessed by GSRS scale. The total score of the GSRS scale ranges from 0 to 78, with higher scores indicating more severe gastrointestinal symptoms.	Day0, Day3,Day7,Day14
Abdominal pressure	Abdominal pressure is measured by bladder pressure which is measured by water column method.Higher abdominal pressure levels indicate progressively more severe conditions.	Day0, Day3,Day7,Day14
Abdominal circumference	At the end of exhalation and before the beginning of inhalation, the abdominal circumference through the center of the umbilical cord was measured with a soft ruler.	Day0, Day3,Day7,Day14
Blood routine	Blood routine test will be determined by blood cell analyzer.White blood cells higher or lower than normal indicate a septic inflammatory state.	Day0, Day3,Day7,Day14
CRP	Expression levels of C-reactive proteins will be measured by Elida kit. The higher the level, the higher the sepsis inflammation.	Day0, Day3,Day7,Day14
PCT	Expression levels of Procalcitonin will be measured with a specific kit. The higher the level, the higher the sepsis inflammation.	Day0, Day3,Day7,Day14
Immune index-T cell functional subsets	The expression level of T cell functional subsets was detected	Day0,Day7
Immune index-lymphocyte subsets	The expression level of lymphocyte subsets was detected	Day0, Day7
Intestinal barrier function-diamine oxidase（DAO）	DAO is an important marker of intestinal mucosal integrity, and its activity level can reflect the strength of intestinal barrier function. When the gut is damaged, DAO is released into the blood, resulting in elevated DAO levels in the blood.The expression level of DAO in serum will be deteceed by the Eliasa kit.	Day0, Day7
Intestinal barrier function-D-lactic acid level	The expression level of serum D-lactic acid will be measured by a specific Elisa kit. D-lactic acid is produced by bacteria in the gastrointestinal tract and then absorbed into the bloodstream. An increase of D-lactic acid indicates increased damage to the intestinal barrier and increased intestinal permeability in patients with sepsis.	Day0, Day7
Intestinal barrier function--intestinal type Fatty acid Binding Protein (FABP)	Serum midgut fatty acid-binding protein (I-FABP) expression levels will be detected by a specific elisa kit. I-FABP is located in the cytoplasm of mature intestinal cells in the small intestinal villi, and ischemia of the intestinal villi can release I-FABP into the blood circulation. The increase of I-FABP in serum indicates increased intestinal ischemia.	Day0、 Day7
Intestinal barrier function-Citrulline (CIT)	Since citrulline is mostly synthesized in intestinal mucosal epithelial cells, the number and function of intestinal mucosal epithelial cells can be evaluated by detecting the serum citrulline concentration. Therefore, monitoring the serum citrulline concentration can evaluate the intestinal function and the severity of intestinal dysfunction in critically ill patients.The expression level of CIT level in serum will be deteceed by the Eliasa kit.Since citrulline is mostly synthesized in intestinal mucosal epithelial cells, the number and function of intestinal mucosal epithelial cells can be evaluated by detecting the serum citrulline concentration. The decrease of serum citrulline level can reflect the decrease of intestinal mucosal epithelial cells.	Day0、 Day7
Severity of sepsis-SOFA score	The score of SOFA will be assessed according to the SOFA scale. The total SOFA score is derived by adding the scores of the six organ systems and ranges from 0 to 24 points. The higher the score, the more severe the patient's organ dysfunction and the worse the prognosis.	Day0、 Day3、Day7、Day14
Severity of sepsis-APACHE Ⅱ	The score of APACHE Ⅱ will be assessed according to the APACHE Ⅱ scale. The APACHEⅡ scoring system is composed of acute physiology score (APS), age score, and three parts. The final score is the sum of the three parts. The maximum theoretical score is 71, the higher the score, the more severe the disease.	Day0、 Day3、Day7、Day14
Length of ICU stay	The length of ICU stay is closely related to sepsis condition, prognosis and medical expenditure. The longer the ICU stay, the worse the prognosis and the higher the medical expenditure.	Day28
28-day mortality	The 28-day mortality rate intuitively reflects the prognosis of sepsis.	Day28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety index-Blood routine	Blood routine will be detected by test kit.	Day0、 Day3、Day7、Day14
Safety index-liver function	The indexes related to liver function metabolism, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct and indirect bilirubin, albumin, prealbumin and cholinesterase, will be detected by biochemical test	Day0、 Day3、Day7、Day14
Safety index-Renal function	Renal function test will be detected by test kit.	Day0、 Day3、Day7、Day14
Safety index-Stool routine	Stool routine will be detected by test kit.	Day0、 Day3、Day7、Day14
Adverse event	Adverse event	Record any abnormality during the intervention.
Mechanism discussion-mtDNA	The expression level of mtDNA in seum will be detected by test kit.	Day0、 Day7
Mechanism discussion-NLRP3	The expression level of NLRP3 in seum will be detected by test kit.	Day0、 Day7
IL-1β	The expression level of IL-1β in seum will be detected by test kit.	Day0、 Day7
IL-18	The expression level of IL-18 in seum will be detected by test kit.	Day0、 Day7
IL-17	The expression level of IL-17 in seum will be detected by test kit.	Day0、 Day7

Collaborators and Investigators

• Sponsor: Dongzhimen Hospital, Beijing
• Collaborators: Beijing University of Chinese Medicine
• Investigators: Study Chair: Jin Liu, Dr, ICU Dongzhimen Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 25, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: March 20, 2025
• First Submitted That Met QC Criteria: April 11, 2025
• First Posted (Actual): April 18, 2025

Study Record Updates

• Last Update Posted (Actual): April 18, 2025
• Last Update Submitted That Met QC Criteria: April 11, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: sepsis; Traditional Chinese medicine; gastrointestinal dysfunction; Fuzheng Tongfu Jiedu Decoction
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: DZMG-QNZX-24008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The results will be shared with sleep researchers, public, and relevant academic institutions through high-impact peer-reviewed publications.
• IPD Sharing Time Frame: Six months after the end of the study
• IPD Sharing Access Criteria: ljhly05@163.com
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

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