Improvement of Organ Function by Apigenin in Elderly Patients With Sepsis

Study Overview
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Brief Summary
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In this single-center, randomized, single-blind, placebo-controlled pilot clinical trial. The effect of apigenin on the improvement of organ function will be investigated in elderly patients with sepsis. Researchers will screen patients admitted to the Department of Critical Care Medicine at Zhujiang Hospital to identify patients with sepsis based on including and excluding criteria and obtain informed consent and randomize them into groups. The treatment group will be given apigenin tablets 50mg ground with 5ml of sterilized water for intra-gastric tube injection; the control group will be given an equal volume of sterilized water for intra-gastric tube injection. The changes in SOFA score and other clinically meaningful outcomes in 4 days will be collected.

Detailed Description
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Investigational drug: Apigenin Study title: Improvement of Organ function by Apigenin in Elderly Patients With Sepsis: A Single-center, Single-blind, Randomized, Placebo-controlled, pilot Clinical Trial Principal Investigator: Zhanguo Liu, professor, Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University Study subjects: Elderly septic/septic shock patients who meet the diagnostic criteria of the 2016 International Sepsis Guidelines. Study objectives: The objective of the study is to determine whether apigenin, compared to placebo, improves organ dysfunction scores (SOFA scores) in elderly septic patients. Study design: A single-center, single-blind, randomized, placebo-controlled pilot Clinical Trial. Method: Apigenin group: Intragastric tube injection of ground apigenin tablet 50 mg with 5 ml of sterilized water + conventional standardized treatment, for 4 days or until ICU discharge. Placebo control group: Gastric tube injection of 5 ml of sterilized water for injection + conventional standardized treatment, for 4 days or ICU discharge. Course: 4 days Sample size: 20 The number of study center: 1 Study center: Department of Critical Care Medicine of Zhujiang Hospital, Guangzhou, Guangdong, China Primary endpoint: 96-hour Sequential Organ Failure Assessment (SOFA) score Secondary endpoints: The state of inflammatory response: the serum level of interleukin-6(IL-6) and C-reactive protein (CRP) at 96 h after randomization. The state of liver function: the serum level of transaminase (AST#ALT) #total bilirubin at 96 h after randomization. The state of lung function: oxygenation index (PaO2/FiO2) at 96h after Randomization. The state of kidney function: the serum level of Creatinine (Cr)#blood urea nitrogen (BUN)# at 96 h after randomization. The state of infection: the serum level of procalcitonin (PCT) at 96 h after randomization. The state of circulation system: the serum level of lactate at 96 h after Randomization. The duration of successful cessation of supportive therapies for organ dysfunction including vasoactive agents, mechanical ventilation. The daily urine output#duration of continuous renal replacement therapy (CRRT) #fluid balance. The length of stay in ICU. Safety endpoints: adverse events Serious adverse events

Official Title
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Improvement of Organ Function by Apigenin in Elderly Patients With Sepsis: A Single-center, Single-blind, Randomized, Placebo-controlled, Pilot Clinical Trial

Conditions
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Sepsis, Septic Shock

Intervention / Treatment
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* Other: apigenin
* Other: sterilized water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥65 years; meeting the diagnostic criteria of the 2016 International Sepsis Guidelines; subjects who voluntarily participated in this study and signed an informed consent form. Exclusion Criteria: patients who are allergic to the study products; patients who are unable to feed via gastrointestinal nutrition tube.

Ages Eligible for Study
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Minimum Age: 65 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
Interventional Model Description: Treatment group: Intragastric tube injection of ground apigenin tablet 50 mg with 5 ml of sterilized water + conventional standardized treatment, for 4 days or ICU discharge. Control group: Intragastric tube injection of ground apigenin tablet 50 mg with 5 ml of sterilized water + conventional standardized treatment, for 4 days or ICU discharge.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: apigenin<br>Intragastric tube injection of ground apigenin tablet 50 mg with 5 ml of sterilized water + conventional standardized treatment, for 4 consecutive days. | Other: apigenin<br>* Intragastric tube injection of ground apigenin tablet 50 mg with 5 ml of sterilized water + conventional standardized treatment, for 4 consecutive days.<br>|
| Placebo Comparator: sterilized water<br>Gastric tube injection of 5 ml of sterilized water for injection + conventional standardized treatment, for 4 consecutive days. | Other: sterilized water<br>* Intragastric tube injection of 5 ml of sterilized water + conventional standardized treatment, for 4 consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 96-hour Sequential Organ Failure Assessment (SOFA) score | The SOFA score is the Sequential Organ Failure Score, which is used to assess a patient's prognosis by determining the degree of impairment of major organ function. The score is divided into 6 sections: respiratory, coagulation, hepatic, cardiovascular, central nervous system, and renal, and ranges from 0 to 4, with higher SOFA scores associated with a higher incidence of poor prognosis. | The outcome will be assessed at the 0,1,2,3,4 day after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| inflammatory response(1) | the serum level of C-reactive protein(CRP) | The outcome will be assessed at the 0,1,2,3,4 day after enrollment | 
| inflammatory response(2) | the serum level of interleukin-6(IL-6) | The outcome will be assessed at the 0,1,2,3,4 day after enrollment | 
| Duration of use of vasoactive drugs | The duration from the vasoactive drugs administration to the successful cessation in hours( The successful cessation is defined as the attainment of a clinician-prescribed mean arterial pressure target for more than 24-hours without the use of vasoactive drugs.This outcome measure is intended only for patients receiving vasoactive drugs) | The outcome will be assessed at the 0,1,2,3,4 day after enrollment | 
| liver function(1) | the serum level of Alanine transaminase(ALT) | The outcome will be assessed at the 0,1,2,3,4 day after enrollment | 
| liver function(2) | the serum level of Aspartate transaminase (AST) | The outcome will be assessed at the 0,1,2,3,4 day after enrollment | 
| liver function(3) | the serum level of total bilirubin(TBil) | The outcome will be assessed at the 0,1,2,3,4 day after enrollment | 
| lung function | oxygenation index(PaO2/FiO2),the patients treated with extracorporeal membrane oxygenation will not collect this indicator | The outcome will be assessed at the 0,1,2,3,4 day after enrollment | 
| kidney function(1) | serum level of Creatinine (Cr) | The outcome will be assessed at the 0,1,2,3,4 day after enrollment | 
| kidney function(2) | serum level of blood urea nitrogen(BUN) | The outcome will be assessed at the 0,1,2,3,4 day after enrollment | 
| Indicators of infection | the serum level of procalcitonin(PCT) | The outcome will be assessed at the 0,1,2,3,4 day after enrollment | 
| The level of lactate | the serum level of lactic acid | The outcome will be assessed at the 0,1,2,3,4 day after enrollment | 
| The Duration of use of mechanical ventilation (MV) | The duration from the MV administration to the successful cessation in hours( The successful cessation is defined as the termination of MV for more than 48-hours. This outcome measure is intended only for patients receiving MV) | The outcome will be assessed at the 28 day after enrollment | 
| The duration of CRRT | The duration of CRRT therapy in hours | The outcome will be assessed at the 28 day after enrollment | 
| Daily urine output | Daily urine output in milliliters from 0:00 - 24:00 | The outcome will be assessed at the 1,2,3,4 day after enrollment | 
| fluid balance | Net fluid intake and output in 24 hours | The outcome will be assessed at the 1,2,3,4 day after enrollment | 
| The length of ICU stay | ICU length of ICU stay | The outcome will be assessed at the 28 day after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sepsis, apigenin, septic shock