Improvement of Organ Function by Apigenin in Elderly Patients With Sepsis

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

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.

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

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.

Intragastric tube injection of ground apigenin tablet 50 mg with 5 ml of sterilized water + conventional standardized treatment, for 4 consecutive days.

Gastric tube injection of 5 ml of sterilized water for injection + conventional standardized treatment, for 4 consecutive days.

Intragastric tube injection of ground apigenin tablet 50 mg with 5 ml of sterilized water + conventional standardized treatment, for 4 consecutive days.

Intragastric tube injection of 5 ml of sterilized water + conventional standardized treatment, for 4 consecutive days.

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 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)

oxygenation index(PaO2/FiO2),the patients treated with extracorporeal membrane oxygenation will not collect this indicator

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)

A adverse event refers to any adverse medical event that occur after the intervention of trial. The adverse events are not necessarily causally related to the trial treatment.

Any adverse medical event occurs at any dose that meets one or more of the following criteria: 1. causes death 2.life-threatening 3. requires hospitalization or hospitalization for an extended period of time 4. causes permanent or significant disability and functional defects 5. causes deformity.

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.

The datasets generated and analyzed during the study are available from the corresponding author on reasonable request.