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.

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Other: apigenin; Other: sterilized water

Detailed Description

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:

1. Department of Critical Care Medicine of Zhujiang Hospital, Guangzhou, Guangdong, China Primary endpoint: 96-hour Sequential Organ Failure Assessment (SOFA) score

   Secondary endpoints:

2. The state of inflammatory response: the serum level of interleukin-6(IL-6) and C-reactive protein (CRP) at 96 h after randomization.
3. The state of liver function: the serum level of transaminase (AST#ALT) #total bilirubin at 96 h after randomization.
4. The state of lung function: oxygenation index (PaO2/FiO2) at 96h after Randomization.
5. The state of kidney function: the serum level of Creatinine (Cr)#blood urea nitrogen (BUN)# at 96 h after randomization.
6. The state of infection: the serum level of procalcitonin (PCT) at 96 h after randomization.
7. The state of circulation system: the serum level of lactate at 96 h after Randomization.
8. The duration of successful cessation of supportive therapies for organ dysfunction including vasoactive agents, mechanical ventilation.
9. The daily urine output#duration of continuous renal replacement therapy (CRRT) #fluid balance.
10. The length of stay in ICU.

Safety endpoints:

1. adverse events
2. Serious adverse events

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guanzhou, Guangdong, China
      • Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. age ≥65 years;
2. meeting the diagnostic criteria of the 2016 International Sepsis Guidelines;
3. subjects who voluntarily participated in this study and signed an informed consent form.

Exclusion Criteria:

1. patients who are allergic to the study products;
2. patients who are unable to feed via gastrointestinal nutrition tube.

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	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.	The outcome will be assessed at the 28 day after enrollment
Incidence of serious adverse events	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.	The outcome will be assessed at the 28 day after enrollment

Collaborators and Investigators

• Sponsor: Zhujiang Hospital
• Investigators: Principal Investigator: Zhanguo Liu, M.D.PhD, Department of Critical Care Medicine of Zhujiang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Actual): January 5, 2024
• Study Completion (Actual): January 5, 2024

Study Registration Dates

• First Submitted: August 11, 2023
• First Submitted That Met QC Criteria: August 13, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: septic shock; sepsis; apigenin
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Toxemia; Shock, Septic
• Other Study ID Numbers: 2023-KY-085-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The datasets generated and analyzed during the study are available from the corresponding author on reasonable request.

Drug and device information, study documents

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