Metformin and Lactoferrin in Sepsis in Icu

Comparative Study to Evaluate the Safety and Possible Efficacy of Metformin Versus Lactoferrin in ICU Patients With

Sepsis is a life-threatening organ dysfunction triggered by an unregulated response of a host to infection. Sepsis is a reason for substantial mortality and morbidity among intensive care unit (ICU) patients. 1 Therefore, the aim of our study is to compare the safety and efficacy of metformin and lactoferrin in ICU patients with sepsis.

Study Overview

• Status: Recruiting
• Conditions: Sepsis
• Intervention / Treatment: Drug: Metformin; Drug: Lactoferrin

Detailed Description

Sepsis is a life-threatening organ dysfunction triggered by an unregulated response of a host to infection. Sepsis is a reason for substantial mortality and morbidity among intensive care unit (ICU) patients. 1 The pathophysiology of sepsis has changed spectacularly over the last several decades. Significant comprehension into the components of the inflammatory response has been achieved. Inflammation contributes to endothelial injury and initiates coagulation pathways.2 The inflammatory reaction is mediated by the release of cytokines (tumor necrosis factor-alpha, interleukins, and prostaglandins) from neutrophils and macrophages. The cytokines trigger the extrinsic coagulation cascade and inhibit fibrinolysis. These overlapping processes end with organ dysfunction.3 The Sequential Organ Failure Assessment or SOFA score was developed to assess the acute morbidity of critical illness at a population level and has been extensively validated as a tool for this purpose across a range of healthcare settings and environments.4 Metformin is oral anti-diabetic agent that has positive effects such as antioxidant and anti-inflammatory properties which are considered potentially beneficial properties for management of septic patients. Previous studies showed that preadmission metformin use may reduce mortality in adult patients with sepsis and diabetes mellitus. Therefore, our study aims to test the potential efficacy of metformin in all subsets of patient with sepsis.5,6 Lactoferrin is a cationic glycoprotein and associated with many activities including the relevant anti-inflammatory one, especially associated to the downregulation of pro-inflammatory cytokines besides its anti-microbial and immunomodulatory effect.7 A previous study suggested that lactoferrin supplementation to enteral feeds with or without probiotics decreases late-onset sepsis in preterm infants without adverse effects and this encourage us to test its role in adult patients with sepsis.8 Therefore, the aim of our study is to compare the safety and efficacy of metformin and lactoferrin in ICU patients with sepsis.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Alaa Hemida; Phone Number: 667867; Email: Alaa.hemida@pharm.tanta.efu.eg
• Study Contact Backup: Name: Alaa Hemida; Phone Number: 35677

Study Locations

• Egypt
  • Tanta, Egypt
    • Recruiting
    • Tanta

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Inclusion Criteria:

  1. Age more than 18 years old.
  2. A diagnosis of sepsis according to the latest Sepsis definition.11
  3. Estimated GFR >45 ml/minute.

Exclusion Criteria:

Exclusion Criteria:

1. Pregnancy and breast feeding.
2. End stage hepatic disease.
3. End stage renal disease -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group1: Metformin; Group1: (Metformin, n=30) who will receive metformin 500 mg three times daily.	Drug: Metformin; metformin 500 mg
Active Comparator: Group 2 :Lactoferrin; Group 2 :(Lactoferrin, n=30) who will receive lactoferrin 100 mg three times daily	Drug: Lactoferrin; lactoferrin 100 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint is mortality rate	28 days

Collaborators and Investigators

• Sponsor: Tanta University
• Investigators: Principal Investigator: Alaa Hemida, Tanta university

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): June 9, 2024
• Study Completion (Estimated): June 9, 2024

Study Registration Dates

• First Submitted: December 4, 2023
• First Submitted That Met QC Criteria: December 12, 2023
• First Posted (Actual): December 26, 2023

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: sepsis; metformin; lactoferrin
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Infective Agents; Metformin; Lactoferrin
• Other Study ID Numbers: metformin and lactoferrin

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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