Metformin and Lactoferrin in Sepsis in Icu

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Sepsis

Intervention / Treatment
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* Drug: Metformin
* Drug: Lactoferrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria: Age more than 18 years old. A diagnosis of sepsis according to the latest Sepsis definition.11 Estimated GFR &gt;45 ml/minute. Exclusion Criteria: Exclusion Criteria: Pregnancy and breast feeding. End stage hepatic disease. End stage renal disease -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sepsis, metformin, lactoferrin