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Effect of Metformin Use on Mortality in Diabetic and Non Diabetic Patients With Sepsis and Septic Shock.

Primary Purpose

Septic Shock

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Metformin
standardized protocol
Sponsored by
Assiut University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Septic Shock

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • both sexes aged ≥18 years old complaining of sepsis or septic shock with anticipated stay >24 hours, and signed informed consent by patient or next-of-kin.

Exclusion Criteria:

  • Age less than 18 years old, chronic kidney disease stage IV/V (baseline eGFR <30ml/min/1.73m2), patients with acute coronary syndrome, or do not resuscitate order. Patients could be enrolled at any point during their admission.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Active Comparator

    Active Comparator

    Active Comparator

    Arm Label

    Group C: (n=25) control.

    Group D: (n=25) diabetic patients.

    Group ND: (n=25) non-diabetic patients.

    Arm Description

    patients will receive standardized protocol without receiving metformin.

    diabetic patients will receive standardized protocol and receiving metformin 500 mg every 8 hours since admission regardless of their random blood sugar with measurement of random blood sugar every hour and dextrose 25% infusion will be used if needed and also insulin infusion will be used when appropriate with target random blood sugar 140-180 in diabetic patients.

    patients will receive standardized protocol and receiving metformin 500 mg every 8 hours since admission regardless of their random blood sugar with measurement of random blood sugar every hour and dextrose 25% infusion will be used if needed and also insulin infusion will be used when appropriate with target random blood sugar 100-140 in non diabetic patients.

    Outcomes

    Primary Outcome Measures

    28 day Mortality.
    death within 28 day of sepsis and septic shock where the occurrence of sepsis is hour 0 day 0.

    Secondary Outcome Measures

    Plasma rennin concentration (pg/ml) will be measured on admission and at one week.
    IL6 concentration (ng/ml) will be measured on admission and at one week.
    Level of inflammatory mediators on admission and at 1 week after admission.
    Serum lactate concentration (mmol/L) will be measured on admission and at one week.

    Full Information

    First Posted
    October 3, 2022
    Last Updated
    October 6, 2022
    Sponsor
    Assiut University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05572060
    Brief Title
    Effect of Metformin Use on Mortality in Diabetic and Non Diabetic Patients With Sepsis and Septic Shock.
    Official Title
    Effect of Metformin Use on Mortality in Diabetic and Non Diabetic Patients With Sepsis and Septic Shock.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 1, 2022 (Anticipated)
    Primary Completion Date
    December 31, 2024 (Anticipated)
    Study Completion Date
    January 31, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Assiut University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    We aimed to determine if metformin use in both diabetic and non diabetic patients with sepsis and septic shock affects 28 day mortality and its effect on inflammatory markers. Plasma rennin, serum lactate concentration and IL6 will be measured for predicting 28 days in-hospital mortality in patients with sepsis.
    Detailed Description
    Sepsis, is a life-threatening condition arises when the body's response to infection causes injury to its own tissues, followed by suppression of the immune system. Signs and symptoms include fever, increased heart rate, increased breathing rate, and confusion.There may be symptoms of a specific infection, such as cough, or painful urination. Sepsis is caused by many organisms including bacteria, viruses and fungi. . Risk factors include extreme of ages, a weakened immune system. Previously, a sepsis diagnosis required the presence of at least two systemic inflammatory response syndrome criteria. Sepsis requires immediate treatment with intravenous fluids and antimicrobials in ICU. If fluids is not enough to maintain blood pressure, the use of medications that raise blood pressure becomes necessary. Mechanical ventilation and dialysis may be needed. A central venous catheter and an arterial catheter may be placed. corticosteroid use is controversial. Metformin is a biguanide antihyperglycemic agent. It works by decreasing glucose production in the liver, by increasing the insulin sensitivity of body tissues, and by increasing GDF15 secretion, which reduces appetite. Metformin is a first-line therapy for type 2 diabetes mellitus, taken by mouth and well tolerated. Common adverse effects include diarrhea, nausea, and abdominal pain. Metformin inhibit pathways linked to inflammation, immune reactions, mammalian target of rapamycin (mTOR) signaling, and cell senescence. Some of the changes were confirmed by Western blot. Therefore, metformin prevented part of the deleterious actions of pro-inflammatory cytokines in human β-cells, which was accompanied by islet proteome modifications.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Septic Shock

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare Provider
    Allocation
    Randomized
    Enrollment
    75 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Group C: (n=25) control.
    Arm Type
    Active Comparator
    Arm Description
    patients will receive standardized protocol without receiving metformin.
    Arm Title
    Group D: (n=25) diabetic patients.
    Arm Type
    Active Comparator
    Arm Description
    diabetic patients will receive standardized protocol and receiving metformin 500 mg every 8 hours since admission regardless of their random blood sugar with measurement of random blood sugar every hour and dextrose 25% infusion will be used if needed and also insulin infusion will be used when appropriate with target random blood sugar 140-180 in diabetic patients.
    Arm Title
    Group ND: (n=25) non-diabetic patients.
    Arm Type
    Active Comparator
    Arm Description
    patients will receive standardized protocol and receiving metformin 500 mg every 8 hours since admission regardless of their random blood sugar with measurement of random blood sugar every hour and dextrose 25% infusion will be used if needed and also insulin infusion will be used when appropriate with target random blood sugar 100-140 in non diabetic patients.
    Intervention Type
    Drug
    Intervention Name(s)
    Metformin
    Intervention Description
    Patient screening will be done using SOFA scoring and NEWS Supplemental oxygen will be supplied. Intubation and mechanical ventilation may be required Venous access will be established.CBC, chemistries, liver function tests,coagulation studies ,Peripheral blood cultures, urinalysis, microbiological cultures from suspected sources (eg, sputum, urine,etc),(ABG) and serum lactate will be obtained Crystalloids will be given at 30 mL/kg, started by one hour and completed within three hours Empiric antibiotic therapy is targeted at the suspected organism(s) In patients with lactic acidosis and severe acidemia, Sodium bicarbonate will be used to maintain the arterial pH above 7.15 In patients having persistent hypoperfusion vasopressors will be added Evaluation of volume status will be done using straight leg raising test and ultrasound guided IVC collapsibility index Plasma rennin, serum lactate and IL6 concentrations will be measured on admission and at one week.
    Intervention Type
    Other
    Intervention Name(s)
    standardized protocol
    Intervention Description
    standardized protocol
    Primary Outcome Measure Information:
    Title
    28 day Mortality.
    Description
    death within 28 day of sepsis and septic shock where the occurrence of sepsis is hour 0 day 0.
    Time Frame
    28 day.
    Secondary Outcome Measure Information:
    Title
    Plasma rennin concentration (pg/ml) will be measured on admission and at one week.
    Time Frame
    On admission and at 1 week after admission.
    Title
    IL6 concentration (ng/ml) will be measured on admission and at one week.
    Description
    Level of inflammatory mediators on admission and at 1 week after admission.
    Time Frame
    On admission and at 1 week after admission.
    Title
    Serum lactate concentration (mmol/L) will be measured on admission and at one week.
    Time Frame
    On admission and at 1 week after admission.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: both sexes aged ≥18 years old complaining of sepsis or septic shock with anticipated stay >24 hours, and signed informed consent by patient or next-of-kin. Exclusion Criteria: Age less than 18 years old, chronic kidney disease stage IV/V (baseline eGFR <30ml/min/1.73m2), patients with acute coronary syndrome, or do not resuscitate order. Patients could be enrolled at any point during their admission.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Osama Khaled Ahmed Abodeef, resident
    Phone
    +201018089621
    Email
    Miniosama_2010@yahoo.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Abualauon Mohamed Abedalmohsen, MD
    Phone
    +201020170603
    Email
    abualauon77@gmail.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Osama Khaled Ahmed Abodeef, resident
    Organizational Affiliation
    Assiut University
    Official's Role
    Study Chair
    First Name & Middle Initial & Last Name & Degree
    Abualauon Mohamed Abedalmohsen, MD
    Organizational Affiliation
    Assiut University
    Official's Role
    Study Director
    First Name & Middle Initial & Last Name & Degree
    Nagwa Mostafa Ibrahim, MD
    Organizational Affiliation
    Assiut University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    1303622
    Citation
    Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun;101(6):1644-55. doi: 10.1378/chest.101.6.1644.
    Results Reference
    background
    PubMed Identifier
    24745331
    Citation
    Deutschman CS, Tracey KJ. Sepsis: current dogma and new perspectives. Immunity. 2014 Apr 17;40(4):463-75. doi: 10.1016/j.immuni.2014.04.001.
    Results Reference
    background
    PubMed Identifier
    33208389
    Citation
    Sehgal M, Ladd HJ, Totapally B. Trends in Epidemiology and Microbiology of Severe Sepsis and Septic Shock in Children. Hosp Pediatr. 2020 Dec;10(12):1021-1030. doi: 10.1542/hpeds.2020-0174.
    Results Reference
    background
    PubMed Identifier
    31808551
    Citation
    Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y, Pirracchio R, Rochwerg B. Corticosteroids for treating sepsis in children and adults. Cochrane Database Syst Rev. 2019 Dec 6;12(12):CD002243. doi: 10.1002/14651858.CD002243.pub4.
    Results Reference
    background
    PubMed Identifier
    35954309
    Citation
    Giusti L, Tesi M, Ciregia F, Marselli L, Zallocco L, Suleiman M, De Luca C, Del Guerra S, Zuccarini M, Trerotola M, Eizirik DL, Cnop M, Mazzoni MR, Marchetti P, Lucacchini A, Ronci M. The Protective Action of Metformin against Pro-Inflammatory Cytokine-Induced Human Islet Cell Damage and the Mechanisms Involved. Cells. 2022 Aug 8;11(15):2465. doi: 10.3390/cells11152465.
    Results Reference
    background
    PubMed Identifier
    28114553
    Citation
    Raith EP, Udy AA, Bailey M, McGloughlin S, MacIsaac C, Bellomo R, Pilcher DV; Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcomes and Resource Evaluation (CORE). Prognostic Accuracy of the SOFA Score, SIRS Criteria, and qSOFA Score for In-Hospital Mortality Among Adults With Suspected Infection Admitted to the Intensive Care Unit. JAMA. 2017 Jan 17;317(3):290-300. doi: 10.1001/jama.2016.20328.
    Results Reference
    background

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    Effect of Metformin Use on Mortality in Diabetic and Non Diabetic Patients With Sepsis and Septic Shock.

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