Clinical trial NCT05572060: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Septic Shock
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2022-10-07
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 28 day Mortality.
timeFrame: 28 day.
Secondary outcomes:
measure: Plasma rennin concentration (pg/ml) will be measured on admission and at one week.
timeFrame: On admission and at 1 week after admission.
measure: IL6 concentration (ng/ml) will be measured on admission and at one week.
timeFrame: On admission and at 1 week after admission.
measure: Serum lactate concentration (mmol/L) will be measured on admission and at one week.
timeFrame: On admission and at 1 week after admission.
Other outcomes:
Locations:
Study officials:
affiliation: Assiut University
name: Osama Khaled Ahmed Abodeef, resident
role: STUDY_CHAIR
affiliation: Assiut University
name: Abualauon Mohamed Abedalmohsen, MD
role: STUDY_DIRECTOR
affiliation: Assiut University
name: Nagwa Mostafa Ibrahim, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.