Septic ShockNCT05572060
Effect of Metformin Use on Mortality in Diabetic and Non Diabetic Patients With Sepsis and Septic Shock.
A study testing Metformin and standardized protocol in people with Septic Shock, run by Assiut University.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Metformin and standardized protocol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2022to 31 Jan 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet.
About this study
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.
Read the 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.
- Conditions
- Septic Shock
- Being tested
- Metformin, standardized protocol
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
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.
standardized protocolOther
standardized protocol
| Study group | Role | What they receive |
|---|---|---|
| Group C: (n=25) control. | Active comparator | patients will receive standardized protocol without receiving metformin. Receives: Other: standardized protocol |
| Group D: (n=25) diabetic patients. | Active comparator | 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. Receives: Drug: Metformin; Other: standardized protocol |
| Group ND: (n=25) non-diabetic patients. | Active comparator | 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. Receives: Drug: Metformin; Other: standardized protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
28 day Mortality.
death within 28 day of sepsis and septic shock where the occurrence of sepsis is hour 0 day 0.
Measured: 28 day.
Secondary outcomes (3)
Plasma rennin concentration (pg/ml) will be measured on admission and at one week.
Measured: On admission and at 1 week after admission.
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.
Measured: On admission and at 1 week after admission.
Serum lactate concentration (mmol/L) will be measured on admission and at one week.
Measured: On admission and at 1 week after admission.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2022
- Study start1 Dec 2022 (estimated)
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Osama Khaled Ahmed Abodeef, Assiut University
- Investigators
- Osama Khaled Ahmed Abodeef, resident, Study chair, Assiut UniversityAbualauon Mohamed Abedalmohsen, MD, Study director, Assiut UniversityNagwa Mostafa Ibrahim, MD, Principal investigator, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05572060
- Sponsor's protocol ID
- Metformin use in sepsis
- Status last verified
- Oct 2022
- First submitted
- 3 Oct 2022
- Last updated
- 7 Oct 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 1303622Deutschman 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.
PubMed 24745331Sehgal 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.
PubMed 33208389Annane 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.
PubMed 31808551Giusti 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.
PubMed 35954309Raith 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.
PubMed 28114553
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Metformin Use on Mortality in Diabetic and Non Diabetic Patients With Sepsis and Septic Shock.
- ClinicalTrials.gov ID
- NCT05572060
- Acronym / sponsor ID
- Metformin use in sepsis
- Conditions
- Septic Shock
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Dec 2022 (estimated)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Jan 2025 (estimated)
- First posted
- 7 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group C: (n=25) control. | Active comparator | Other: standardized protocolpatients will receive standardized protocol without receiving metformin. |
| Group D: (n=25) diabetic patients. | Active comparator | Drug: Metformin, Other: standardized protocoldiabetic 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. |
| Group ND: (n=25) non-diabetic patients. | Active comparator | Drug: Metformin, Other: standardized protocolpatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminPatient 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. | Drug | Group D: (n=25) diabetic patients., Group ND: (n=25) non-diabetic patients. |
| standardized protocolstandardized protocol | Other | Group C: (n=25) control., Group D: (n=25) diabetic patients., Group ND: (n=25) non-diabetic patients. |
Primary outcome
28 day Mortality.
Time frame: 28 day.
death within 28 day of sepsis and septic shock where the occurrence of sepsis is hour 0 day 0.
3 secondary outcomes
Plasma rennin concentration (pg/ml) will be measured on admission and at one week.
Time frame: On admission and at 1 week after admission.
IL6 concentration (ng/ml) will be measured on admission and at one week.
Time frame: On admission and at 1 week after admission.
Serum lactate concentration (mmol/L) will be measured on admission and at one week.
Time frame: On admission and at 1 week after admission.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2022.
- Background: PubMed 1303622Bone 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.
- Background: PubMed 24745331Deutschman 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.
- Background: PubMed 33208389Sehgal 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.
- Background: PubMed 31808551Annane 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.
- Background: PubMed 35954309Giusti 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.
- Background: PubMed 28114553Raith 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.
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Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Osama Khaled Ahmed Abodeef, resident study chair
Assiut University
Abualauon Mohamed Abedalmohsen, MD study director
Assiut University
Nagwa Mostafa Ibrahim, MD principal investigator
Assiut University
Questions about this trial
What is this clinical trial studying?
A study testing Metformin and standardized protocol in people with Septic Shock, run by Assiut University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Osama Khaled Ahmed Abodeef, resident (+201018089621, Miniosama_2010@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
28 day Mortality. (time frame: 28 day.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05572060, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2022.