SepsisPhase 2NCT05900284
Safety and Feasibility of Metformin for Sepsis Induced AKI
A Phase 2 study testing Metformin low dose and Metformin high dose in people with Sepsis and Septic Shock, run by Hernando Gomez at 1 site in United States.
Trial summary
Acute kidney injury (AKI) is an independent risk factor for death that affects 10-15% of hospitalized patients and more than 50% of patients admitted to the intensive care unit. Sepsis is the most frequent cause of AKI, affecting 48 million people worldwide every year, and accounting for approximately 11 million of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Septic Shock, Acute Kidney Injury
- What is being tested?
- Metformin low dose and Metformin high dose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Nov 2023to 18 May 2026
- Phase
- Phase 2
- 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
- Age > 18 years
- Admitted to the ICU with sepsis per sepsis 3 criteria (defined as suspected infection or initiation of anti-biotics plus an increase in SOFA ≥ 2 points)
- Available enteral access
Who cannot join
- Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 prior to study drug administration
- Not expected to survive more than 24 hours
- Advanced directive to withhold life-sustaining treatment
- Metformin use in the last 30 days from admission (assessed by medical or refill prescription history, and by medication reconciliation)
- The treating clinician believes that participation in the trial would not be in the best interests of the patient
- Known or suspected pregnancy
Show all 11Show fewer
- On mechanical circulatory support of any kind
- History of allergy to metformin
- Having severe metabolic acidosis defined by a venous or arterial pH < 7.2, with PaCO2 < 45 or PvCO2 < 50 mmHg at the time of enrolment.
- Patients co-enrolled in observational studies will be eligible for enrollment in LiMiT AKI. However, patients enrolled in interventional studies will need to be assessed on an individual basis to define whether the patient will be eligible.
- Children will be excluded from recruitment for this study. Etiologic causes of sepsis, acute kidney injury, and prognostic factors for children differ from those for adults; and for these reasons the proposed study focuses only on the adult population (age 18 years or older).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
About this study
Official title: A Randomized Clinical Trial of the Safety and Feasibility of Metformin as a Treatment for Sepsis Induced AKI.
Acute kidney injury (AKI) is an independent risk factor for death that affects 10-15% of hospitalized patients and more than 50% of patients admitted to the intensive care unit. Sepsis is the most frequent cause of AKI, affecting 48 million people worldwide every year, and accounting for approximately 11 million of annual global deaths. Despite these figures, there are no known therapies to prevent or reverse septic AKI; hence this study aims to establish the safety and feasibility of the implementation of metformin in the treatment of AKI in patients with sepsis.
This study is the first critical step to inform the design of a future, full-scale efficacy randomized clinical trial.
Read the detailed description
Acute kidney injury (AKI) is an independent risk factor for death, that affects 10-15% of hospitalized patients and more than 50% of patients admitted to the intensive care unit. The most frequent cause of AKI is Sepsis which affects 48 million people worldwide every year. Importantly, the 6-8-fold increase in the risk of death that AKI carries in sepsis, may be reversible because patients with sepsis who recover from AKI have similar 1- and 3-year mortality as those without AKI. These data agree with evidence showing that the development of AKI carries far-reaching consequences like remote organ dysfunction and an increased susceptibility to infection. These data suggest that AKI may be in the causal pathway to death from sepsis and that efforts to reverse AKI may improve the survival in patients with sepsis. However, there are no specific therapies to reverse or prevent the development of AKI during sepsis. Investigators have recently demonstrated that AMP-activated protein kinase (AMPK), a ubiquitous master regulator of cell metabolism and energy balance, is critical to protect the kidney from injury and enhance survival during experimental sepsis. Investigators have shown that pharmacologic activation of AMPK protects from AKI and improves survival, while inhibition increases kidney injury and death. Interestingly, metformin, the recommended first-line agent for the treatment of type 2 diabetes mellitus is a known AMPK activator. Based on this, investigators have demonstrated that treatment with metformin decreases mortality during experimental sepsis. Multiple observational human studies also support this idea. Two recent meta-analyses concluded that exposure to metformin was associated with a decreased risk of mortality. Investigators conducted the largest propensity-score matched retrospective study to date and demonstrated that metformin is associated with a decrease in the odds of moderate-severe AKI and death at 90-days, as well as with an increased odds of recovery from AKI. Despite this evidence, several gaps in knowledge remain. First, it is unclear if the protective effect of metformin is due to confounders. Second, it is unknown if the results of available studies are generalizable to non-diabetic patients.
Third, despite a track record of over 60 years of use in diabetic patients, safety has not been established in patients with septic shock. This proposal aims to conduct a randomized, placebo-controlled, feasibility study to establish the safety and feasibility of the use of oral metformin to prevent the development of sepsis-induced acute kidney injury and inform a future full-scale efficacy trial. Our overarching hypothesis is that in treatment of patients with sepsis, metformin is safe and effective in reducing sepsis-induced elevations in AKI biomarkers. Investigators will determine the safety of the use of metformin to treat adult patients with sepsis and will determine the pharmacokinetic profile of oral metformin (Aim 1), the feasibility of implementing this therapy (Aim 2) and estimate the heterogeneity of the effect of metformin on markers of kidney injury/stress and on circulating platelet mitochondrial function (Aim 3). This study is the first critical step to inform the design of a future, full-scale efficacy RCT.
- Conditions
- Sepsis, Septic Shock, Acute Kidney Injury, Metformin
- Being tested
- Metformin low dose, Metformin high dose, Placebo
- Keywords
- Sepsis, Septic Shock, Acute Kidney Injury, Metformin
- Medical subject headings
- Sepsis, Shock, Septic, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin low doseDrug
Also called Glumetza low dose
If randomized to the 500 mg. Metformin arm, a tablet will be administered orally to the study participant twice a day for the initial five days starting on the date of study enrollment. Clinical research coordinators will collect blood and urine samples from study participants in both treatment arms. The blood will be collected at Baseline, Day 1 thru 7, and at hospital discharge or Day 30, whichever occurs first. On Day 2 and Day 5, the blood will be collected at hour-based intervals of 0.5h, 1h, 2h, 4h, 8h, 12h for a pharmacokinetic profile and delivered to the University of Pittsburgh Medical Center Clinical Laboratory for analysis. The remaining blood collection tubes will be delivered to the Clinical Research Biospecimen Core laboratory to be processed, separated into microtubes, and stored at -80°. Urine samples will be collected at Baseline, Day 1, 3, and 5. The urine will be processed, separated into microtubes, and frozen at -80°.
Metformin high doseDrug
Also called Glutzema high dose
If randomized to the 1000 mg. Metformin arm, a tablet will be administered orally to the study participant twice a day for the initial five days starting on the date of study enrollment. Clinical research coordinators will collect blood and urine samples from study participants in both treatment arms. The blood will be collected at Baseline, Day 1 thru 7, and at hospital discharge or Day 30, whichever occurs first. On Day 2 and Day 5, the blood will be collected at hour-based intervals of 0.5h, 1h, 2h, 4h, 8h, 12h for a pharmacokinetic profile and delivered to the University of Pittsburgh Medical Center Clinical Laboratory for analysis. The remaining blood collection tubes will be delivered to the Clinical Research Biospecimen Core laboratory to be processed, separated into microtubes, and stored at -80°. Urine samples will be collected at Baseline, Day 1, 3, and 5. The urine will be processed, separated into microtubes, and frozen at -80°.
PlaceboDrug
Also called Placebo dose
If randomized to the Placebo arm, a tablet will be administered orally to the study participant twice a day for the initial five days starting on the date of study enrollment. Clinical research coordinators will collect blood and urine samples from study participants in both treatment arms. The blood will be collected at Baseline, Day 1 thru 7, and at hospital discharge or Day 30, whichever occurs first. On Day 2 and Day 5, the blood will be collected at hour-based intervals of 0.5h, 1h, 2h, 4h, 8h, 12h for a pharmacokinetic profile and delivered to the University of Pittsburgh Medical Center Clinical Laboratory for analysis. The remaining blood collection tubes will be delivered to the Clinical Research Biospecimen Core laboratory to be processed, separated into microtubes, and stored at -80°. Urine samples will be collected at Baseline, Day 1, 3, and 5. The urine will be processed, separated into microtubes, and frozen at -80°.
| Study group | Role | What they receive |
|---|---|---|
| Metformin 500 mg | Experimental | One 500mg tablet will be administered twice a day for the first (5) days of study treatment. Receives: Drug: Metformin low dose |
| Placebo | Placebo comparator | One inactive tablet will be administered twice a day for the first (5) days of study treatment. Receives: Drug: Placebo |
| Metformin 1,000 mg | Experimental | One 1,000mg tablet will be administered twice a day for the first (5) days of study treatment. Receives: Drug: Metformin high dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
The development of metformin associated serious adverse events (mSAE) which will include hyperlactatemia, hypoglycemia, metabolic acidosis and/or gastrointestinal intolerance during the treatment period
Safety will be measured by monitoring the patient for the development of metformin associated serious adverse events (mSAE) which will include hyperlactatemia, hypoglycemia, metabolic acidosis and/or gastrointestinal intolerance during the treatment period. In addition, patients will be monitored for any adverse event or any significant adverse event.
Measured: Hospital discharge or 30 days, whatever occurs first
Feasibility: Recruitment, retention and adherence
Investigators will quantify the number of patients screened and consented, the number of patients completing the study treatment, and the number of protocol deviations.
Measured: Hospital discharge or 30 days, whatever occurs first
Feasibility: Investigating the reasons for denial of enrollment by patients, surrogates or clinicians
Investigators will identify barriers to implementing the intervention perceived by physicians, patients, or patients' surrogates who decline to participate or who drop out by requesting their feedback.
Measured: Hospital discharge or 30 days, whatever occurs first
Feasibility: Data accrual and loss to follow-up
Investigators will estimate the proportion of randomized patients that achieve complete acquisition of outcome and ancillary data and lost to follow-up, and the proportion of missing data per variable.
Measured: Hospital discharge or 30 days, whatever occurs first
Secondary outcomes (9)
Area under the curve of the concentration of the renal biomarker TIMP2 (Time Point 2)/ Insulin-like growth factor-binding protein (IGFBP7) in time
Investigators will measure the area under the curve of concentration of the tubular biomarker TIMP2/IGFBP7 vs. time using levels at baseline, day 1, 3 and 5.
Measured: Baseline, Day 1, 3, 5 to define the area under the concentration curve
Pharmacokinetic Accumulation Profile
Metformin accumulation levels will be assessed from study blood samples day 5 blood obtained at 0.5h, 1h, 2h, 4h, 8h, 12h, after administration of the last dose of Metformin.
Measured: Day 5
Pharmacokinetic Absorption Profile
Metformin absorption kinetics will be assessed from study blood samples on Day 2, blood will be obtained at 0.5h, 1h, 2h, 4h, 8h, 12h, after first dose administration of Metformin.
Measured: Day 2
Change in Platelet Mitochondrial Respiration
Platelet bioenergetic profile will be assessed by measuring the oxygen consumption rate in the presence of sequential blockade of the different components of the electron transport chain using the SeaHorse analyzer on a subset of participants from each treatment arm.
Measured: Change from baseline, Day 1, 3, 5
Change in Platelet Mitochondrial Electron Transport Chain Complex Expression
Platelet mitochondrial transport chain complex expression will be quantified by western blot using a LI-COR machine normalized to the Integrin alfa-2b protein.
Measured: Change from baseline, Day 1, 3, 5
Acute Kidney Injury at day 7
AKI will be measured using the worse creatinine and urine output daily for 7 days and at discharge or day 30, whichever comes first.
Measured: At day 7
Acute Kidney Injury at day 30 or discharge
AKI will be measured using the worse creatinine and urine output daily for 7 days and at discharge or day 30, whichever comes first.
Measured: Hospital discharge or day 30, whichever comes first.
Number of patients requiring Renal Replacement Therapy within the hospitalization
Participants will be assessed on the need for any form of intermittent or continuous renal replacement therapy.
Measured: Hospital discharge or 30 days, whichever comes first.
In-hospital Mortality
The proportion of patients who died while in the hospital
Measured: Hospital discharge or Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2023
- Study start8 Nov 2023
- Primary completion18 May 2026
- Study completion18 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- One 500mg or 1,000mg tablet will be administered twice a day for the first (5) days of study treatment. One inactive tablet will be administered twice a day for the first (5) days of study treatment
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hernando Gomez
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor-investigator, Hernando Gomez, University of Pittsburgh
- Investigators
- Hernando Gomez, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05900284
- Sponsor's protocol ID
- STUDY22120032
- Other IDs
- 1R01DK133142-01A1
- Status last verified
- Jun 2026
- First submitted
- 22 May 2023
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The LiMiT-AKI study investigators will review the request for data from other investigators. The investigators will execute a data-sharing agreement with the University of Pittsburgh to share de-identified data with other investigators for research purposes only. The data sharing agreement will (ensure: i) a commitment to using the data only for research purposes and not to identify any individual data.
Publications
Saraiva IE, Hamahata N, Huang DT, Kane-Gill SL, Rivosecchi RM, Shiva S, Nolin TD, Chen X, Minturn J, Chang CH, Li X, Kellum J, Gomez H. Metformin for sepsis-associated AKI: a protocol for the Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI). BMJ Open. 2024 Apr 30;14(4):e081120. doi: 10.1136/bmjopen-2023-081120.
PubMed 38688665
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Clinical Trial of the Safety and Feasibility of Metformin as a Treatment for Sepsis Induced AKI.
- ClinicalTrials.gov ID
- NCT05900284
- Acronym / sponsor ID
- STUDY22120032
- Conditions
- Sepsis, Septic Shock, Acute Kidney Injury, Metformin
- Keywords
- Sepsis, Septic Shock, Acute Kidney Injury, Metformin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Hernando GomezUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 8 Nov 2023 (actual)
- Primary completion
- 18 May 2026 (actual)
- Study completion
- 18 May 2026 (actual)
- First posted
- 12 Jun 2023 (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.
Acute kidney injury (AKI) is an independent risk factor for death that affects 10-15% of hospitalized patients and more than 50% of patients admitted to the intensive care unit. Sepsis is the most frequent cause of AKI, affecting 48 million people worldwide every year, and accounting for approximately 11 million of annual global deaths. Despite these figures, there are no known therapies to prevent or reverse septic AKI; hence this study aims to establish the safety and feasibility of the implementation of metformin in the treatment of AKI in patients with sepsis.
This study is the first critical step to inform the design of a future, full-scale efficacy randomized clinical trial.
Detailed description
Acute kidney injury (AKI) is an independent risk factor for death, that affects 10-15% of hospitalized patients and more than 50% of patients admitted to the intensive care unit. The most frequent cause of AKI is Sepsis which affects 48 million people worldwide every year. Importantly, the 6-8-fold increase in the risk of death that AKI carries in sepsis, may be reversible because patients with sepsis who recover from AKI have similar 1- and 3-year mortality as those without AKI. These data agree with evidence showing that the development of AKI carries far-reaching consequences like remote organ dysfunction and an increased susceptibility to infection. These data suggest that AKI may be in the causal pathway to death from sepsis and that efforts to reverse AKI may improve the survival in patients with sepsis. However, there are no specific therapies to reverse or prevent the development of AKI during sepsis. Investigators have recently demonstrated that AMP-activated protein kinase (AMPK), a ubiquitous master regulator of cell metabolism and energy balance, is critical to protect the kidney from injury and enhance survival during experimental sepsis. Investigators have shown that pharmacologic activation of AMPK protects from AKI and improves survival, while inhibition increases kidney injury and death. Interestingly, metformin, the recommended first-line agent for the treatment of type 2 diabetes mellitus is a known AMPK activator. Based on this, investigators have demonstrated that treatment with metformin decreases mortality during experimental sepsis. Multiple observational human studies also support this idea. Two recent meta-analyses concluded that exposure to metformin was associated with a decreased risk of mortality. Investigators conducted the largest propensity-score matched retrospective study to date and demonstrated that metformin is associated with a decrease in the odds of moderate-severe AKI and death at 90-days, as well as with an increased odds of recovery from AKI. Despite this evidence, several gaps in knowledge remain. First, it is unclear if the protective effect of metformin is due to confounders. Second, it is unknown if the results of available studies are generalizable to non-diabetic patients.
Third, despite a track record of over 60 years of use in diabetic patients, safety has not been established in patients with septic shock. This proposal aims to conduct a randomized, placebo-controlled, feasibility study to establish the safety and feasibility of the use of oral metformin to prevent the development of sepsis-induced acute kidney injury and inform a future full-scale efficacy trial. Our overarching hypothesis is that in treatment of patients with sepsis, metformin is safe and effective in reducing sepsis-induced elevations in AKI biomarkers. Investigators will determine the safety of the use of metformin to treat adult patients with sepsis and will determine the pharmacokinetic profile of oral metformin (Aim 1), the feasibility of implementing this therapy (Aim 2) and estimate the heterogeneity of the effect of metformin on markers of kidney injury/stress and on circulating platelet mitochondrial function (Aim 3). This study is the first critical step to inform the design of a future, full-scale efficacy RCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- One 500mg or 1,000mg tablet will be administered twice a day for the first (5) days of study treatment. One inactive tablet will be administered twice a day for the first (5) days of study treatment
| Arm | Type | Receives |
|---|---|---|
| Metformin 500 mg | Experimental | Drug: Metformin low doseOne 500mg tablet will be administered twice a day for the first (5) days of study treatment. |
| Placebo | Placebo comparator | Drug: PlaceboOne inactive tablet will be administered twice a day for the first (5) days of study treatment. |
| Metformin 1,000 mg | Experimental | Drug: Metformin high doseOne 1,000mg tablet will be administered twice a day for the first (5) days of study treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age > 18 years
- Admitted to the ICU with sepsis per sepsis 3 criteria (defined as suspected infection or initiation of anti-biotics plus an increase in SOFA ≥ 2 points)
- Available enteral access
Key exclusion criteria (11 listed)
- Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 prior to study drug administration
- Not expected to survive more than 24 hours
- Advanced directive to withhold life-sustaining treatment
- Metformin use in the last 30 days from admission (assessed by medical or refill prescription history, and by medication reconciliation)
- The treating clinician believes that participation in the trial would not be in the best interests of the patient
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 |
|---|---|---|
| Metformin low doseAlso: Glumetza low doseIf randomized to the 500 mg. Metformin arm, a tablet will be administered orally to the study participant twice a day for the initial five days starting on the date of study enrollment. Clinical research coordinators will collect blood and urine samples from study participants in both treatment arms. The blood will be collected at Baseline, Day 1 thru 7, and at hospital discharge or Day 30, whichever occurs first. On Day 2 and Day 5, the blood will be collected at hour-based intervals of 0.5h, 1h, 2h, 4h, 8h, 12h for a pharmacokinetic profile and delivered to the University of Pittsburgh Medical Center Clinical Laboratory for analysis. The remaining blood collection tubes will be delivered to the Clinical Research Biospecimen Core laboratory to be processed, separated into microtubes, and stored at -80°. Urine samples will be collected at Baseline, Day 1, 3, and 5. The urine will be processed, separated into microtubes, and frozen at -80°. | Drug | Metformin 500 mg |
| Metformin high doseAlso: Glutzema high doseIf randomized to the 1000 mg. Metformin arm, a tablet will be administered orally to the study participant twice a day for the initial five days starting on the date of study enrollment. Clinical research coordinators will collect blood and urine samples from study participants in both treatment arms. The blood will be collected at Baseline, Day 1 thru 7, and at hospital discharge or Day 30, whichever occurs first. On Day 2 and Day 5, the blood will be collected at hour-based intervals of 0.5h, 1h, 2h, 4h, 8h, 12h for a pharmacokinetic profile and delivered to the University of Pittsburgh Medical Center Clinical Laboratory for analysis. The remaining blood collection tubes will be delivered to the Clinical Research Biospecimen Core laboratory to be processed, separated into microtubes, and stored at -80°. Urine samples will be collected at Baseline, Day 1, 3, and 5. The urine will be processed, separated into microtubes, and frozen at -80°. | Drug | Metformin 1,000 mg |
| PlaceboAlso: Placebo doseIf randomized to the Placebo arm, a tablet will be administered orally to the study participant twice a day for the initial five days starting on the date of study enrollment. Clinical research coordinators will collect blood and urine samples from study participants in both treatment arms. The blood will be collected at Baseline, Day 1 thru 7, and at hospital discharge or Day 30, whichever occurs first. On Day 2 and Day 5, the blood will be collected at hour-based intervals of 0.5h, 1h, 2h, 4h, 8h, 12h for a pharmacokinetic profile and delivered to the University of Pittsburgh Medical Center Clinical Laboratory for analysis. The remaining blood collection tubes will be delivered to the Clinical Research Biospecimen Core laboratory to be processed, separated into microtubes, and stored at -80°. Urine samples will be collected at Baseline, Day 1, 3, and 5. The urine will be processed, separated into microtubes, and frozen at -80°. | Drug | Placebo |
Primary outcome
The development of metformin associated serious adverse events (mSAE) which will include hyperlactatemia, hypoglycemia, metabolic acidosis and/or gastrointestinal intolerance during the treatment period
Time frame: Hospital discharge or 30 days, whatever occurs first
Safety will be measured by monitoring the patient for the development of metformin associated serious adverse events (mSAE) which will include hyperlactatemia, hypoglycemia, metabolic acidosis and/or gastrointestinal intolerance during the treatment period. In addition, patients will be monitored for any adverse event or any significant adverse event.
Feasibility: Recruitment, retention and adherence
Time frame: Hospital discharge or 30 days, whatever occurs first
Investigators will quantify the number of patients screened and consented, the number of patients completing the study treatment, and the number of protocol deviations.
Feasibility: Investigating the reasons for denial of enrollment by patients, surrogates or clinicians
Time frame: Hospital discharge or 30 days, whatever occurs first
Investigators will identify barriers to implementing the intervention perceived by physicians, patients, or patients' surrogates who decline to participate or who drop out by requesting their feedback.
Feasibility: Data accrual and loss to follow-up
Time frame: Hospital discharge or 30 days, whatever occurs first
Investigators will estimate the proportion of randomized patients that achieve complete acquisition of outcome and ancillary data and lost to follow-up, and the proportion of missing data per variable.
9 secondary outcomes
Area under the curve of the concentration of the renal biomarker TIMP2 (Time Point 2)/ Insulin-like growth factor-binding protein (IGFBP7) in time
Time frame: Baseline, Day 1, 3, 5 to define the area under the concentration curve
Pharmacokinetic Accumulation Profile
Time frame: Day 5
Pharmacokinetic Absorption Profile
Time frame: Day 2
Change in Platelet Mitochondrial Respiration
Time frame: Change from baseline, Day 1, 3, 5
Change in Platelet Mitochondrial Electron Transport Chain Complex Expression
Time frame: Change from baseline, Day 1, 3, 5
Acute Kidney Injury at day 7
Time frame: At day 7
Acute Kidney Injury at day 30 or discharge
Time frame: Hospital discharge or day 30, whichever comes first.
Number of patients requiring Renal Replacement Therapy within the hospitalization
Time frame: Hospital discharge or 30 days, whichever comes first.
In-hospital Mortality
Time frame: Hospital discharge or Day 30
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
- Results publication: PubMed 38688665Saraiva IE, Hamahata N, Huang DT, Kane-Gill SL, Rivosecchi RM, Shiva S, Nolin TD, Chen X, Minturn J, Chang CH, Li X, Kellum J, Gomez H. Metformin for sepsis-associated AKI: a protocol for the Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI). BMJ Open. 2024 Apr 30;14(4):e081120. doi: 10.1136/bmjopen-2023-081120.
- BMJ Open Full Published ArticleLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The LiMiT-AKI study investigators will review the request for data from other investigators. The investigators will execute a data-sharing agreement with the University of Pittsburgh to share de-identified data with other investigators for research purposes only. The data sharing agreement will (ensure: i) a commitment to using the data only for research purposes and not to identify any individual data.
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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.
Hernando Gomez, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin low dose and Metformin high dose in people with Sepsis and Septic Shock, run by Hernando Gomez at 1 site in United States.
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 3 inclusion and 11 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: finished, as of the sponsor's last update on 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The development of metformin associated serious adverse events (mSAE) which will include hyperlactatemia, hypoglycemia, metabolic acidosis and/or gastrointestinal intolerance during the treatment period (time frame: Hospital discharge or 30 days, whatever occurs first). The study lists 4 primary outcomes in all. 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 NCT05900284, which also lists 1 linked publication.
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 9 Jun 2026.