Sepsis Clinical Trial
Official title:
A Randomized Clinical Trial of the Safety and Feasibility of Metformin as a Treatment for Sepsis Induced AKI.
Verified date | May 2024 |
Source | University of Pittsburgh |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Enrolling by invitation |
Enrollment | 80 |
Est. completion date | December 21, 2026 |
Est. primary completion date | November 8, 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Age > 18 years 2. 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) 3. Available enteral access Exclusion Criteria: 1. Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 prior to study drug administration 2. Not expected to survive more than 24 hours 3. Advanced directive to withhold life-sustaining treatment 4. Metformin use in the last 30 days from admission (assessed by medical or refill prescription history, and by medication reconciliation) 5. The treating clinician believes that participation in the trial would not be in the best interests of the patient 6. Known or suspected pregnancy 7. On mechanical circulatory support of any kind 8. History of allergy to metformin 9. 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). |
Country | Name | City | State |
---|---|---|---|
United States | University of Pittsburgh | Pittsburgh | Pennsylvania |
Lead Sponsor | Collaborator |
---|---|
Hernando Gomez | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) |
United States,
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 Metf — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | Hospital discharge or 30 days, whatever occurs first | |
Primary | 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. | Hospital discharge or 30 days, whatever occurs first | |
Primary | 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. | Hospital discharge or 30 days, whatever occurs first | |
Primary | 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. | Hospital discharge or 30 days, whatever occurs first | |
Secondary | 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. | Baseline, Day 1, 3, 5 to define the area under the concentration curve | |
Secondary | 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. | Day 5 | |
Secondary | 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. | Day 2 | |
Secondary | 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. | Change from baseline, Day 1, 3, 5 | |
Secondary | 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. | Change from baseline, Day 1, 3, 5 | |
Secondary | 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. | At day 7 | |
Secondary | 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. | Hospital discharge or day 30, whichever comes first. | |
Secondary | 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. | Hospital discharge or 30 days, whichever comes first. | |
Secondary | In-hospital Mortality | The proportion of patients who died while in the hospital | Hospital discharge or Day 30 |
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