Safety and Feasibility of Metformin for Sepsis Induced AKI

Launched by HERNANDO GOMEZ · Jun 2, 2023

Keywords

ClinConnect Summary

The LiMiT AKI trial is a small, early-stage study to see if metformin can be safely used to treat or prevent kidney injury that can happen in people with sepsis (a serious infection). In this randomized, double-blind study, adults in the ICU with sepsis are assigned to one of three groups for the first 5 days: metformin 500 mg twice daily, metformin 1000 mg twice daily, or a placebo (inactive pill). The main goal is to assess safety—watching for metformin-related problems such as lactic acidosis, low blood sugar, stomach issues, or other adverse events—and to see if this approach is feasible enough to test in a larger trial later. The study will also collect early data on how metformin behaves in the body and on kidney-related markers to guide future research.

Who can participate? Adults 18 and older who are in the ICU with sepsis and have a way to receive medicine by a tube (enteral access) are eligible, as long as their kidney function is not severely reduced at the start (eGFR 30 mL/min/1.73 m2 or higher) and they don’t have conditions that would make participation unsafe (for example, very short expected survival, pregnancy, certain heart or kidney problems, or recent metformin use). If enrolled, you would receive one of the three treatments for 5 days and have regular blood and urine tests. Blood samples will be drawn more often on Days 2 and 5 to study how metformin is absorbed and cleared. Participants are watched closely for side effects and kidney function is checked through Day 7 and again around Day 30 or at discharge. The study is led by the University of Pittsburgh and aims to enroll about 80 people; results will help decide whether a larger trial is warranted.

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Eligibility criteria

• 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).