Clinical trial

A Randomized Clinical Trial of the Safety and Feasibility of Metformin as a Treatment for Sepsis Induced AKI.

Name

STUDY22120032

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. 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.

Trial arms

Trial start

2023-11-08

Estimated PCD

2026-11-08

Trial end

2026-12-21

Phase

Early phase I

Treatment

Metformin 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°.

Arms:

Metformin 500 mg

Other names:

Glumetza low dose

Metformin 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°.

Arms:

Metformin 1,000 mg

Other names:

Glutzema high dose

Placebo

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°.

Arms:

Placebo

Other names:

Placebo dose

Size

Primary endpoint

The development of metformin associated serious adverse events (mSAE) which will include hyperlactatemia, hypoglycemia, metabolic acidosis and/or gastrointestinal intolerance during the treatment period

Hospital discharge or 30 days, whatever occurs first

Feasibility: Recruitment, retention and adherence

Hospital discharge or 30 days, whatever occurs first

Feasibility: Investigating the reasons for denial of enrollment by patients, surrogates or clinicians

Hospital discharge or 30 days, whatever occurs first

Feasibility: Data accrual and loss to follow-up

Hospital discharge or 30 days, whatever occurs first

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).

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': 'All parties are blinded by participant group.', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 80, 'type': 'ESTIMATED'}}

Updated at

2024-05-16

1 organization

1 product

1 drug

4 indications

Organization

Hernando Gomez

Product

Metformin

Indication

Sepsis