Ignite Creation Date:
2024-05-06 @ 7:08 PM
Last Modification Date:
2024-10-26 @ 3:00 PM
Study NCT ID:
NCT05900284
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2024-05-16
First Post:
2023-05-22
Brief Title:
Safety and Feasibility of Metformin for Sepsis Induced AKI
Sponsor:
Hernando Gomez
Organization:
University of Pittsburgh
Study Overview
Official Title:
A Randomized Clinical Trial of the Safety and Feasibility of Metformin as a Treatment for Sepsis Induced AKI
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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
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 injurystress 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
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 injurystress 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 1R01DK133142-01A1 | NIH | None | httpsreporternihgovquickSearch1R01DK133142-01A1 |