Clinical trial NCT04019184: Reduction of Occurence of Acute Kidney Injury (AKI) Through Administration of Glutamine
Official title: Biomarker-guided Implementation of Glutamine to Reduce the Occurence of AKI After Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiac Surgery
Acute Kidney Injury
Keywords: Cardiac surgery
glutamine
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: Fresenius Kabi
name: IZKF (Interdisciplinary Centre for Clinical Research (IZKF), Muenster)
First posted: 2019-07-15
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate whether the application of glutamine versus control in patients with high risk for AKI identified by biomarkers can reduce kidney damage after cardiac surgery.

Detailed description: Cardiac surgery is characterized by an increased production of free radicals as a consequence of surgical trauma, ischemia-reperfusion injury, inflammatory response syndrome in response to the use of the extracorporeal circulation. This results in an increased production and release of free radicals which may lead to an exhaustion of antioxidants and organ failure since the lungs, kidneys, liver and gastrointestinal tract are particularly susceptible to reactive oxidant species. Glutamine is considered as a conditionally indispensable amino acid in catabolic states of critically ill patients. It belongs, together with other mediators, to the host defense as major intracellular direct free radical scavengers. Its depletion has been demonstrated to be an independent predictor of mortality in a group of ICU (intensive care unit) patients. Clinical studies showed a positive outcome effect. In animal models, glutamine reduces the occurrence of AKI after ischemia-reperfusion injury. This could be demonstrated through reduced functional markers as well as reduced renal biomarker levels. Preliminary data suggest that glutamine has pleiotropic effects since it has effects on the immune system (reduced expression of cytokines) as well as on tubular epithelial cells (unpublished animal data from our laboratory).

Thus, a randomized-controlled trial to analyze the effects of glutamine supplementation in high risk patients identified by renal biomarkers undergoing cardiac surgery with cardiopulmonary bypass (CPB) on the effects of kidney damage is urgently needed.

Eligibility criteria: Inclusion Criteria:

* Adult patients undergoing cardiac surgery with CPB
* Urinary \[TIMP-2\]\*\[IGFBP7\] \>= 0.3 4h after CPB
* Written informed consent

Exclusion Criteria:

* Preexisting AKI (stage 1 and higher)
* Patients with cardiac assist devices
* Pregnant women, nursing women and women of childbearing potential
* Known (Glomerulo-) Nephritis, interstitial nephritis or vasculitis
* Chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) \< 30 ml/min
* Dialysis dependent CKD
* Prior kidney transplant within the last to 12 months
* Hypersensitivity to the active substance, or to any of the excipients of the study medication
* Hepatic insufficiency
* Severe metabolic acidosis (pH \< 7.2)
* Participation in another intervention trial in the past 3 months
* Persons with any kind of dependency on the investigator or employed by the institution responsible or investigator
* Persons held in an institution by legal or official order

Primary outcomes:
measure: Kidney damage after cardiac surgery identified by measuring biomarkers ([TIMP-2]*[IGFBP7]
timeFrame: 12 hours after cardiac surgery
Secondary outcomes:
measure: Occurence of acute kidney injury according to the KDIGO (Kidney Disease: Improving Global Outcomes) criteria
timeFrame: 72 hours after end of cardiac surgery
measure: Severity of acute kidney injury (number of patients with KDIGO stage 1, KDIGO stage 2 or KDIGO stage 3)
timeFrame: 72 hours after end of cardiac surgery
measure: Creatinine Clearance
timeFrame: one day after cardiac surgery
measure: Free-days of vasoactive medications and mechanical ventilation
timeFrame: 28 days after cardiac surgery
measure: Renal recovery
timeFrame: 30 days after cardiac surgery
measure: Renal recovery
timeFrame: 60 days after cardiac surgery
measure: Renal recovery
timeFrame: 90 days after cardiac surgery
measure: Mortality
timeFrame: 30 days after cardiac surgery
measure: Mortality
timeFrame: 60 days after cardiac surgery
measure: Mortality
timeFrame: 90 days after cardiac surgery
measure: ICU and Hospital stay
timeFrame: up to 90 days after cardiac surgery (until discharge)
measure: Number of patients with renal replacement therapy
timeFrame: up to 90 days after cardiac surgery
Other outcomes:
Locations:
city: Münster
country: Germany
facility: University Hospital Münster
Study officials:
affiliation: University Hospital Muenster, Dept. of Anesthesiology, Intensive Care and Pain Medicine
name: Alexander Zarbock, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: