Reduction of Occurence of Acute Kidney Injury (AKI) Through Administration of Glutamine

Acute Kidney Injury Clinical Trial

— Glacé  

Official title:

Biomarker-guided Implementation of Glutamine to Reduce the Occurence of AKI After Cardiac Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04019184
• Other study ID #: UKM17_0035
• Secondary ID: 2018-002832-25
• Status: Completed
• Phase: Phase 3
• Start date: July 18, 2019
• Est. completion date: May 13, 2020

Study information

• Verified date: May 2020
• Source: University Hospital Muenster
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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since it has effects on the immune system (reduced expression of cytokines) as well as on tubular epithelial cells (unpublished animal data from our laboratory).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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: May 13, 2020
• Est. primary completion date: February 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Cardiac Surgery

Intervention

Drug:
• L-Alanyl/L-Glutamine
Immediately after randomization (not longer than 30 min after fulfilling eligibility criteria), patients will receive intravenous infusions with the investigational drug
• Placebo
Immediately after randomization (not longer than 30 min after fulfilling eligibility criteria), patients will receive intravenous infusions with the placebo

Locations

Country	Name	City	State
Germany	University Hospital Münster	Münster

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Muenster	Fresenius Kabi, IZKF (Interdisciplinary Centre for Clinical Research (IZKF), Muenster)

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kidney damage after cardiac surgery identified by measuring biomarkers ([TIMP-2]*[IGFBP7]	The presence of tissue inhibitor of metalloproteinases (TIMP-2) and insulin-like grwoth-factor binding protein 7 (IGFBP7) in the urine will be measured.	12 hours after cardiac surgery
Secondary	Occurence of acute kidney injury according to the KDIGO (Kidney Disease: Improving Global Outcomes) criteria		72 hours after end of cardiac surgery
Secondary	Severity of acute kidney injury (number of patients with KDIGO stage 1, KDIGO stage 2 or KDIGO stage 3)	Definition and classification of acute injury according to the KDIGO (Kidney Disease Improving Global Outcomes) clinical practice guidelines on acute kidney injury	72 hours after end of cardiac surgery
Secondary	Creatinine Clearance		one day after cardiac surgery
Secondary	Free-days of vasoactive medications and mechanical ventilation		28 days after cardiac surgery
Secondary	Renal recovery	Renal recovery is defined as serum creatinine levels < 0.5 mg/dL higher than baseline serum creatinine	30 days after cardiac surgery
Secondary	Renal recovery	Renal recovery is defined as serum creatinine levels < 0.5 mg/dL higher than baseline serum creatinine	60 days after cardiac surgery
Secondary	Renal recovery	Renal recovery is defined as serum creatinine levels < 0.5 mg/dL higher than baseline serum creatinine	90 days after cardiac surgery
Secondary	Mortality		30 days after cardiac surgery
Secondary	Mortality		60 days after cardiac surgery
Secondary	Mortality		90 days after cardiac surgery
Secondary	ICU and Hospital stay		up to 90 days after cardiac surgery (until discharge)
Secondary	Number of patients with renal replacement therapy		up to 90 days after cardiac surgery