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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury; Cardiac Surgery
• Intervention / Treatment: Drug: L-Alanyl/L-Glutamine; Drug: Placebo

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since it has effects on the immune system (reduced expression of cytokines) as well as on tubular epithelial cells (unpublished animal data from our laboratory).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

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Münster, Germany, 48149
    • University Hospital Münster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Glutamine group; Intravenous infusion of 0.5 g/kg body weight (2.5 ml/kg body weight) L-alanyl-Lglutamine over 12 h after randomization	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_COMPARATOR: Control group; Intravenous infusion of 2.5 ml/kg body weight sodium chloride 0.9 % over 12 h after randomization	Drug: Placebo; Immediately after randomization (not longer than 30 min after fulfilling eligibility criteria), patients will receive intravenous infusions with the placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		30 days after cardiac surgery
Mortality		60 days after cardiac surgery
Mortality		90 days after cardiac surgery
Occurence of acute kidney injury according to the KDIGO (Kidney Disease: Improving Global Outcomes) criteria		72 hours after end of cardiac surgery
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
Creatinine Clearance		one day after cardiac surgery
Free-days of vasoactive medications and mechanical ventilation		28 days after cardiac surgery
Renal recovery	Renal recovery is defined as serum creatinine levels < 0.5 mg/dL higher than baseline serum creatinine	30 days after cardiac surgery
Renal recovery	Renal recovery is defined as serum creatinine levels < 0.5 mg/dL higher than baseline serum creatinine	60 days after cardiac surgery
Renal recovery	Renal recovery is defined as serum creatinine levels < 0.5 mg/dL higher than baseline serum creatinine	90 days after cardiac surgery
ICU and Hospital stay		up to 90 days after cardiac surgery (until discharge)
Number of patients with renal replacement therapy		up to 90 days after cardiac surgery

Collaborators and Investigators

• Sponsor: University Hospital Muenster
• Collaborators: Fresenius Kabi; IZKF (Interdisciplinary Centre for Clinical Research (IZKF), Muenster)
• Investigators: Principal Investigator: Alexander Zarbock, MD, PhD, University Hospital Muenster, Dept. of Anesthesiology, Intensive Care and Pain Medicine

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 18, 2019
• Primary Completion (ACTUAL): February 13, 2020
• Study Completion (ACTUAL): May 13, 2020

Study Registration Dates

• First Submitted: July 4, 2019
• First Submitted That Met QC Criteria: July 12, 2019
• First Posted (ACTUAL): July 15, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 20, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Cardiac surgery; glutamine
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: UKM17_0035; 2018-002832-25 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No