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

NCT ID: NCT04019184

Last Updated: 2020-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-18
• Study Completion Date: 2020-05-13

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since it has effects on the immune system (reduced expression of cytokines) as well as on tubular epithelial cells (unpublished animal data from our laboratory).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

Conditions

Cardiac Surgery; Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

L-Alanyl/L-Glutamine

Intervention Type: DRUG

Immediately after randomization (not longer than 30 min after fulfilling eligibility criteria), patients will receive intravenous infusions with the investigational drug

Control group

Intravenous infusion of 2.5 ml/kg body weight sodium chloride 0.9 % over 12 h after randomization

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Immediately after randomization (not longer than 30 min after fulfilling eligibility criteria), patients will receive intravenous infusions with the placebo

Interventions

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

Intervention Type: DRUG

Placebo

Immediately after randomization (not longer than 30 min after fulfilling eligibility criteria), patients will receive intravenous infusions with the placebo

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fresenius Kabi

INDUSTRY

Sponsor Role: collaborator

IZKF (Interdisciplinary Centre for Clinical Research (IZKF), Muenster)

UNKNOWN

Sponsor Role: collaborator

University Hospital Muenster

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexander Zarbock, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Muenster, Dept. of Anesthesiology, Intensive Care and Pain Medicine

Locations

University Hospital Münster

Münster, , Germany

Countries

Germany

References

Weiss R, Meersch M, Gerke M, Wempe C, Schafers M, Kellum JA, Zarbock A. Effect of Glutamine Administration After Cardiac Surgery on Kidney Damage in Patients at High Risk for Acute Kidney Injury: A Randomized Controlled Trial. Anesth Analg. 2023 Nov 1;137(5):1029-1038. doi: 10.1213/ANE.0000000000006288. Epub 2022 Nov 29.

Reference Type: DERIVED

PMID: 36730070 (View on PubMed)

Other Identifiers

2018-002832-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UKM17_0035

Identifier Type: -

Identifier Source: org_study_id