Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery.

Study Overview
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Brief Summary
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To date, no pharmacological agents are proven efficacious in treating perioperative AKI. There is a strong biological rationale for the administration of amino acid in the management of patients at risk of AKI with increases in renal blood flow and GFR of 25 to 60% for several hours after the administration of amino acids (Woods LL 1993) mediated by a afferent arteriolar dilation.(Meyer TW 1983) Moreover, animal models have demonstrated that an increase in renal blood flow in response to a short-term amino acid infusion can protect the kidney from acute ischemic insults. Finally, these nephro-protective effects are preserved in critical illness. Cardiac surgery appears to be the best setting to test the likely beneficial renal effects of amino acid because of pathophysiological principles and the ability to intervene before the injury has begun. Although the etiology of AKI in cardiac surgery is multifactorial, renal hypoperfusion is believed to play a major role in this development by decreasing renal perfusion through a reduction in renal blood flow and through the activation of the sympathetic nervous system and the renin-angiotensin system with afferent arteriolar vasoconstriction. In this setting, a global increase in renal blood flow by means of Amino Acid therapy appears a logical and promising intervention. The primary aim of the study is to determine whether providing continuous infusion of a balanced mixture of amino acids, compared to placebo (balanced crystalloid solution), reduces the incidence of acute kidney injury (AKI) in patients scheduled for cardiac surgery defined as KDIGO stage 1 or greater during hospital stay.

Official Title
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Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery: a Multi-centre Randomized Blinded Placebo Controlled Clinical Trial.

Conditions
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Cardiac Surgery

Intervention / Treatment
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* Drug: Amino Acids
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 18 years scheduled cardiac surgery expected to stay in ICU at least 1 night after surgery signed informed consent Exclusion Criteria: Patient currently enrolled into another randomized clinical trial Patient currently receiving or scheduled for intermittent or continuous renal replacement therapy Patients with CKD of equal or more than CKD stage IV (GFR<30 ml/min/1.73 m2) Patient with a kidney transplant Patient is not expected to survive ICU or hospital discharge Patient previously been enrolled and randomized into this study Patient has severe liver disease (Child-Pugh score >7 points) Patient has a hypersensitivity (known allergy) to one or more of the included amino acids Patient has a congenital alteration of amino acid metabolism Pregnant or currently breastfeeding patients Patients with any of the contraindications reported in the summary product characteristics.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amino Acids infusion<br> | Drug: Amino Acids<br>* Patients randomized to experimental arm receive a continuous infusion of a balanced mixture of amino acids in a dose of 2 g/kg ideal body weight/day (to a maximum 100 g/day) from the operating room admission up to either death, start of RRT, ICU discharge or 72 hours after treatment initiation, trough a central venous line<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebos<br>* Placebo: standard treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AKI incidence | Incidence of Acute Kidney Injury during hospital stay | Until hospital discharge, an average of 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | All-cause mortality at ICU discharge, hospital discharge, 30 and 90 and 180 days after randomization | 180 days | 
| RRT | Need and duration of renal replacement therapy | 180 days | 
| ICU stay | Duration of Intensive Care Unit stay | Until ICU discharge, an average of 2 days | 
| Hospital stay | Duration of hospital stay | Until hospital discharge, an average of 10 days | 
| Mechanical Ventilation | Need and duration of mechanical ventilation | Until ICU discharge, an average of 2 days | 
| EQ-5D | Quality of life at 180 days after randomization as measured by the EQ-5D | 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney protection, acute kidney injury, cardiac surgery, amino acids, mortality, ICU