Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery.

Phase 3

Completed

• Conditions: Cardiac Surgery
• Interventions: Drug: Amino Acids; Drug: Placebos

• Registration Number: NCT03709264
• Lead Sponsor: Università Vita-Salute San Raffaele

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-10-09
• Study First Submitted QC: 2018-10-15
• Study First Posted: 2018-10-17
• Study Start: 2019-10-07
• Primary Completion: 2024-01-17
• Status Verified: 2025-01
• Study Completion: 2025-01-17
• Last Update Submitted: 2025-01-27
• Last Update Posted: 2025-01-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3511

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Amino Acids infusion	Amino Acids	-
Placebo	Placebos	-

Primary Outcome Measures

Name	Time	Method
AKI incidence	Until hospital discharge, an average of 10 days	Incidence of Acute Kidney Injury during hospital stay

Secondary Outcome Measures

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

Trial Locations

Locations (22)

National University Hospital; 🇸🇬 Singapore, Singapore

AOU Policlinico Paolo Giaccone; 🇮🇹 Palermo, Italy

Grande Ospedale Metropolitano; 🇮🇹 Reggio Calabria, Italy

IRCCS Cardiologico Monzino; 🇮🇹 Milano, Lombardy, Italy

Ospedale Ordine Mauriziano; 🇮🇹 Torino, Piemonte, Italy

Ospedale del cuore - Fondazione Toscana Gabriele Monasterio; 🇮🇹 Massa, Toscana, Italy

Istituto Clinico Humanitas; 🇮🇹 Rozzano, Lombardy, Italy

Ospedale San Carlo; 🇮🇹 Potenza, Basilicata, Italy

IRCCS Ospedale San Donato; 🇮🇹 Miano, Milano, Italy

Città della Salute; 🇮🇹 Torino, Piemonte, Italy

Ospedale San Raffaele; 🇮🇹 Milano, Italy

Ospedale Santa Maria della Misericordia; 🇮🇹 Udine, Italy

Magdalena Clinic for Cardiovascular Diseases; 🇭🇷 Zagreb, Croatia

University Hospital Dubrava; 🇭🇷 Dubrava, Croatia

Ospedale Mater Domini; 🇮🇹 Catanzaro, Calabria, Italy

Ospedale Monaldi; 🇮🇹 Napoli, Campania, Italy

Pineta Grande Hospital; 🇮🇹 Castel Volturno, Caserta, Italy

Azienda Ospedaliera Sant'Andrea; 🇮🇹 Roma, Lazio, Italy

Ospedale San Camillo; 🇮🇹 Roma, Lazio, Italy

IRCCS San Martino Istitute; 🇮🇹 Genova, Liguria, Italy

Maria Cecilia Hospital; 🇮🇹 Cotignola, Ravenna, Italy

Azienda Ospedaliera Universitaria Pisana; 🇮🇹 Pisa, Italy