Clinical trial NCT03709264: Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery.
Official title: Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery: a Multi-centre Randomized Blinded Placebo Controlled Clinical Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiac Surgery
Keywords: kidney protection
acute kidney injury
cardiac surgery
amino acids
mortality
ICU
Lead sponsor: Università Vita-Salute San Raffaele
Sponsor class: OTHER
First posted: 2018-10-17
Enrollment: 3511
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: AKI incidence
timeFrame: Until hospital discharge, an average of 10 days
Secondary outcomes:
measure: Mortality
timeFrame: 180 days
measure: RRT
timeFrame: 180 days
measure: ICU stay
timeFrame: Until ICU discharge, an average of 2 days
measure: Hospital stay
timeFrame: Until hospital discharge, an average of 10 days
measure: Mechanical Ventilation
timeFrame: Until ICU discharge, an average of 2 days
measure: EQ-5D
timeFrame: 180 days
Other outcomes:
Locations:
city: Dubrava
country: Croatia
facility: University Hospital Dubrava
city: Zagreb
country: Croatia
facility: Magdalena Clinic for Cardiovascular Diseases
city: Potenza
country: Italy
facility: Ospedale San Carlo
state: Basilicata
city: Catanzaro
country: Italy
facility: Ospedale Mater Domini
state: Calabria
city: Napoli
country: Italy
facility: Ospedale Monaldi
state: Campania
city: Castel Volturno
country: Italy
facility: Pineta Grande Hospital
state: Caserta
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea
state: Lazio
city: Roma
country: Italy
facility: Ospedale San Camillo
state: Lazio
city: Genova
country: Italy
facility: IRCCS San Martino Istitute
state: Liguria
city: Milano
country: Italy
facility: IRCCS Cardiologico Monzino
state: Lombardy
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Lombardy
city: Miano
country: Italy
facility: IRCCS Ospedale San Donato
state: Milano
city: Torino
country: Italy
facility: Città della Salute
state: Piemonte
city: Torino
country: Italy
facility: Ospedale Ordine Mauriziano
state: Piemonte
city: Cotignola
country: Italy
facility: Maria Cecilia Hospital
state: Ravenna
city: Massa
country: Italy
facility: Ospedale del cuore - Fondazione Toscana Gabriele Monasterio
state: Toscana
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Palermo
country: Italy
facility: AOU Policlinico Paolo Giaccone
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana
city: Reggio Calabria
country: Italy
facility: Grande Ospedale Metropolitano
city: Udine
country: Italy
facility: Ospedale Santa Maria della Misericordia
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
References:
citation: Losiggio R, Redaelli MB, Landoni G, Bellomo R. Intravenous Amino-acid Infusion to Prevent Acute Kidney Injury after Cardiac Surgery: A Review of the Evidence. Ann Thorac Surg. 2024 Dec 4:S0003-4975(24)01029-4. doi: 10.1016/j.athoracsur.2024.11.020. Online ahead of print.
citation: Baiardo Redaelli M, Landoni G, Monti G, Bellomo R. Amino acids and the kidney; friends or foes? Curr Opin Clin Nutr Metab Care. 2025 Mar 1;28(2):156-159. doi: 10.1097/MCO.0000000000001083. Epub 2024 Oct 21.
citation: Pruna A, Losiggio R, Landoni G, Kotani Y, Redaelli MB, Veneziano M, Lee TC, Zangrillo A, Gaudino MFL, Bellomo R; for Protection Study group. Amino Acid Infusion for Perioperative Functional Renal Protection: A Meta-analysis. J Cardiothorac Vasc Anesth. 2024 Dec;38(12):3076-3085. doi: 10.1053/j.jvca.2024.08.033. Epub 2024 Aug 22.
citation: Landoni G, Brambillasca C, Baiardo Redaelli M, Bradic N, Ti LK, Povsic-Cevra Z, Nepomniashchikh VA, Zoccai GB, D'Ascenzo F, Romagnoli E, Scandroglio AM, Ballotta A, Rondello N, Franco A, Massaro C, Viscido C, Calabro MG, Garofalo E, Canichella F, Monaco F, Severi L, Pisano A, Barucco G, Venditto M, Federici F, Licheri M, Paternoster G, Trompeo A, Belletti A, Mantovani LF, Perone R, Dalessandro G, Kroeller D, Haxhiademi D, Galbiati C, Tripodi VF, Giardina G, Lembo R, Nakhnoukh C, Guarracino F, Longhini F, Bove T, Zangrillo A, Bellomo R, Fominskiy E. Intravenous amino acid therapy for kidney protection in cardiac surgery a protocol for a multi-centre randomized blinded placebo controlled clinical trial. The PROTECTION trial. Contemp Clin Trials. 2022 Oct;121:106898. doi: 10.1016/j.cct.2022.106898. Epub 2022 Aug 28.
citation: Rosario Losiggio, Martina Baiardo Redaelli, Alessandro Pruna, Giovanni Landoni, Rinaldo Bellomo. The renal effects of amino acids infusion. Signa Vitae. 2024. 20(7);1-4.
citation: Bellomo R, Monaco F, Paternoster G. Intravenous Amino Acids and Kidney Protection. Reply. N Engl J Med. 2024 Nov 21;391(20):1965-1966. doi: 10.1056/NEJMc2412012. No abstract available.
citation: Kotani Y, Baiardo Redaelli M, Pruna A, Losiggio R, Cocozza S, Ti LK, Bradic N, Comis M, Landoni G, Bellomo R. Intravenous amino acid for kidney protection: current understanding and future perspectives. Clin Kidney J. 2024 Dec 26;18(2):sfae409. doi: 10.1093/ckj/sfae409. eCollection 2025 Feb.
citation: Landoni G, Monaco F, Ti LK, Baiardo Redaelli M, Bradic N, Comis M, Kotani Y, Brambillasca C, Garofalo E, Scandroglio AM, Viscido C, Paternoster G, Franco A, Porta S, Ferrod F, Calabro MG, Pisano A, Vendramin I, Barucco G, Federici F, Severi L, Belletti A, Cortegiani A, Bruni A, Galbiati C, Covino A, Baryshnikova E, Giardina G, Venditto M, Kroeller D, Nakhnoukh C, Mantovani L, Silvetti S, Licheri M, Guarracino F, Lobreglio R, Di Prima AL, Fresilli S, Labanca R, Mucchetti M, Lembo R, Losiggio R, Bove T, Ranucci M, Fominskiy E, Longhini F, Zangrillo A, Bellomo R; PROTECTION Study Group. A Randomized Trial of Intravenous Amino Acids for Kidney Protection. N Engl J Med. 2024 Aug 22;391(8):687-698. doi: 10.1056/NEJMoa2403769. Epub 2024 Jun 12.
citation: Baiardo Redaelli M, Monaco F, Bradic N, Scandroglio AM, Ti LK, Belletti A, Viscido C, Licheri M, Guarracino F, Pruna A, Pisano A, Pontillo D, Federici F, Losiggio R, Serena G, Tomasi E, Silvetti S, Ranucci M, Brazzi L, Cortegiani A, Landoni G, Mastroroberto P, Paternoster G, Gaudino MFL, Zangrillo A, Bellomo R; for the PROTECTION Study Group Collaborators. Amino Acid Infusion for Kidney Protection in Cardiac Surgery Patients with Chronic Kidney Disease: A Secondary Analysis of the PROTECTION Trial. Anesthesiology. 2025 May 1;142(5):818-828. doi: 10.1097/ALN.0000000000005336. Epub 2024 Dec 19.