Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery.

NCT03709264 | Completed Phase 3

• 1 other identifier: PROTection/47/OSR
• Study Type: interventional
• Target: 3,511
• Locations: 3 countries
• Sites: 22

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.

Conditions

Cardiac Surgery

Keywords

kidney protection; acute kidney injury; cardiac surgery; amino acids; mortality; ICU

Outcome Measures

Primary Outcomes (1)

• AKI incidence

  Incidence of Acute Kidney Injury during hospital stay

  Until hospital discharge, an average of 10 days

Secondary Outcomes (6)

• Mortality

  180 days

• RRT

  180 days

• ICU stay

  Until ICU discharge, an average of 2 days

• Hospital stay

  Until hospital discharge, an average of 10 days

• Mechanical Ventilation

  Until ICU discharge, an average of 2 days

Study Arms (2)

Amino Acids infusion

EXPERIMENTAL

Drug: Amino Acids

Placebo

PLACEBO COMPARATOR

Drug: Placebos

Interventions

Amino Acids DRUG

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

Amino Acids infusion

Placebos DRUG

Placebo: standard treatment

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age \> 18 years
• scheduled cardiac surgery
• expected to stay in ICU at least 1 night after surgery
• signed informed consent

You may not qualify if:

• 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.

Sponsors & Collaborators

• Università Vita-Salute San Raffaele: lead

Study Sites (22)

University Hospital Dubrava

Dubrava, Croatia

Location

Magdalena Clinic for Cardiovascular Diseases

Zagreb, Croatia

Location

Ospedale San Carlo

Potenza, Basilicate, Italy

Location

Ospedale Mater Domini

Catanzaro, Calabria, Italy

Location

Ospedale Monaldi

Napoli, Campania, Italy

Location

Pineta Grande Hospital

Castel Volturno, Caserta, Italy

Location

Azienda Ospedaliera Sant'Andrea

Rome, Lazio, Italy

Location

Ospedale San Camillo

Rome, Lazio, Italy

Location

IRCCS San Martino Istitute

Genoa, Liguria, Italy

Location

IRCCS Cardiologico Monzino

Milan, Lombardy, 20100, Italy

Location

Istituto Clinico Humanitas

Rozzano, Lombardy, Italy

Location

IRCCS Ospedale San Donato

Miano, Milano, Italy

Location

Città della Salute

Turin, Piedmont, Italy

Location

Ospedale Ordine Mauriziano

Turin, Piedmont, Italy

Location

Maria Cecilia Hospital

Cotignola, Ravenna, Italy

Location

Ospedale del cuore - Fondazione Toscana Gabriele Monasterio

Massa, Tuscany, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

AOU Policlinico Paolo Giaccone

Palermo, Italy

Location

Azienda Ospedaliera Universitaria Pisana

Pisa, Italy

Location

Grande Ospedale Metropolitano

Reggio Calabria, Italy

Location

Ospedale Santa Maria della Misericordia

Udine, Italy

Location

National University Hospital

Singapore, Singapore

Location

Related Publications (13)

• 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. 2025 Aug;120(2):256-266. doi: 10.1016/j.athoracsur.2024.11.020. Epub 2024 Dec 4.

  PMID: 39643100 BACKGROUND

• 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.

  PMID: 39485306 BACKGROUND

• 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.

  PMID: 39384419 BACKGROUND

• 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.

  PMID: 36038001 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 39566002 BACKGROUND

• 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.

  PMID: 39981140 BACKGROUND

• Pruna A, Monaco F, Asiller OO, Delrio S, Yavorovskiy A, Bellomo R, Landoni G. How Would We Prevent Our Own Acute Kidney Injury After Cardiac Surgery? J Cardiothorac Vasc Anesth. 2025 May;39(5):1123-1134. doi: 10.1053/j.jvca.2025.01.019. Epub 2025 Jan 13.

  PMID: 39922732 BACKGROUND

• Bottussi A, D'Andria Ursoleo J, Agosta VT, De Luca M, Monaco F. The role of amino acids and protein administration in preventing cardiac surgery-associated acute kidney injury. Future Cardiol. 2025 Mar;21(3):191-202. doi: 10.1080/14796678.2025.2463271. Epub 2025 Feb 8.

  PMID: 39921856 BACKGROUND

• 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.

  PMID: 38865168 RESULT

• 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.

  PMID: 39705670 RESULT

• Belletti A, Pisano A, Scandroglio AM, Garofalo E, Calabro MG, Ferrod F, Monaco F, Brambillasca C, Baiardo Redaelli M, Meroi F, Fominskiy E, Vignale R, Ajello S, Venditto M, Scquizzato T, Porta S, Losiggio R, Suriano P, Pontillo D, Orso D, Tomasi E, Paternoster G, Lomivorotov V, Longhini F, Landoni G, Zangrillo A, Maisano F, Bellomo R, Pieri M; PROTECTION Study Group Collaborators. Intravenous amino acids for renal protection in patients receiving temporary mechanical circulatory support: a secondary subgroup analysis of the PROTECTION study. Eur J Cardiothorac Surg. 2025 Feb 4;67(2):ezaf035. doi: 10.1093/ejcts/ezaf035.

  PMID: 39977357 RESULT

• Pontillo D, Rong LQ, Pruna A, Pisano A, Monaco F, Bruni A, Baiardo Redaelli M, Ti LK, Belletti A, Bradic N, Massaro C, Barucco G, Viscido C, Losiggio R, Federici F, Marmiere M, Silvetti S, Marchetti C, Carmosino M, Manazza M, Oliva FM, Cortegiani A, Guarracino F, Ranucci M, Paternoster G, Landoni G, Zangrillo A, Gaudino MFL, Bellomo R; PROTECTION Study Group Collaborators. Impact of Cardiopulmonary Bypass Duration on the Renal Effects of Amino Acids Infusion in Cardiac Surgery Patients. J Cardiothorac Vasc Anesth. 2025 Sep;39(9):2296-2306. doi: 10.1053/j.jvca.2025.05.050. Epub 2025 Jun 2.

  PMID: 40571473 RESULT

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Amino Acids

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Associate Professor

Study Record Dates

• First Submitted: October 9, 2018
• First Posted: October 17, 2018
• Study Start: October 7, 2019
• Primary Completion: January 17, 2024
• Study Completion: January 17, 2025
• Last Updated: August 7, 2025

Record last verified: 2025-08

Locations

IT (19); CR (2); SG (1)