Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery.

NCT ID: NCT03709264

Last Updated: 2025-08-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

3511 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-07

Study Completion Date

2025-01-17

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cardiac Surgery

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Amino Acids infusion

Group Type EXPERIMENTAL

Amino Acids

Intervention Type 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

Placebo

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

Placebo: standard treatment

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Amino Acids

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

Intervention Type DRUG

Placebos

Placebo: standard treatment

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Università Vita-Salute San Raffaele

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Giovanni Landoni

MD, Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University Hospital Dubrava

Dubrava, , Croatia

Site Status

Magdalena Clinic for Cardiovascular Diseases

Zagreb, , Croatia

Site Status

Ospedale San Carlo

Potenza, Basilicate, Italy

Site Status

Ospedale Mater Domini

Catanzaro, Calabria, Italy

Site Status

Ospedale Monaldi

Napoli, Campania, Italy

Site Status

Pineta Grande Hospital

Castel Volturno, Caserta, Italy

Site Status

Azienda Ospedaliera Sant'Andrea

Rome, Lazio, Italy

Site Status

Ospedale San Camillo

Rome, Lazio, Italy

Site Status

IRCCS San Martino Istitute

Genoa, Liguria, Italy

Site Status

IRCCS Cardiologico Monzino

Milan, Lombardy, Italy

Site Status

Istituto Clinico Humanitas

Rozzano, Lombardy, Italy

Site Status

IRCCS Ospedale San Donato

Miano, Milano, Italy

Site Status

Città della Salute

Turin, Piedmont, Italy

Site Status

Ospedale Ordine Mauriziano

Turin, Piedmont, Italy

Site Status

Maria Cecilia Hospital

Cotignola, Ravenna, Italy

Site Status

Ospedale del cuore - Fondazione Toscana Gabriele Monasterio

Massa, Tuscany, Italy

Site Status

Ospedale San Raffaele

Milan, , Italy

Site Status

AOU Policlinico Paolo Giaccone

Palermo, , Italy

Site Status

Azienda Ospedaliera Universitaria Pisana

Pisa, , Italy

Site Status

Grande Ospedale Metropolitano

Reggio Calabria, , Italy

Site Status

Ospedale Santa Maria della Misericordia

Udine, , Italy

Site Status

National University Hospital

Singapore, , Singapore

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Croatia Italy Singapore

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 39643100 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 39485306 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 39384419 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36038001 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 39566002 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 39981140 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 39922732 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 39921856 (View on PubMed)

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.

Reference Type RESULT
PMID: 38865168 (View on PubMed)

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.

Reference Type RESULT
PMID: 39705670 (View on PubMed)

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.

Reference Type RESULT
PMID: 39977357 (View on PubMed)

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.

Reference Type RESULT
PMID: 40571473 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

PROTection/47/OSR

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Heme Arginate in Cardiac Surgery Patients
NCT02142699 COMPLETED PHASE2