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Cardiac SurgeryPhase 3PROTectionNCT03709264

Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery.

A Phase 3 study testing Amino Acids in people with Cardiac Surgery, run by Università Vita-Salute San Raffaele at 22 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cardiac Surgery
What is being tested?
Amino Acids
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
3,511 participants
Where
22 sitesin 3 countries
Study dates
7 Oct 2019to 17 Jan 2025
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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
Show all 11Show fewer
  • 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.

Trial locations and contacts

22 sites in 3 countries.

22 sites in 3 countries

Italy19 sites
  • Pineta Grande Hospital

    Castel Volturno, Caserta

  • Ospedale Mater Domini

    Catanzaro, Calabria

  • Maria Cecilia Hospital

    Cotignola, Ravenna

  • IRCCS San Martino Istitute

    Genoa, Liguria

  • Ospedale del cuore - Fondazione Toscana Gabriele Monasterio

    Massa, Tuscany

  • IRCCS Ospedale San Donato

    Miano, Milano

  • IRCCS Cardiologico Monzino

    Milan, Lombardy, 20100

  • Ospedale San Raffaele

    Milan, 20132

  • Ospedale Monaldi

    Naples, Campania

  • AOU Policlinico Paolo Giaccone

    Palermo

  • Azienda Ospedaliera Universitaria Pisana

    Pisa

  • Ospedale San Carlo

    Potenza, Basilicate

  • Grande Ospedale Metropolitano

    Reggio Calabria

  • Azienda Ospedaliera Sant'Andrea

    Rome, Lazio

  • Ospedale San Camillo

    Rome, Lazio

  • Istituto Clinico Humanitas

    Rozzano, Lombardy

  • Città della Salute

    Turin, Piedmont

  • Ospedale Ordine Mauriziano

    Turin, Piedmont

  • Ospedale Santa Maria della Misericordia

    Udine

Other trials in Italy

Croatia2 sites
  • University Hospital Dubrava

    Dubrava

  • Magdalena Clinic for Cardiovascular Diseases

    Zagreb

Other trials in Croatia

Singapore1 site
  • National University Hospital

    Singapore

Other trials in Singapore

About this study

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

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
Being tested
Amino Acids, Placebos
Keywords
kidney protection, acute kidney injury, cardiac surgery, amino acids, mortality, ICU
Medical subject headings
Acute Kidney Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Amino AcidsDrug

    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

  • PlacebosDrug

    Placebo: standard treatment

Study groups in NCT03709264
Study groupRoleWhat they receive
Amino Acids infusionExperimentalNot described
Receives: Drug: Amino Acids
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebos

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. AKI incidence

    Incidence of Acute Kidney Injury during hospital stay

    Measured: Until hospital discharge, an average of 10 days

Secondary outcomes (6)
  1. Mortality

    All-cause mortality at ICU discharge, hospital discharge, 30 and 90 and 180 days after randomization

    Measured: 180 days

  2. RRT

    Need and duration of renal replacement therapy

    Measured: 180 days

  3. ICU stay

    Duration of Intensive Care Unit stay

    Measured: Until ICU discharge, an average of 2 days

  4. Hospital stay

    Duration of hospital stay

    Measured: Until hospital discharge, an average of 10 days

  5. Mechanical Ventilation

    Need and duration of mechanical ventilation

    Measured: Until ICU discharge, an average of 2 days

  6. EQ-5D

    Quality of life at 180 days after randomization as measured by the EQ-5D

    Measured: 180 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Oct 2018
  2. Study start7 Oct 2019
  3. Primary completion17 Jan 2024
  4. Study completion17 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
3,511 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03709264
Sponsor's protocol ID
PROTection/47/OSR
Acronym
PROTection
Status last verified
Aug 2025
First submitted
9 Oct 2018
Last updated
7 Aug 2025
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 39643100
  • 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.

    PubMed 39485306
  • 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.

    PubMed 39384419
  • 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.

    PubMed 36038001
  • 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.

  • 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.

    PubMed 39566002
  • 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.

    PubMed 39981140
  • 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.

    PubMed 39922732
  • 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.

    PubMed 39921856
  • 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.

    PubMed 38865168
  • 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.

    PubMed 39705670
  • 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.

    PubMed 39977357
  • 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.

    PubMed 40571473
  • Landoni G, Oriani A, Ti LK, Losiggio R, Bradic N, Pruna A, Burrell A, Pieri M, Hodgson CL, D'Amico F, Ranucci M, Oliva FM, Comis M, Calabro MG, Viscido C, Ajello S, Ferrod F, Fresilli S, Guarracino F, Damiani D, Pisano A, Bonizzoni MA, Silvetti S, Pontillo D, Neri G, Scquizzato T, Bosco V, Marmiere M, Carmosino M, Labanca R, Federici F, Giardina G, Baiardo Redaelli M, Belletti A, Costamagna A, Fominskiy E, Arangino C, Scandroglio AM, Monti G, Cortegiani A, Paternoster G, Bove T, Bellomo R, Zangrillo A, Monaco F; PROTECTION Study Group Collaborators. Association of duration of amino acids infusion and renal protection: a secondary analysis of the PROTECTION trial. Br J Anaesth. 2026 Jul;137(1):110-117. doi: 10.1016/j.bja.2025.12.054. Epub 2026 Feb 24.

    PubMed 41741282
  • Consonni M, Fresilli S, Kotani Y, Garofalo E, Bradic N, Scandroglio AM, Ti LK, Comis M, Oriani A, Pisano A, Belletti A, Guarracino F, Losiggio R, Redaelli MB, Pontillo D, Arangino C, Pruna A, Federici F, D'Amico F, Silvetti S, Labanca R, Ferrod F, Pittella G, Corbo F, Ranucci M, Cortegiani A, Paternoster G, Bove T, Longhini F, Monaco F, Zangrillo A, Piemonti L; PROTECTION Study Group Collaborators. Diabetes does not modify the renal-protective effect of intravenous amino acids infusion after cardiac surgery. J Endocrinol Invest. 2026 May;49(5):1163-1172. doi: 10.1007/s40618-025-02804-0. Epub 2026 Jan 9.

    PubMed 41511746

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Amino Acids in people with Cardiac Surgery, run by Università Vita-Salute San Raffaele at 22 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Italy, Croatia, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AKI incidence (time frame: Until hospital discharge, an average of 10 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03709264, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2025.

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