Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery. (PROTection)

August 5, 2025 updated by: Giovanni Landoni, Università Vita-Salute San Raffaele

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

3511

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Croatia
      • Dubrava, Croatia
        • University Hospital Dubrava
      • Zagreb, Croatia
        • Magdalena Clinic for Cardiovascular Diseases
  • Italy
      • Milano, Italy, 20132
        • Ospedale San Raffaele
      • Palermo, Italy
        • AOU Policlinico Paolo Giaccone
      • Pisa, Italy
        • Azienda Ospedaliera Universitaria Pisana
      • Reggio Calabria, Italy
        • Grande Ospedale Metropolitano
      • Udine, Italy
        • Ospedale Santa Maria Della Misericordia
    • Basilicata
      • Potenza, Basilicata, Italy
        • Ospedale San Carlo
    • Calabria
      • Catanzaro, Calabria, Italy
        • Ospedale Mater Domini
    • Campania
      • Napoli, Campania, Italy
        • Ospedale Monaldi
    • Caserta
      • Castel Volturno, Caserta, Italy
        • Pineta Grande Hospital
    • Lazio
      • Roma, Lazio, Italy
        • Azienda Ospedaliera Sant'Andrea
      • Roma, Lazio, Italy
        • Ospedale San Camillo
    • Liguria
      • Genova, Liguria, Italy
        • IRCCS San Martino Istitute
    • Lombardy
      • Milano, Lombardy, Italy, 20100
        • IRCCS Cardiologico Monzino
      • Rozzano, Lombardy, Italy
        • Istituto Clinico Humanitas
    • Milano
      • Miano, Milano, Italy
        • IRCCS Ospedale San Donato
    • Piemonte
      • Torino, Piemonte, Italy
        • Città della Salute
      • Torino, Piemonte, Italy
        • Ospedale Ordine Mauriziano
    • Ravenna
      • Cotignola, Ravenna, Italy
        • Maria Cecilia Hospital
    • Toscana
      • Massa, Toscana, Italy
        • Ospedale del cuore - Fondazione Toscana Gabriele Monasterio
  • Singapore
      • Singapore, Singapore
        • National University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebos
Placebo: standard treatment
Experimental: Amino Acids infusion
Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AKI incidence
Time Frame: Until hospital discharge, an average of 10 days
Incidence of Acute Kidney Injury during hospital stay
Until hospital discharge, an average of 10 days

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Università Vita-Salute San Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 7, 2019

Primary Completion (Actual)

January 17, 2024

Study Completion (Actual)

January 17, 2025

Study Registration Dates

First Submitted

October 9, 2018

First Submitted That Met QC Criteria

October 15, 2018

First Posted (Actual)

October 17, 2018

Study Record Updates

Last Update Posted (Actual)

August 7, 2025

Last Update Submitted That Met QC Criteria

August 5, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • PROTection/47/OSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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