Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery.

Cardiac Surgery Clinical Trial

— PROTection  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03709264
• Other study ID #: PROTection/47/OSR
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 7, 2019
• Est. completion date: July 2024

Study information

• Verified date: April 2024
• Source: Università Vita-Salute San Raffaele
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 3511
• Est. completion date: July 2024
• Est. primary completion date: January 17, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiac Surgery

Intervention

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
• Placebos
Placebo: standard treatment

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Università Vita-Salute San Raffaele

Countries where clinical trial is conducted

Croatia,  Italy,  Singapore, 

References & Publications (3)

Doig GS, Simpson F, Bellomo R, Heighes PT, Sweetman EA, Chesher D, Pollock C, Davies A, Botha J, Harrigan P, Reade MC. Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial. Intensive Care Med. 2015 Jul;41(7):1197-208. doi: 10.1007/s00134-015-3827-9. Epub 2015 Apr 30. — View Citation

Robert AM, Kramer RS, Dacey LJ, Charlesworth DC, Leavitt BJ, Helm RE, Hernandez F, Sardella GL, Frumiento C, Likosky DS, Brown JR; Northern New England Cardiovascular Disease Study Group. Cardiac surgery-associated acute kidney injury: a comparison of two consensus criteria. Ann Thorac Surg. 2010 Dec;90(6):1939-43. doi: 10.1016/j.athoracsur.2010.08.018. — View Citation

Thiele RH, Isbell JM, Rosner MH. AKI associated with cardiac surgery. Clin J Am Soc Nephrol. 2015 Mar 6;10(3):500-14. doi: 10.2215/CJN.07830814. Epub 2014 Nov 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AKI incidence	Incidence of Acute Kidney Injury during hospital stay	Until hospital discharge, an average of 10 days
Secondary	Mortality	All-cause mortality at ICU discharge, hospital discharge, 30 and 90 and 180 days after randomization	180 days
Secondary	RRT	Need and duration of renal replacement therapy	180 days
Secondary	ICU stay	Duration of Intensive Care Unit stay	Until ICU discharge, an average of 2 days
Secondary	Hospital stay	Duration of hospital stay	Until hospital discharge, an average of 10 days
Secondary	Mechanical Ventilation	Need and duration of mechanical ventilation	Until ICU discharge, an average of 2 days
Secondary	EQ-5D	Quality of life at 180 days after randomization as measured by the EQ-5D	180 days