The AminoECMO Pilot Trial (AminoECMO)

A Pilot, Three-centre, Placebo Controlled, Physiology and Feasibility Randomised Controlled Trial of Intravenous Amino Acid Therapy in ECMO Dependent Adults Admitted to the Intensive Care Unit

Acute kidney injury (AKI) is a serious problem for patients in intensive care, especially those on life-support machines like ECMO (which helps the heart and lungs). More than half of these patients develop severe kidney problems that often require dialysis, and this greatly increases the risk of poor outcomes.

Doctors try to prevent AKI by treating the underlying illness, avoiding kidney-harming drugs, and carefully managing fluids. But these methods are mostly supportive - they don't actively improve kidney function.

Studies in surgical patients (especially heart and urology operations) show that giving amino acids before surgery can reduce the chance of developing AKI. A major clinical trial even found that this approach significantly lowered AKI rates in heart surgery patients.

Amino acids (the building blocks of protein) seem to boost kidney performance. When given through a drip or feeding tube, they increase blood flow to the kidneys and may "wake up" unused kidney capacity - a concept called "functional renal reserve." It's not yet clear whether amino acids help critically ill patients on ECMO. More research is needed to see if this promising strategy can improve kidney function and outcomes in the sickest patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Dietary supplement: Synthamin-17 (10% amino acid solution); Other: Placebo (Hartmann's balanced crystalloid solution)

Detailed Description

Acute kidney injury (AKI) is common in critically ill patients, especially in those requiring extracorporeal membrane oxygenation (ECMO). AKI is associated with significant morbidity and mortality. The current management for the prevention of AKI is supportive, such as treating underlying causes, avoiding nephrotoxins, and optimising fluid status. Despite optimal care, more than half of ECMO patients develop severe AKI requiring renal replacement therapy (RRT), including 46% in venovenous (V-V) ECMO, and 61% in venoarterial (V-A) ECMO. Severe AKI is associated with significantly worse outcomes and higher mortality, and there is a strong need to identify therapies that can improve renal function in ECMO.

It has already been established that glomerular filtration rate (GFR) increases in response to (IV or enteral) protein administration. The precise mechanism for increased GFR is not completely understood, however recruitment of dormant renal function (called functional renal reserve RFR) has been hypothesised. Amino acid delivery is associated with a renal vasodilation mediated increase renal blood flow by >30%. Different metabolic, endocrine, and paracrine factors have been implicated. It has been suggested that recruitment of RFR could prevent or manage AKI.

Amino Acids Infusions and Preventing AKI The impact of amino acids on renal function has been investigated in clinical trials. This has predominantly occurred in the perioperative setting, in patients with stable renal function undergoing operations associated with a significant risk of developing an AKI. In cardiac surgery, several early-phase studies have demonstrated an improvement in measures of renal function with the perioperative infusion of amino acids. These findings are not isolated to the cardiac surgery population, which may have unique pathological mechanisms for AKI, as a recent pilot RCT in patients undergoing major urology surgery demonstrated a reduction in the incidence of postoperative AKI. Recently a large RCT published in the New England Journal of Medicine showed that the peri-operative administration of amino acids in patients undergoing cardiac surgery significantly decreased the incidence of AKI. Importantly, in a sub group analysis of 232 patients who underwent perioperative mechanical cardiac support, the rate of AKI was lower in the group randomized to amino acids: 44.6 vs 60.8% relative risk 0.73 (0.57-0.94 P=0.01 NNT =6) suggesting a potentially important benefit in this group.

Despite the increasing interest and quantity of research surrounding the association between amino acid infusion and kidney function, several unanswered questions remain. Firstly, although amino acid infusion has been demonstrated to reduce the incidence of AKI when administered before an insult, the impact on renal function in critically ill patients receiving ECMO therapy is unclear, particularly as the insult may have already started to occur prior to ECMO initiation. Secondly, several recent studies of high dose protein have suggested potential harm in patients randomised to a higher dose of protein (2.2g/kg/day vs <1.2g/kg/day) when given over prolonged periods.

The intervention in this pilot differs as it is will commence <24hours post ECMO initiation, and it is given short term only (up to 48 hours). It remains unclear if this will translate to improve renal and patient outcomes.

In summary, ECMO therapy is associated with an increased risk of acute kidney injury. The current management for prevention of AKI is supportive with no current therapies that can decrease the risk of AKI and improve clinical outcomes. Given the physiologically and clinically demonstratable impact of amino acid infusion on renal function, further research is logical and desirable.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Aidan Burrell, MBBS, FCICM, DDU, PhD; Phone Number: +61 422 848 716; Email: aidanburrell@gmail.com
• Study Contact Backup: Name: Stephanie M Hunter, BN, PhD; Phone Number: +61 422 033 612; Email: Stephanie.Hunter@monash.edu

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
      • Contact: Andrew Udy, BHB, MB ChB, PGCert (AME) PhD; Phone Number: +61 03 9076 8347; Email: A.Udy@alfred.org.au
      • Contact: Emma-Leah Martin; Phone Number: +61 03 9076 8347

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged ≥18 years
• Enrolled in the EXCEL Registry

Exclusion Criteria:

• Urea level ≥30 mmol/L
• Requirement for renal replacement therapy
• Chronic hemodialysis or peritoneal dialysis
• ECMO for ≥24 hours
• Pre-admission CKD with an eGFR <30 ml/min
• Previous enrolment in this study
• Pregnant or Lactating
• Known contraindication to AA infusion
• ECMO expected to cease ≤24 hours
• Expected to be transferred to another hospital ≤24 hours
• Treating clinical team deems study is not in the patient's best interest

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention Arm - Synthamin-17 electrolyte-free solution; The study drug within the intervention arm will be continually infused for up to 48 hours whilst the patient is on ECMO. The infusion rate will be set to 2g/kg/ideal body weight/day (to a maximum of 100g). Patients enrolled into the control arm will be continually infused with a placebo for up to 48 hours whilst on ECMO.	Dietary supplement: Synthamin-17 (10% amino acid solution); First time comparing amino acid to placebo for prevention of acute kidney injury in patients receiving extracorporeal membrane oxygenation
Placebo Comparator: Control Arm - Hartmann's balanced crystalloid solution; Participants allocated to the control group will receive placebo comprised of Hartmann's balanced crystalloid solution (compound sodium lactate) to a maximum of 500mls and 48-hours.	Other: Placebo (Hartmann's balanced crystalloid solution); Participants allocated to the control group will receive placebo comprised of Hartmann's balanced crystalloid solution (compound sodium lactate) to a maximum of 500mls and 48-hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of patients who received AA infusion within 24 hours of being randomised in the trial after ECMO initiation.	Participants randomised to the Intervention Group who received AA infusion within the 24 hour study time frame.	24 Hours from randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of hours post randomisation that AA infusion was commenced in the intervention group	Date and time of randomisation and date and time that AA infusion was commenced	Up to 24 hours post randomisation, or will be recorded as a Protocol Deviation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients who received AA infusion in the Intervention Group	The total number of participants randomised to the Intervention Group who received AA infusion	Up to 48 hours from randomisation
Number of patients who received placebo in the control group	The number of participants randomised to the Control Group who received placebo	Up to 48 hours post randomisation
Mean duration of AA infusion	What was the mean duration of AA infusion in participants who received it?	Up to 48 hours post randomisation
Enrolment Rate	How many participants were enrolled in the trial from the eligible population?	Up to 7 days from commencement of ECMO
Number of Protocol Deviations	How many total Protocol Deviations were recorded?	Up to 7 days post commencement of ECMO
Mortality - in ICU and in hospital	Patients who died before being discharged from ICU or Hospital	Participants discharge from ICU and Hospital
Urine output measured over 48 hours post the start of the AA or placebo infusion	Hourly urine output measures	From initiation of AA or placebo infusion
Serum creatinine measured over 48 hours post the start of the AA and placebo infusion	Serum creatinine measures from bloods taken at specified times	Blood sampling at Baseline, Day 1, Day 3, and Day 7
Urinary Neutrophil Gelatinase-associated lipocalin (NGAL) measured over 48 hours post the start of the AA and placebo infusion	Urinary NGAL processed from urine samples at pre-specified times	Urine sampling taken at Baseline, Day 1, Day 3, and Day 7
Urine albumin/creatinine ratio (ACR) measured over 48 hours post the start of the AA and placebo infusion	ACR processed from urine samples collected at pre-specified times	Urine sampling at Baseline, Day 1, Day 3, and Day 7
Urinary electrolytes measured over 48 hours post the start of the AA and placebo infusion	Urinary electrolytes processed from samples taken at pre-specified times	Urine sampling at Baseline, Day 1, Day 3, and Day 7
Maximum severity of AKI up to day 7 (defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria)	The KDIGO will be assessed from serum creatinine and urine output	Assessed at Day 1, Day 3, and Day 7 from randomisation
Duration of Acute Kidney Injury (AKI)	If AKI is present how long does it persist?	Up to Day 30 post randomisation
Occurrence of acute kidney disease (AKD) (defined by the Acute Dialysis Quality Initiative - ADQI criteria)	Calculation of ADQI from serum creatinine, urine output and glomerular filtration rate	Up to Day 7 from randomisation
New onset renal replacement therapy (RRT) during ECMO	Was RRT commenced for AKI while participant was receiving ECMO?	From randomisation to cessation of ECMO flow

Collaborators and Investigators

• Sponsor: Australian and New Zealand Intensive Care Research Centre
• Collaborators: Monash University; The Alfred
• Investigators: Study Chair: Carol Hodgson, FAHMS, Monash University, School of Public Health and Preventative Medicine, ANZIC-RC

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: February 3, 2026
• First Submitted That Met QC Criteria: February 22, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 22, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Acute kidney injury; Extracorporeal Membrane Oxygenation; Amino Acids
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: ANZIC-RC/AB0004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The management committee support the view of the international committee of medical journal editors and the world health organisation (WHO) with reference to the ethical obligation to responsibly share data acquired by interventional clinical trials. At the conclusion of the study, the management committee will consider requests from researchers who provide a methodically sound confidential scientific proposal as per the data sharing policy set out in the ANZIC-RC terms of reference. Only de-identified data will be shared and all requests for data must comply with the ethical, regulatory, and legislative requirements governing their jurisdiction.
• IPD Sharing Time Frame: Supporting information will be available from October 2026, and there will be no specified end date that this information can be accessed.
• IPD Sharing Access Criteria: The Study Protocol and Statistical Analysis Plan will both be available on the Monash ANZIC-RC site from October 2026 onward.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No