Ultrasound Markers of Organ Congestion in Severe Acute Kidney Injury (ECHO-AKI)

• ClinicalTrials.gov Identifier: NCT04095143
• Recruitment Status: Completed
• First Posted: September 19, 2019
• Last Update Posted: November 14, 2022
• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: Unity Health Toronto; Sunnybrook Health Sciences Centre; University of Kentucky; University of Alberta; Montreal Heart Institute
• Information provided by (Responsible Party): Centre hospitalier de l'Université de Montréal (CHUM)

Tracking Information

• First Submitted Date: September 17, 2019
• First Posted Date: September 19, 2019
• Last Update Posted Date: November 14, 2022
• Actual Study Start Date: September 4, 2018
• Actual Primary Completion Date: January 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 19, 2019)

Number of participants with major adverse kidney events at 30 days [ Time Frame: 30 days ]

Either death, receipt of renal replacement therapy or sustained loss of kidney function (new onset of estimated glomerular filtration rate (eGFR) < 60 or, if pre-existing eGFR < 60, 25% or greater decline in eGFR)

Original Primary Outcome Measures (submitted: September 17, 2019)

Major adverse kidney events at 30 days [ Time Frame: 30 days ]

Either death, receipt of renal replacement therapy or sustained loss of kidney function (new onset of estimated glomerular filtration rate (eGFR) < 60 or, if pre-existing eGFR < 60, 25% or greater decline in eGFR)

Current Secondary Outcome Measures (submitted: September 19, 2019)

• Rate of in-hospital death [ Time Frame: 30 days ]
  All cause mortality during hospital stay
• Number of participants with renal replacement therapy dependence at 30 days [ Time Frame: 30 days ]
  Receipt of renal replacement therapy at 30 days from enrollment
• Number of participants with sustained loss of kidney function at 30 days [ Time Frame: 30 days ]
  New onset of estimated glomerular filtration rate (eGFR) < 60 or, if pre-existing eGFR < 60, 25% or greater decline in eGFR)
• Ventilation-free days through day 30 [ Time Frame: 30 days ]
  A ventilator-free day will be defined as the receipt of < 2 hours of either invasive or non-invasive ventilation within a 24-hour period.
• Intensive care unit (ICU)-free days through day 30 [ Time Frame: 30 days ]
  An ICU-free day will be defined as admission to an ICU for < 2 hours within a 24 hours period.
• Vasopressor-free days though day 30 [ Time Frame: 30 days ]
  Vasopressor will include norepinephrine, epinephrine, vasopressin and phenylephrin
• Number of participants with major adverse kidney events at 90 days [ Time Frame: 90 days ]
  Either death, receipt of renal replacement therapy or sustained loss of kidney function (estimated glomerular filtration rate (eGFR) < 60 or, if pre-existing eGFR < 60, 25% or greater decline in eGFR)
• Rate of death at 90 days [ Time Frame: 90 days ]
  All cause mortality at 90 days
• Estimated glomerular filtration rate at 90 days [ Time Frame: 90 days ]
  Calculated with the CKD-EPI equation (92) with serum creatinine from a sample drawn as close as possible to Day 90.

Original Secondary Outcome Measures (submitted: September 17, 2019)

• In-hospital death [ Time Frame: 30 days ]
  All cause mortality during hospital stay
• Renal replacement therapy dependence at 30 days [ Time Frame: 30 days ]
  Receipt of renal replacement therapy at 30 days from enrollment
• Sustained loss of kidney function at 30 days [ Time Frame: 30 days ]
  New onset of estimated glomerular filtration rate (eGFR) < 60 or, if pre-existing eGFR < 60, 25% or greater decline in eGFR)
• Mechanical ventilation-free days through day 30 [ Time Frame: 30 days ]
  A ventilator-free day will be defined as the receipt of < 2 hours of either invasive or non-invasive ventilation within a 24-hour period.
• Intensive care unit (ICU)-free days through day 30 [ Time Frame: 30 days ]
  An ICU-free day will be defined as admission to an ICU for < 2 hours within a 24 hours period.
• Vasopressor-free days though day 30 [ Time Frame: 30 days ]
  Vasopressor will include norepinephrine, epinephrine, vasopressin and phenylephrin
• Major adverse kidney events at 90 days [ Time Frame: 90 days ]
  Either death, receipt of renal replacement therapy or sustained loss of kidney function (estimated glomerular filtration rate (eGFR) < 60 or, if pre-existing eGFR < 60, 25% or greater decline in eGFR)
• Death at 90 days [ Time Frame: 90 days ]
  All cause mortality at 90 days
• Estimated glomerular filtration rate at 90 days [ Time Frame: 90 days ]
  Calculated with the CKD-EPI equation (92) with serum creatinine from a sample drawn as close as possible to Day 90.

Current Other Pre-specified Outcome Measures (submitted: September 17, 2019)

Hemodynamic instability during renal replacement therapy [ Time Frame: 7 days ]

Intradialytic hypotension (MAP<65 mmHg) requiring one or more of the following interventions: interruption of fluid removal, introduction of norepinephrine or increase in its dose of more than 25%, administration of volume expansion or interruption of RRT within 8 hours after initiating net negative fluid balance.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Ultrasound Markers of Organ Congestion in Severe Acute Kidney Injury
• Official Title: Ultrasound Markers of Organ Congestion in Severe Acute Kidney Injury
• Brief Summary: Fluid overload is associated with adverse outcomes in patients with severe acute kidney injury. It remains unclear if fluid overload is merely a marker of disease severity or if organ congestion is a mediator of complications. Point-of-care ultrasound could be a modality used to assess organ congestion and its clinical implications. The objective of this study is to determine whether ultrasound markers of organ congestion are associated with major adverse kidney events in critically ill patients with severe acute kidney injury.

Detailed Description

Background: Fluid overload is associated with adverse outcomes in patients with severe acute kidney injury. It remains unclear if fluid overload is merely a marker of disease severity or if organ congestion is a direct mediator of complications. Point-of-care ultrasound could be a modality used to assess organ congestion and its clinical implications.

Objective: To determine whether ultrasound markers of organ congestions are associated with major adverse kidney events and other adverse clinical outcomes.

Study design: A cohort of critically ill patients with a new onset of severe acute kidney injury will undergo repeated ultrasound assessments to detect the presence of the following markers:

• Portal flow pulsatility on pulse-wave Doppler
• Discontinuous intra-renal venous flow on pulse-wave Doppler
• Abnormal hepatic vein waveform on pulse wave Doppler
• Presence of pulmonary B-line artifacts on 2D lung ultrasound
• Presence of dilated and non-collapsible inferior vena cava on 2D ultrasound
• Presence of systolic right ventricular dysfunction
• Presence of systolic left ventricular dysfunction

Clinical outcomes will be collected for up to 90 days after recruitment.

Perspective: An approach targeting the resolution of organ congestion might improve the prognosis in patients with severe acute kidney injury. Identifying clinically relevant markers of organ congestion is a precursor to the design of future interventional trials investigating personalized fluid balance management.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Critically ill adult patients with severe acute kidney injury

Condition

• Acute Kidney Injury
• Fluid Overload
• Ultrasonography

Intervention

• Diagnostic Test: Portal vein flow
  Doppler assessment performed on day 0, 3 and 7.
• Diagnostic Test: Intra-renal flow
  Doppler assessment performed on day 0, 3 and 7.
• Diagnostic Test: Hepatic vein flow
  Doppler assessment performed on day 0, 3 and 7.
• Diagnostic Test: Pulmonary B-lines
  Ultrasound assessment of performed on day 0, 3 and 7.
• Diagnostic Test: Dimensions of the inferior vena cava
  Ultrasound assessment of performed on day 0, 3 and 7.
• Diagnostic Test: Left ventricular function
  Ultrasound assessment of performed on day 0, 3 and 7.
• Diagnostic Test: Right ventricular function
  Ultrasound assessment of performed on day 0, 3 and 7.

Study Groups/Cohorts

New onset of stage ≥2 acute kidney injury

Either:

1. A ≥ 2-fold increase in serum creatinine OR
2. A serum creatinine ≥ 354 μmol/L with evidence of a minimum increase of 27 μmol/L OR
3. Urine output < 6.0 mL/kg over the preceding 12 hours OR
4. Initiation of RRT for severe acute kidney injury less than 72 hours before recruitment

Interventions:

• Diagnostic Test: Portal vein flow
• Diagnostic Test: Intra-renal flow
• Diagnostic Test: Hepatic vein flow
• Diagnostic Test: Pulmonary B-lines
• Diagnostic Test: Dimensions of the inferior vena cava
• Diagnostic Test: Left ventricular function
• Diagnostic Test: Right ventricular function

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 11, 2022): 125
• Original Estimated Enrollment (submitted: September 17, 2019): 130
• Actual Study Completion Date: September 1, 2022
• Actual Primary Completion Date: January 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≥ 18 years
• Admitted to the ICU
• Women with serum creatinine ≥ 100 µmol/L and men with serum creatinine ≥ 130 µmol/L
• Severe acute kidney injury (AKI) defined either: A ≥ 2-fold increase in serum creatinine from a known pre-morbid baseline or during the current hospitalization OR achievement of a serum creatinine ≥ 354 µmol/L with evidence of a minimum increase of 27 µmol/L from pre-morbid baseline or during the current hospitalization OR Urine output < 6.0 mL/kg over the preceding 12 hours OR initiation of renal replacement therapy (RRT) for severe AKI initiated less than 72 hours before recruitment.

Exclusion Criteria:

• Lack of commitment to provide RRT as part of limitation of ongoing life support. (Operational definition: Critical care team has deemed the patient not to be eligible for escalation of life support, including the initiation of RRT, or substitute decision makers have declined offer of same.)
• Known pre-hospitalization advanced chronic kidney disease, defined by an estimated glomerular filtration rate < 20 mL/min/1.73 m2 in a patient who is not on chronic RRT. (Operational definition: The coordinator will review all documented serum creatinine values within 365 days prior to the date of admission for the current hospitalization. The value closest to the admission date will be considered as the "baseline" and will be used to calculate the corresponding estimated glomerular filtration rate using an online calculator. A value of < 20 mL/min/1.73 m2 derived from the CKD-EPI equation will be grounds for exclusion.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT04095143
• Other Study ID Numbers: MP-02-2020-8578 (MP)
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Centre hospitalier de l'Université de Montréal (CHUM)
• Original Responsible Party: Same as current
• Current Study Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Original Study Sponsor: Same as current

Collaborators

• Unity Health Toronto
• Sunnybrook Health Sciences Centre
• University of Kentucky
• University of Alberta
• Montreal Heart Institute

Investigators

• Principal Investigator: William Beaubien-Souligny, MD; CHUM

• PRS Account: Centre hospitalier de l'Université de Montréal (CHUM)
• Verification Date: November 2022