Albumin To Enhance Recovery After Acute Kidney Injury

Phase 4

Recruiting

• Conditions: Renal Replacement Therapy; Acute Kidney Injury; Critical Illness; Hypotension
• Interventions: Other: 0.9% Normal Saline (100 mL); Biological: 20-25% Albumin fluid (100 mL)

• Registration Number: NCT04705896
• Lead Sponsor: Ottawa Hospital Research Institute

Brief Summary

Study objectives:

To determine whether, in critically ill patients with Acute Kidney Injury requiring renal replacement therapy (AKI-RRT), randomization to receive intravenous hyperoncotic albumin 20-25% (100 mL X two doses) compared to control/placebo normal saline boluses (100 mL X two doses) given during RRT sessions, leads to:

1. An increase in organ support-free days (primary outcome) at 28 days following randomization; and

2. An increase in RRT-free days (principal secondary outcome) at 28 days following randomization.

Detailed Description

Background: Severe Acute Kidney Injury that necessitates renal replacement therapy (AKI-RRT) is a frequent complication of critical illness and portends severe outcomes: high morbidity, an approximately 50% risk of in-hospital death, and increased healthcare resource utilization. Although life-saving when needed, RRT itself may contribute to the poor outcomes associated with AKI-RRT. Since RRT treatments frequently cause hypotension, repeated episodes of kidney and other organ ischemia may occur during RRT. Hypotension during RRT is often triggered by fluid removal. At the same time, there is some evidence that more aggressive ultrafiltration could be beneficial in AKI-RRT.

Albumin is a protein that is the primary contributor to the colloid oncotic pressure maintaining the effective circulating volume (ECV) during RRT. Critically ill patients with AKI-RRT are nearly always hypoalbuminemic. Despite its high cost and limited evidence to support the practice, intravenous hyperoncotic albumin is commonly administered to patients with AKI-RRT in an effort to boost the colloid oncotic pressure and maintain the blood pressure while simultaneously facilitating fluid removal

Objective:

This proposed trial is intended to provide definitive evidence as to the efficacy of a frequently used and expensive intervention to promote hemodynamic stability and augment ultrafiltration during RRT in critically ill patients

Design: A randomized controlled trial with two parallel arms. Setting: The mixed medical-surgical intensive care units of five Canadian tertiary care hospitals with plans to expand to include other centres across Canada and internationally.

Study Population: 856 patients admitted to the Intensive Care Unit (ICU) with AKI requiring treatment with RRT .

Intervention: Participants will be randomized 1:1 to receive either albumin (20-25%) boluses or normal saline placebo boluses at the start and halfway through RRT sessions in ICU, during their RRT treatments to a maximum of 14 days.

Study Timeline

• Study First Submitted: 2021-01-07
• Study First Submitted QC: 2021-01-09
• Study First Posted: 2021-01-12
• Study Start: 2023-11-02
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-30
• Last Update Posted: 2025-05-01
• Primary Completion: 2025-08-28
• Study Completion: 2025-10-23

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 856

Inclusion Criteria

• Age ≥18 years old;
• Admission to a critical care unit/intensive care unit (ICU) for > 24 hours;
• Receiving vasoactive therapy AND/OR undergoing mechanical ventilation (including non-invasive mechanical ventilation (NIMV));
• Immediate initiation of RRT for management of AKI is planned OR additional RRT sessions are imminently planned for patients who already received RRT during their ICU admission;

Exclusion Criteria

• Initiation of RRT for reasons other than AKI (e.g. drug intoxication, hypothermia) ;

• Known pre-hospitalization end-stage kidney disease;

• Kidney transplant within the past 365 days;

• Presence or clinical suspicion of renal obstruction, rapidly progressive glomerulonephritis, vasculitis, thrombotic microangiopathy or acute interstitial nephritis;

• Advanced cirrhosis (Child Pugh class C [score 10-15]), spontaneous bacterial peritonitis or hepatorenal syndrome;

• Acute peritoneal dialysis used as the initial RRT modality;

• Contraindications to albumin:

  1. Admitted with traumatic brain injury
  2. Increased intra-cranial pressure in those with intra-cranial pressure monitoring
  3. Prior history of anaphylaxis to intravenous albumin
  4. Contraindication or known objection to albumin/blood product transfusions

• Already received 2 or more RRT sessions during ICU admission.

• Limitations of medical therapy precluding RRT/mechanical ventilation/vasoactive medications or plan to transition to palliation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal Saline	0.9% Normal Saline (100 mL)	100 mL at the initiation of CRRT, SLED or IHD and another 100 mL 0.9% Normal Saline halfway through RRT sessions in ICU.
20-25% Albumin fluid	20-25% Albumin fluid (100 mL)	100 mL 20-25% Albumin fluid at the initiation of continuous renal replacement therapy (CRRT), prolonged intermittent renal replacement therapy (PIRRT), or intermittent hemodialysis (IHD) and another 100 mL 20-25% Albumin fluid and halfway through RRT sessions in ICU.

Primary Outcome Measures

Name	Time	Method
Organ-support-free days (OSFD)	28 days following randomization	Organ support-free days are defined as days that are both: 1) vasoactive therapy-free; AND 2) mechanical ventilation-free (including NIMV). For patients who die within 28 days following randomization, organ support-free days are counted as -1. An OSFD will be defined as the receipt of \< 2 hours of any vasoactive therapy provided by continuous infusion AND the receipt of \< 2 hours of either invasive or non-invasive mechanical ventilation, within a 24-hour period.

Secondary Outcome Measures

Name	Time	Method
Number of participants with death in ICU	Through 28 days	Mortality within 28 days since randomization
Number of participants with RRT dependence at 90 days among surviving patients	Through 90 days.	Defined by the receipt of any form of RRT within +/- 14 days of the 90-day time point following randomization for those alive at 90-days following randomization
Number of participants with death in ICU, at 28 days, and in-hospital	Through 90 days	Days from randomization to death in ICU, at 28 days or in-hospital
Major adverse kidney outcomes, defined as death, RRT dependence, or sustained reduction in kidney function (defined as eGFR < 75% baseline eGFR) at 90 days.	Through 90 days	eGFR will be derived from the CKD-EPI Creatinine (2021) equation that excludes the race-based coefficient69 and expressed in mL/min/1.73 m2
RRT-free days through day 28	Through day 28	For each patient, one point will be given for each calendar day that a patient was free of RRT. For patients who die within 28 days following randomization, RRT-free days are counted as -1.; An RRT-free day will be defined as a 24-period in which \< 2hours of CRRT was received within a 24-hour period and no intermittent RRT sessions were started during the 24-hour period.
Vasoactive therapy free days	Through day 28	For patients who die within 28 days following initiation of randomization, vasoactive therapy-free days are counted as -1.; Vasoactive therapy-free days will be defined as receipt of \< 2 hours of any vasoactive therapy provided by continuous infusion within a 24-hour period
Mechanical ventilation-free days	Though day 28.	For patients who die within 28 days following initiation of randomization, mechanical ventilation-free days are counted as -1.; Mechanical ventilation-free days will be defined as receipt of \< 2 hours of either invasive or non-invasive ventilation during a 24-hour period. Invasive mechanical ventilation is that provided via endotracheal tube (including tracheostomy). Noninvasive ventilation will be counted when more than 5 cm H2O of continuous positive airway pressure and more than 5 cm H2O of pressure support when deployed to avoid intubation. Other uses of noninvasive ventilation (eg, chronic nighttime use for chronic obstructive pulmonary disease) will not be counted.
eGFR will be evaluated in all patients alive at Day 90	At 90 days	Serum creatinine will be drawn at day 90 (or as close as possible to day 90) and not beyond 132 days after randomization (i.e. we will accept a serum creatinine from Day 90 minus 14 days to Day 90 plus 42 days). eGFR will be derived from the CKD-EPI Creatinine (2021) equation that excludes the race-based coefficient and expressed in mL/min/1.73 m2
Daily fluid balance after randomization up until ICU discharge or day 14, whichever comes first	Day 14 or ICU discharge	Daily net fluid will be calculated based on the medical chart
ICU free days	Through 28 days	For patients who die within 28 days following initiation of randomization, ICU-free days are counted as being -1.; ICU-free days will be defined as admission to an ICU for \< 2 hours within a 24-hour period
Number of participants with all-cause mortality at 28 days	Through 28 days	Mortality within 28 days since randomization
Number of participants with all-cause mortality at 90 days	Through 90 days.	Mortality within 90 days since randomization.
Hospitalization-free days	Through 90 days.	Defined as a 24-hour period completely free of an inpatient hospitalization.
EuroQoL EQ-5D-5L which includes a descriptive system (scored from 5 (worst) to 25 (best)) and a visual analogue scale (scored from 0 (worst) to 100 (best)) at day 90.	At 90 days	Survivors at 90 days will be contacted and evaluated using the EQ-5D-5L which is a measure of health-related quality of life and patient utility
Difference between ordered and achieved ultrafiltration for all intermittent HD / SLED treatments will be determined according to the medical record up until ICU discharge or day 14, whichever comes first	Day 14 or ICU discharge	volume will be determined according to the medical record
Daily Sequential Organ Failure Assessment score (SOFA) score after enrollment up until ICU discharge or day 14, whichever comes first	Day 14 or ICU discharge	The renal component of the SOFA score will be calculated on the basis of urine output only (as all participants will receive RRT and this impacts the creatinine value).; The GCS score will not be used for the total score (GCS score is difficult is accurately determine in an intubated and sedated participant)
Number of participants with all-cause mortality at 365 days	Through 365 days	Mortality within 365 days since randomization.
Number of participants with composite of death or RRT dependence at 90 days	Through 90 days.	Defined as death within 90-days following randomization or the receipt of any form of RRT within +/- 14 days of the 90-day time point following randomization
Occurrence of RRT-associated hypotension (for every RRT session in ICU after randomization)	Through 14 days	Defined as: a drop in blood pressure during RRT requiring initiation or increase in dose of a vasopressor during RRT session or premature discontinuation of RRT session due to hypotension
Health Care Costs	Through 365 days.	An economic evaluation will include the cost of the intervention and control will be assessed using a micro-costing approach,1plus any implications on length of stay, safety events associated with the intervention and/or control, and the costs associated with RRT-dependence up to 365 days following randomizationTo measure these impacts, we will assess hospital and ICU use, physician claims, and subsequent outpatient claims for RRT for all patients within the trial. Consistent with usual practice within a multi-centre clinical trial, valuation of costs will be done for the subset of all patients enrolled within the province of Ontario, Canada (extrapolated based on all patients in the trial) using administrative costing data available from the Institute for Clinical Evaluative Sciences (IC/ES).
Number of alive participants with RRT-dependence at 365 days	Through 365 days	defined by the patient having a kidney transplant or receipt of any form of RRT within 14 days before or after the 365-days post-randomization time-point

Trial Locations

Locations (16)

The Governors of the University of Calgary; 🇨🇦 Calgary, Alberta, Canada

University of Manitoba - Health Sciences Centre; 🇨🇦 Winnipeg, Manitoba, Canada

Nova Scotia Health Authority; 🇨🇦 Halifax, Nova Scotia, Canada

Hamilton Health Sciences Corporation; 🇨🇦 Hamilton, Ontario, Canada

Kingston General Hospital; 🇨🇦 Kingston, Ontario, Canada

Sunnybrook Health Sciences Centre; 🇨🇦 North York, Ontario, Canada

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada

University of Ottawa Heart Institute; 🇨🇦 Ottawa, Ontario, Canada

Scarborough Health Network; 🇨🇦 Scarborough, Ontario, Canada

Niagara Health System; 🇨🇦 St. Catharines, Ontario, Canada

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

Sinai Health System; 🇨🇦 Toronto, Ontario, Canada

Lakeridge Health; 🇨🇦 Whitby, Ontario, Canada

Centre Integre de Sante et de Services Sociaux de Laval; 🇨🇦 Laval, Quebec, Canada

Centre Integre Universitaire de Sante et de Services Sociaux de L'Estrie - Centre Hospitalier Universitaire de Sherbrooke; 🇨🇦 Sherbrooke, Quebec, Canada

University of Saskatchewan; 🇨🇦 Saskatoon, Saskatchewan, Canada