Clinical trial NCT04705896: Albumin To Enhance Recovery After Acute Kidney Injury
Official title: Albumin To Enhance Recovery After Acute Kidney Injury: A Multi-Centre, Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Acute Kidney Injury
Renal Replacement Therapy
Hypotension
Critical Illness
Keywords: Albumin
Normal Saline
Dialysis
Intensive Care Unit
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: The Physicians' Services Incorporated Foundation
name: The Kidney Foundation of Canada
name: The Ottawa Hospital Academic Medical Organization (TOHAMO) Innovation Fund Grant.
name: Canadian Institutes of Health Research (CIHR)
name: Canadian Blood Services
name: Héma-Québec
First posted: 2021-01-12
Enrollment: 856
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized controlled trial with two parallel arms 1:1
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Organ-support-free days (OSFD)
timeFrame: 28 days following randomization
Secondary outcomes:
measure: RRT-free days through day 28
timeFrame: Through day 28
measure: Vasoactive therapy free days
timeFrame: Through day 28
measure: Mechanical ventilation-free days
timeFrame: Though day 28.
measure: ICU free days
timeFrame: Through 28 days
measure: Number of participants with death in ICU
timeFrame: Through 28 days
measure: Number of participants with all-cause mortality at 28 days
timeFrame: Through 28 days
measure: Number of participants with all-cause mortality at 90 days
timeFrame: Through 90 days.
measure: Number of participants with death in ICU, at 28 days, and in-hospital
timeFrame: Through 90 days
measure: Number of participants with RRT dependence at 90 days among surviving patients
timeFrame: Through 90 days.
measure: Number of participants with composite of death or RRT dependence at 90 days
timeFrame: Through 90 days.
measure: eGFR will be evaluated in all patients alive at Day 90
timeFrame: At 90 days
measure: Major adverse kidney outcomes, defined as death, RRT dependence, or sustained reduction in kidney function (defined as eGFR < 75% baseline eGFR) at 90 days.
timeFrame: Through 90 days
measure: Hospitalization-free days
timeFrame: Through 90 days.
measure: 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.
timeFrame: At 90 days
measure: Occurrence of RRT-associated hypotension (for every RRT session in ICU after randomization)
timeFrame: Through 14 days
measure: Daily fluid balance after randomization up until ICU discharge or day 14, whichever comes first
timeFrame: Day 14 or ICU discharge
measure: 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
timeFrame: Day 14 or ICU discharge
measure: Daily Sequential Organ Failure Assessment score (SOFA) score after enrollment up until ICU discharge or day 14, whichever comes first
timeFrame: Day 14 or ICU discharge
measure: Health Care Costs
timeFrame: Through 365 days.
measure: Number of alive participants with RRT-dependence at 365 days
timeFrame: Through 365 days
measure: Number of participants with all-cause mortality at 365 days
timeFrame: Through 365 days
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: The Governors of the University of Calgary
state: Alberta
city: Winnipeg
country: Canada
facility: University of Manitoba - Health Sciences Centre
state: Manitoba
city: Halifax
country: Canada
facility: Nova Scotia Health Authority
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corporation
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: North York
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Scarborough
country: Canada
facility: Scarborough Health Network
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health System
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sinai Health System
state: Ontario
city: Whitby
country: Canada
facility: Lakeridge Health
state: Ontario
city: Laval
country: Canada
facility: Centre Integre de Sante et de Services Sociaux de Laval
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Integre Universitaire de Sante et de Services Sociaux de L'Estrie - Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Saskatoon
country: Canada
facility: University of Saskatchewan
state: Saskatchewan
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Edward G Clark, MD MSc FRCPC
role: PRINCIPAL_INVESTIGATOR
References: