Clinical trial NCT01557361: Standard Versus Accelerated Initiation of Dialysis in Acute Kidney Injury
Official title: STandard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Kidney Injury
Keywords: renal replacement therapy
dialysis
acute kidney injury
hemodialysis
critical illness
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Alere San Diego
First posted: 2012-03-19
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of this trial are to determine whether, in critically ill patients with severe acute kidney injury (AKI), randomization to accelerated initiation of renal replacement therapy (RRT), compared with standard initiation, is:

1. Feasible, in terms of adherence to the protocol (primary outcome), recruitment rates, and achievement of follow-up; and
2. Safe, from the perspective of potential adverse events associated with earlier initiation of RRT

Detailed description: Acute kidney injury (AKI) is a common and devastating complication of critical illness. Once AKI is established, treatment is largely supportive and no intervention has been found to restore kidney function or improve overall survival. Renal replacement therapy (RRT), usually in the form of hemodialysis, is frequently needed to manage patients with severe AKI. Such patients have an in-hospital mortality that consistently exceeds 50%. Delay in the initiation of RRT has been implicated as a possible contributor to this poor outcome. A recent meta-analysis suggested that earlier initiation of RRT may improve survival. However, completed trials to date have been small, single centre, limited by study quality, and have shown considerable heterogeneity in terms of definitions used for "early" RRT initiation.

The objectives of this trial are to determine whether, in critically ill patients with severe acute kidney injury (AKI), randomization to accelerated initiation of renal replacement therapy (RRT), compared with standard initiation, is:

1. Feasible, in terms of adherence to the protocol (primary outcome), recruitment rates, and achievement of follow-up; and
2. Safe, from the perspective of potential adverse events associated with the earlier or later initiation of RRT

This pilot trial is intended to guide and inform the design of a phase III multicentre randomized trial of accelerated versus standard initiation of RRT in critically ill patients that will evaluate the impact of the intervention on 90-day all-cause mortality and recovery of kidney function.

Eligibility criteria: Inclusion Criteria (all of these need to be present):

1. Age ≥ 18 years
2. Admission to an intensive care unit
3. Evidence of kidney dysfunction (serum creatinine ≥ 100 µmol/L (women) or

   ≥ 130 µmol/L (men))
4. Evidence of severe AKI defined by at least 2 of the following 3 criteria:

   i-A 2-fold increase in serum creatinine during hospitalization or from a known pre-hospitalization baseline ii-Oliguria as defined by total urine output \< 6 mL/kg over the preceding 12 hours iii-Whole blood Neutrophil Gelatinase-Associated Lipocalin (NGAL) ≥ 400ng/mL
5. Likelihood that an absolute indication for RRT will not arise in the subsequent 24 hours based on the most recent bloodwork for the following parameters: i- Serum potassium ≤ 5.5 mmol/L and ii- Serum bicarbonate ≥ 15 mmol/L
6. Central venous pressure ≥ 8 mmHg

Exclusion Criteria (the presence of one of these would disqualify eligibility):

1. Lack of commitment to ongoing life support
2. Presence of a drug overdose that necessitates initiation of RRT
3. Any RRT within the previous 2 months
4. Presence or clinical suspicion of renal obstruction, rapidly progressive glomerulonephritis, vasculitis, or acute interstitial nephritis
5. Advanced chronic kidney disease, defined by an estimated glomerular filtration rate \< 30 mL/min/1.73 m2, based on pre-hospitalization blood work
6. Kidney transplant within the past 365 days
7. At the time of screening, doubling of serum creatinine has been present for \> 48 hours
8. Clinician(s) caring for patient believe(s) that immediate dialysis is absolutely mandated
9. Clinician(s) caring for patient believe(s) that deferral of dialysis initiation is mandated
10. Patient or substitute decision maker can not provide consent within 12 hours of study eligibility

Primary outcomes:
measure: Feasibility of protocol adherence
timeFrame: 14 days
Secondary outcomes:
measure: Feasibility of enrollment
timeFrame: 14 days
measure: Feasibility of 90-day follow-up
timeFrame: 90 days
measure: Safety outcomes
timeFrame: 14 days
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre - University Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital, General Campus
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital, Civic Campus
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Sherbrooke
country: Canada
facility: Centre hopitalier universitaire de Sherbrooke
state: Quebec
Study officials:
affiliation: Unity Health Toronto
name: Ron Wald, MDCM MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Sean M Bagshaw, MD MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Smith OM, Wald R, Adhikari NK, Pope K, Weir MA, Bagshaw SM; Canadian Critical Care Trials Group. Standard versus accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI): study protocol for a randomized controlled trial. Trials. 2013 Oct 5;14:320. doi: 10.1186/1745-6215-14-320.