Standard Versus Accelerated Initiation of Dialysis in Acute Kidney Injury (STARRT-AKI)

Unity Health Toronto

Status and phase: Completed; Phase 2

Conditions: Acute Kidney Injury

Treatments: Other: Standard RRT initiation; Other: Accelerated RRT initiation

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01557361

CIHR MOP 111116

Details and patient eligibility

About

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

Full 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.

Enrollment: 100 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Standard RRT initiation

Active Comparator group

Description:

RRT is initiated \>12 hours after eligibility determination. Once a decision is made to start RRT, a dialysis catheter will be placed and RRT initiated as soon as possible.

Treatment:

Other: Standard RRT initiation

Accelerated RRT initiation

Experimental group

Description:

A dialysis catheter will be placed and RRT initiated as soon as possible and within 12 hours of eligibility.

Treatment:

Other: Accelerated RRT initiation