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

STandard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI)

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

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Other: Accelerated RRT initiation; Other: Standard RRT initiation

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare
    • London, Ontario, Canada, N6A 4G5
      • London Health Sciences Centre - Victoria Hospital
    • London, Ontario, Canada, N6C 6B5
      • London Health Sciences Centre - University Hospital
    • Ottawa, Ontario, Canada, K1Y 4E9
      • The Ottawa Hospital, Civic Campus
    • Ottawa, Ontario, Canada, K1H8L6
      • The Ottawa Hospital, General Campus
    • Toronto, Ontario, Canada, M5G1X5
      • Mount Sinai Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hopitalier Universitaire de Sherbrooke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Standard RRT initiation; 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.	Other: Standard RRT initiation; Patients will be carefully followed over a period of 7 days to identify potential indications for RRT. The trial team will ask that the clinical team consider RRT initiation if there are: I. Criteria for persistent AKI (serum creatinine has not declined by more than 50% from value recorded at time of eligibility) AND II. At least one of the following indications for RRT initiation: Serum potassium ≥6.0 mmol/L, or; Serum bicarbonate ≤ 10 mmol/L, or; Evidence of severe respiratory failure, based on a PaO2/FiO2 <200 and bilateral infiltrates on the chest x-ray, or; By 72 hours after randomization, creatinine has not declined by more than 50% from that recorded at the time of randomization
EXPERIMENTAL: Accelerated RRT initiation; A dialysis catheter will be placed and RRT initiated as soon as possible and within 12 hours of eligibility.	Other: Accelerated RRT initiation; A dialysis catheter will be placed and RRT initiated as soon as possible and within 12 hours of eligibility. This 12 hour window includes the time needed to obtain consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of protocol adherence	>90% of participants in the accelerated initiation arm start RRT within 12 hours of eligibility AND >90% of participants randomized to the standard initiation arm who ultimately receive RRT, start RRT at least 12 hours following eligibility determination	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of enrollment	>50% of eligible patients are successfully enrolled in the trial	14 days
Feasibility of 90-day follow-up	Vital status and need for RRT at 90 days are successfully captured in >95% of participants	90 days
Safety outcomes	Serious adverse effects, with a particular focus on those that are potentially attributable to the study treatment, vascular accesss complications (including hemorrhage, thrombosis and infection) and complications associated with the delivery of RRT (dialysis-associated hypotension, electrolyte abnormalities) will be examined.	14 days

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: Canadian Institutes of Health Research (CIHR); Alere San Diego

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (ACTUAL): August 1, 2013
• Study Completion (ACTUAL): October 1, 2013

Study Registration Dates

• First Submitted: March 13, 2012
• First Submitted That Met QC Criteria: March 15, 2012
• First Posted (ESTIMATE): March 19, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): September 12, 2014
• Last Update Submitted That Met QC Criteria: September 11, 2014
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: dialysis; acute kidney injury; hemodialysis; critical illness; renal replacement therapy
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: CIHR MOP 111116