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

Sponsor

Unity Health Toronto (Other)

Overall Status

Completed

CT.gov ID

NCT01557361

Collaborator

Canadian Institutes of Health Research (CIHR) (Other), Alere San Diego (Industry)

100

Enrollment

Locations

Arms

Duration (Months)

9.1

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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:

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

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury	Other: Accelerated RRT initiation Other: Standard RRT initiation	Phase 2

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.

Feasible, in terms of adherence to the protocol (primary outcome), recruitment rates, and achievement of follow-up; and
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 Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2012

Actual Primary Completion Date :

Aug 1, 2013

Actual Study Completion Date :

Oct 1, 2013

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Feasibility of protocol adherence [14 days]
>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

Secondary Outcome Measures

Feasibility of enrollment [14 days]
>50% of eligible patients are successfully enrolled in the trial
Feasibility of 90-day follow-up [90 days]
Vital status and need for RRT at 90 days are successfully captured in >95% of participants
Safety outcomes [14 days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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

≥ 130 µmol/L (men))

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

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
Central venous pressure ≥ 8 mmHg

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
2	St. Joseph's Healthcare	Hamilton	Ontario	Canada	L8N 4A6
3	London Health Sciences Centre - Victoria Hospital	London	Ontario	Canada	N6A 4G5
4	London Health Sciences Centre - University Hospital	London	Ontario	Canada	N6C 6B5
5	The Ottawa Hospital, General Campus	Ottawa	Ontario	Canada	K1H8L6
6	The Ottawa Hospital, Civic Campus	Ottawa	Ontario	Canada	K1Y 4E9
7	St. Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8
8	University Health Network	Toronto	Ontario	Canada	M5G 2N2
9	Mount Sinai Hospital	Toronto	Ontario	Canada	M5G1X5
10	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada
11	Centre hopitalier universitaire de Sherbrooke	Sherbrooke	Quebec	Canada	J1H 5N4