Standard Versus Accelerated Initiation of Dialysis in Acute Kidney Injury

Acute Kidney Injury Clinical Trial

— STARRT-AKI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01557361
• Other study ID #: CIHR MOP 111116
• Status: Completed
• Phase: Phase 2
• First received: March 13, 2012
• Last updated: September 11, 2014
• Start date: May 2012
• Est. completion date: October 2013

Study information

• Verified date: August 2013
• Source: St. Michael's Hospital, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: October 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Kidney Injury

Intervention

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.
• 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

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	St. Joseph's Healthcare	Hamilton	Ontario
Canada	London Health Sciences Centre - University Hospital	London	Ontario
Canada	London Health Sciences Centre - Victoria Hospital	London	Ontario
Canada	The Ottawa Hospital, Civic Campus	Ottawa	Ontario
Canada	The Ottawa Hospital, General Campus	Ottawa	Ontario
Canada	Centre hopitalier universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
St. Michael's Hospital, Toronto	Alere San Diego, Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Feasibility of enrollment	>50% of eligible patients are successfully enrolled in the trial	14 days	No
Secondary	Feasibility of 90-day follow-up	Vital status and need for RRT at 90 days are successfully captured in >95% of participants	90 days	No
Secondary	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	Yes