Standard Versus Accelerated Initiation of Dialysis in Acute Kidney Injury

NCT ID: NCT01557361

Last Updated: 2014-09-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2013-10-31

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.

Conditions

Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Standard RRT initiation

Intervention Type: OTHER

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:

1. Serum potassium ≥6.0 mmol/L, or

2. Serum bicarbonate ≤ 10 mmol/L, or

3. Evidence of severe respiratory failure, based on a PaO2/FiO2 <200 and bilateral infiltrates on the chest x-ray, or

4. By 72 hours after randomization, creatinine has not declined by more than 50% from that recorded at the time of randomization

Accelerated RRT initiation

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

Group Type: EXPERIMENTAL

Accelerated RRT initiation

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: 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:

1. Serum potassium ≥6.0 mmol/L, or

2. Serum bicarbonate ≤ 10 mmol/L, or

3. Evidence of severe respiratory failure, based on a PaO2/FiO2 <200 and bilateral infiltrates on the chest x-ray, or

4. By 72 hours after randomization, creatinine has not declined by more than 50% from that recorded at the time of randomization

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Alere San Diego

INDUSTRY

Sponsor Role: collaborator

Unity Health Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ron Wald, MDCM MPH

Role: PRINCIPAL_INVESTIGATOR

Unity Health Toronto

Sean M Bagshaw, MD MSc

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

University of Alberta Hospital

Edmonton, Alberta, Canada

St. Joseph's Healthcare

Hamilton, Ontario, Canada

London Health Sciences Centre - Victoria Hospital

London, Ontario, Canada

London Health Sciences Centre - University Hospital

London, Ontario, Canada

The Ottawa Hospital, General Campus

Ottawa, Ontario, Canada

The Ottawa Hospital, Civic Campus

Ottawa, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

University Health Network

Toronto, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Centre hopitalier universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Countries

Canada

References

Wing S, Neto AS, Bellomo R, Clark EG, Gallagher M, Liangos O, Prasad B, Silver SA, Tolwani A, Bagshaw S, Wald R. CKD Progression after Acute Kidney Injury: A Secondary Analysis of the Standard versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury Trial. Kidney360. 2025 Apr 1;6(4):636-644. doi: 10.34067/KID.0000000663. Epub 2024 Dec 3.

Reference Type: DERIVED

PMID: 39625781 (View on PubMed)

Fayad AI, Buamscha DG, Ciapponi A. Timing of kidney replacement therapy initiation for acute kidney injury. Cochrane Database Syst Rev. 2022 Nov 23;11(11):CD010612. doi: 10.1002/14651858.CD010612.pub3.

Reference Type: DERIVED

PMID: 36416787 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24093950 (View on PubMed)

Other Identifiers

CIHR MOP 111116

Identifier Type: -

Identifier Source: org_study_id