Standard vs. Accelerated Initiation of RRT in Acute Kidney Injury (STARRT-AKI: Principal Trial)

Study Overview
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Brief Summary
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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 to standard initiation, leads to: Improved survival (primary outcome); and Recovery of kidney function (principal secondary outcome), defined as independence from RRT at 90 days

Detailed Description
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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% with delays in RRT initiation implicated as a possible contributor. A recent meta-analysis suggested that earlier initiation of RRT may improve survival, but this is based on data derived overwhelmingly from observational studies. The investigators recently completed a multi-centre randomized controlled pilot trial that confirmed the feasibility of allocating patients to two different strategies of RRT initiation. Patient recruitment and follow-up, as well as patient safety, were successfully demonstrated during the pilot phase of this research program. The optimal timing of RRT initiation is an existing knowledge gap and a clear priority for investigation.

Official Title
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STandard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI): A Multi-Centre, Randomized, Controlled Trial (Principal Trial)

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Other: Standard RRT initiation
* Other: Accelerated RRT initiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Admission to an intensive care unit (ICU) Evidence of kidney dysfunction [serum creatinine ≥100 µmol/L (women) and ≥ 130 µmol/L (men)] Evidence of severe AKI defined by at least 1 of the following 3 criteria: i) ≥ 2-fold increase in serum creatinine from a known pre-morbid baseline or during the current hospitalization; OR ii) Achievement of a serum creatinine ≥ 354 µmol/L with evidence of a minimum increase of 27 µmol/L from pre-morbid baseline or during the current hospitalization; OR iii) Urine output < 6.0 mL/kg over the preceding 12 hours Exclusion Criteria: Serum potassium > 5.5 mmol/L Serum bicarbonate < 15 mmol/L Presence of a drug overdose that necessitates initiation of RRT Lack of commitment to ongoing life support (including RRT) Any RRT within the previous 2 months (either acute or chronic RRT) Kidney transplant within the past 365 days Known pre-hospitalization advanced chronic kidney disease, defined by an estimated glomerular filtration rate < 20 mL/min/1.73 m2 Presence or clinical suspicion of renal obstruction, rapidly progressive glomerulonephritis, vasculitis, thrombotic microangiopathy or acute interstitial nephritis Clinician(s) caring for patient believe(s) that immediate RRT is mandated Clinician(s) caring for patient believe(s) that deferral of RRT initiation is mandated at their discretion, clinicians may administer a bolus of intravenous furosemide (ie, furosemide stress test) and evaluate the subsequent urine output to help guide decision making regarding the likelihood of AKI progression

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard RRT initiation<br>RRT initiation will be guided by the presence of one or more clinical indications. Even in the absence of one of these indications, RRT may be commenced at the discretion of the treating physician. | Other: Standard RRT initiation<br>* In the absence of kidney function recovery, the initiation of RRT will be permitted if one of the following develops: serum potassium ≥ 6.0 mmol/L; pH ≤ 7.20 or serum bicarbonate ≤ 12 mmol/L; evidence of severe respiratory failure, based on a PaO2/FiO2 ≤ 200 and clinical perception of volume overload; and/or persistent AKI > 72 hours following the time of randomization.<br>|
| Experimental: Accelerated RRT initiation<br>A dialysis catheter will be placed and RRT initiated as soon as possible and within 12 hours of the patient meeting the eligibility criteria. | Other: Accelerated RRT initiation<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality. |  | 90 days following study randomization. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RRT dependence |  | 90 days following study randomization. | 
| Composite of death or RRT dependence. |  | 90 days following study randomization. | 
| Measurement of estimated glomerular filtration rate. |  | 90 days following study randomization. | 
| Measurement of albuminuria. |  | 90 days following study randomization. | 
| Major adverse kidney outcomes. | Defined as death, RRT dependence or sustained reduction in kidney function (defined as eGFR < 75% baseline eGFR). | 90 days following study randomization. | 
| Mechanical ventilation-free days. |  | Measured from randomization through day 28. | 
| Vasoactive therapy-free days |  | Measured from randomization through day 28. | 
| ICU-free days |  | Measured from randomization through day 28. | 
| Hospitalization-free days |  | Measured from randomization through day 90. | 
| Death in ICU |  | Measured in-hospital and at day 28. | 
| EuroQoL EQ-5D-5L. | A measure of health-related quality of life and patient utility. | Measured at day 90 and at day 365. | 
| Health care costs. |  | Measured from baseline through day 365. | 
| Composite of death or RRT dependence. |  | Measured at day 365. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal replacement therapy, Acute kidney injury, Dialysis, Hemodialysis, Critical illness