Liberation From Acute Dialysis

Study Overview
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Brief Summary
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The goal of the LIBERATE-D clinical trial is to improve outcomes for patients recovering from dialysis-requiring acute kidney injury (AKI-D). The impact of a conservative dialysis strategy compared to standard clinical practice of thrice-weekly dialysis will be examined to help generate knowledge for how to guide delivery of dialysis to facilitate renal recovery.

Detailed Description
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Dialysis-requiring acute kidney injury (AKI-D) is a devastating complication among hospitalized patients for which there are no treatments other than supportive care. Recovery of sufficient renal function to stop dialysis is an unequivocally important clinical and patient-oriented outcome. Shortening dialysis duration and increasing the number of AKI-D patients who recover would have a major clinical, public health and cost-saving impact. However, there is currently no evidence to guide the delivery of dialysis to facilitate recovery. The investigators hypothesize that in patients who have AKI-D and who are hemodynamically stable, a conservative dialysis strategy--in which hemodialysis is not continued unless specific metabolic or clinical indications for renal replacement therapy (RRT) are present--will improve the likelihood of renal recovery compared with the current standard clinical practice of thrice-weekly intermittent dialysis. The investigators have conducted a pilot clinical trial to demonstrate the feasibility of this approach. The investigators propose here a 2-center randomized controlled trial to test a conservative dialysis strategy in a larger AKI-D population (N = 220).

Official Title
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LIBERation From AcuTE Dialysis

Conditions
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Acute Kidney Injury, Kidney; Disease, Acute, Dialysis Related Complication

Intervention / Treatment
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* Procedure: Dialysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age Inpatient with AKI-D (intermittent hemodialysis or continuous renal replacement therapy received on at least one calendar day) at least partially due t acute tubular necrosis per the clinical nephrology team Hemodynamic stability: not requiring vasopressor support and with planned intermittent dialysis Baseline estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2 Exclusion Criteria: Nontraditional indication for dialysis (end-stage liver disease awaiting transplantation, fulminant hepatic failure, intoxication) Complete nephrectomy as cause of AKI-D Kidney transplant during index hospitalization Dialysis > 3 months Decompensated heart failure requiring left ventricular assist device or continuous inotropic support Mechanical ventilation via endotracheal tube Hypoxemia requiring significant oxygen support: >5 liters/min via nasal cannula or equivalent via face mask/tracheostomy mask to maintain oxygen saturation > 95%, or requiring fraction of inspired oxygen >50% in patients with tracheostomy requiring invasive or non-invasive ventilation Unable to consent and no surrogate decisionmaker available Pregnant Prisoner Clinical team declines to allow study participation Anticipated discharge or transfer from study hospital within 48 hours

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: Conventional<br>Thrice-weekly intermittent dialysis until pre-specified criteria for recovery are met | Procedure: Dialysis<br>* Dialysis treatment, either in the form of hemodialysis or continuous renal replacement therapy (if patient develops hemodynamic instability)<br>|
| Experimental: Conservative<br>Conservative dialysis strategy--dialysis prescribed only when specific metabolic or clinical indications are met. These indications are: blood urea nitrogen >112 mg/dL (40 mmol/L; blood potassium concentration >6 mmol/L; blood potassium concentration >5.5 mmol/L despite medical treatment; arterial blood gas pH <7.15, or in the absence of an available blood gas, serum bicarbonate <12 mmol/L, acute pulmonary edema due to fluid overload, responsible for hypoxemia requiring oxygen flow rate >5 L/min or equivalent via face mask/tracheostomy mask to maintain SpO2 >95% or requiring FiO2 >50% in patients with tracheostomy already on invasive or non-invasive mechanical ventilation and despite diuretic therapy; clinician judgement | Procedure: Dialysis<br>* Dialysis treatment, either in the form of hemodialysis or continuous renal replacement therapy (if patient develops hemodynamic instability)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with renal recovery at hospital discharge | Alive and off dialysis at the time of discharge, with sustained independence from dialysis for 14 days. This outcome does not require that all 14 days of sustained independence occur in-hospital. | Up to 14 days after hospital discharge (to allow for ascertainment of outcome at hospital discharge, which requires a period of sustained dialysis independence) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of dialysis sessions/week | Number of dialysis sessions prescribed in each treatment arm, expressed per week. | Up to 28 days | 
| Dialysis-free days to study day 28 | The number of days that a patient did not need dialysis to study day 28. A patient can only accrue dialysis-free days after the final dialysis session that commences the monitoring period for renal recovery. Subjects who die before study day 28 will be considered to have zero dialysis-free days. | Up to 28 days |