Furosemide Stress Test Guiding Initiation of Renal Replacement Therapy

Study Overview
=================
Brief Summary
-----------------
Does Early Initiation of Renal Replacement Therapy Have an Impact on 7-day Fluid Balance in Critically Ill Patients with Acute Kidney Injury with Positive Furosemide Stress Test?: a Multicenter Randomized Controlled Trial

Detailed Description
-----------------
The objective is to determine if early initiation of renal replacement therapy guided by positive furosemide stress test has an impact on 7-day fluid balance in critically ill patients with acute kidney injury

Official Title
-----------------
Does Early Initiation of Renal Replacement Therapy Have an Impact on 7-day Fluid Balance in Critically Ill Patients With Acute Kidney Injury With Positive Furosemide Stress Test?: a Multicenter Randomized Controlled Trial

Conditions
-----------------
Acute Kidney Injury

Intervention / Treatment
-----------------
* Device: Dialysis with continuous renal replacement therapy
* Device: Mechanical ventilator
* Drug: Anti-Bacterial Agents
* Drug: Vasopressors


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age older than 18 years old and admission in an ICU Acute kidney injury (defined by serum creatinine increase ≥ 0.3 mg/dL or urine output ≤ 0.5 mL/kg/hour according to KDIGO criteria) Informed consent provided by the patient or person with decisional responsibility Indwelling bladder catheter Documented cause of acute kidney injury from acute tubular necrosis e.g. presence of granular or epithelial casts on urine sediment, FeNa more than 1%, Feurea more than 50%, urine or plasma neutrophil gelatinase-associated lipocalin (NGAL) more than 150 mg/dL Opinion of the treating clinical team that patient was well resuscitated and sufficiently clinically stable for the intervention or by noninvasive or invasive measurements i.e. fluid accumulation at least 5% plus at least one of the following e.g. chest radiography, central venous pressure ≥ 8 mmHg, pulse pressure variation < 13%, inferior vena cava collapsibility index < 50% in spontaneously breathing patients or distensibility index < 18% in mechanically ventilated patients Exclusion Criteria: Baseline serum creatinine ≥ 2 mg/dL (male) and ≥ 1.5 mg/dL (female) within 3 months Evidence of volume depletion at the time of furosemide administration or active bleeding Evidence of obstructive uropathy, renal vein thrombosis or renal artery stenosis, thrombotic microangiopathy, glomerulonephritis, tumor lysis syndrome History of renal allograft Known pregnancy Allergy or known sensitivity to loop diuretics Need for emergency renal replacement therapy at randomization or evaluation by the clinical team that the renal replacement therapy should be deferred Patient is moribund with expected death within 24 hr or whom survival to 28 days is unlikely due to an uncontrollable comorbidity (cardiac, pulmonary or hepatic end-stage disease; hepatorenal syndrome; poorly controlled cancer; severe post-anoxic encephalopathy; etc.) Patients with advance directives issued expressing the desire not to be resuscitated Prior treatment with RRT within 30 days

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early renal replacement therapy<br>Dialysis with continuous renal replacement therapy machine e.g. Aquarius, Prismaflex, Infomed, starting within 12 hours after randomization Patients will receive standard treatments such as anti-bacterial agents, mechanical ventilator, vasopressors as appropriate | Device: Dialysis with continuous renal replacement therapy<br>* Continuous renal replacement therapy is a form of 24-hour dialysis in the ICU<br>Device: Mechanical ventilator<br>* Invasive or noninvasive form of respiratory support<br>Drug: Anti-Bacterial Agents<br>* Antibacterial agents deemed appropriate by physicians in the ICU<br>* Other names: carbapenem;Drug: Vasopressors<br>* Vasopressors such as Norepinephrine, dopamine, milrinone, dobutamine<br>* Other names: Dobutamine;|
| Placebo Comparator: Conventional renal replacement therapy<br>Dialysis with continuous renal replacement therapy machine e.g. Aquarius, Prismaflex, Infomed, after the patients reached at least one of the following criteria; pH < 7.15 or serum HCO3 < 15 mEq/L serum K >= 6 mEq/L Signs of volume overload or P/F ratio < 200 BUN > 60 mg/dL Patients will receive standard treatments such as anti-bacterial agents, mechanical ventilator, vasopressors as appropriate | Device: Dialysis with continuous renal replacement therapy<br>* Continuous renal replacement therapy is a form of 24-hour dialysis in the ICU<br>Device: Mechanical ventilator<br>* Invasive or noninvasive form of respiratory support<br>Drug: Anti-Bacterial Agents<br>* Antibacterial agents deemed appropriate by physicians in the ICU<br>* Other names: carbapenem;Drug: Vasopressors<br>* Vasopressors such as Norepinephrine, dopamine, milrinone, dobutamine<br>* Other names: Dobutamine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal replacement therapy proportion | Proportion of patients with FST responsiveness and nonresponsiveness who had received RRT | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day mortality measured by number of deceased patients at 28-day after the enrollment | 28-day mortality measured by number of deceased patients at 28-day after the enrollment | 28-day or until hospital discharge | 
| ICU-free days measured by number of days (28 days minus ICU length of stay) | 28 days minus by ICU length of stay | through study completion, an average of 28 days | 
| mechanical ventilator-free days measured by number of days (28 days minus days using mechanical ventilator) | 28 days minus by days using mechanical ventilator | through study completion, an average of 28 days | 
| dialysis dependence measured by need for renal replacement therapy in 28 days | dialysis dependence at hospital discharge | through study completion, an average of 28 days | 
| 7-day fluid balance | 7-day fluid balance | 7 days | 
| RRT free days | 28 days minus by days on RRT | through study completion, an average of 28 days | 
| Length of ICU stay | Length of ICU stay | through study completion, an average of 28 days | 
| Length of hospital stay | Length of hospital stay | through study completion, an average of 28 days | 
| Renal recovery | Urine output > 1,000 ml without diuretics or > 2,000 ml with diuretics | through study completion, an average of 28 days | 
| Adverse events | Adverse events | through study completion, an average of 28 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute kidney injury, Furosemide stress test, critical care