Furosemide Stress Test Guiding Initiation of Renal Replacement Therapy

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

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

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Device: Dialysis with continuous renal replacement therapy; Device: Mechanical ventilator; Drug: Anti-Bacterial Agents; Drug: Vasopressors

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

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Thailand
  • Pathumwan
    • Bangkok, Pathumwan, Thailand, 10330
      • Sasipha tachaboon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early renal replacement therapy; 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; Continuous renal replacement therapy is a form of 24-hour dialysis in the ICU; Device: Mechanical ventilator; Invasive or noninvasive form of respiratory support; Drug: Anti-Bacterial Agents; Antibacterial agents deemed appropriate by physicians in the ICU; Other Names: cephalosporin; carbapenem; Drug: Vasopressors; Vasopressors such as Norepinephrine, dopamine, milrinone, dobutamine; Other Names: Dobutamine; Milrinone; Norepinephrine; Dopamine
Placebo Comparator: Conventional renal replacement therapy; 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; Continuous renal replacement therapy is a form of 24-hour dialysis in the ICU; Device: Mechanical ventilator; Invasive or noninvasive form of respiratory support; Drug: Anti-Bacterial Agents; Antibacterial agents deemed appropriate by physicians in the ICU; Other Names: cephalosporin; carbapenem; Drug: Vasopressors; Vasopressors such as Norepinephrine, dopamine, milrinone, dobutamine; Other Names: Dobutamine; Milrinone; Norepinephrine; Dopamine

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

Collaborators and Investigators

• Sponsor: Chulalongkorn University
• Investigators: Principal Investigator: Nattachai Srisawat, MD, Excellence Center of Critical Care Nephrology, Chulalongkorn University

Publications and helpful links

General Publications

• Lumlertgul N, Peerapornratana S, Trakarnvanich T, Pongsittisak W, Surasit K, Chuasuwan A, Tankee P, Tiranathanagul K, Praditpornsilpa K, Tungsanga K, Eiam-Ong S, Kellum JA, Srisawat N; FST Study Group. Early versus standard initiation of renal replacement therapy in furosemide stress test non-responsive acute kidney injury patients (the FST trial). Crit Care. 2018 Apr 19;22(1):101. doi: 10.1186/s13054-018-2021-1.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: March 18, 2016
• First Submitted That Met QC Criteria: March 31, 2016
• First Posted (Estimate): April 6, 2016

Study Record Updates

• Last Update Posted (Actual): December 19, 2017
• Last Update Submitted That Met QC Criteria: December 17, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: critical care; Acute kidney injury; Furosemide stress test
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Dopamine Agents; Phosphodiesterase Inhibitors; Adrenergic beta-Agonists; Sympathomimetics; Adrenergic beta-1 Receptor Agonists; Phosphodiesterase 3 Inhibitors; Anti-Bacterial Agents; Norepinephrine; Milrinone; Dopamine; Dobutamine; Vasoconstrictor Agents; Cephalosporins
• Other Study ID Numbers: IRB.006/59

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No