FURosemide Stress Test to Predict Need of Renal Replacement THERapy in Ischemic Acute Tubular Necrosis in ICU (FURTHER)

Ischemic acute tubular necrosis (ATN) is one of the main cause of acute kidney injury (AKI) in intensive care units (ICU). Sepsis and cardio-pulmonary bypass (CPB) are major providers. There is no validated tool to predict the evolution of AKI is ICU. Furosemide Stress Test (FST) may predict evolution of ATN-related AKI outside ICU in terms of progressive AKI, need for renal replacement therapy (RRT) or inpatient mortality with improved performance comparing to biomarkers. FST has not been validated in a prospective cohort in ICU in the settings of ischemic ATN. FURTHER aim to determine whether FST would be a useful tool to identify patients with slight to moderate AKI (KDIGO stage 1 and 2) who will evolve towards need for RRT following AKIKI (The Artificial Kidney Initiation in Kidney Injury ) delayed initiation criteria.

Study Overview

• Status: Terminated
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Drug: Furosemide

Detailed Description

FURTHER will enroll consecutive patients with AKI KDIGO stage 1 or 2 associated with a sepsis or following a cardiac surgery with CPB within 72h. Patients must have achieved a hemodynamic stabilization confirmed by clinical (no need for intravenous fluids, no significant variation of noradrenaline) and non-clinical (trans-thoracic echocardiography, passive leg rise or other validated tool) assessment. Included patients will receive 1 to 1.5 mg/kg of FUROSEMIDE. Urine output will be measured for 6 hours and compensated by the same volume of intravenous crystalloids. Need for RRT will be assess at 2-hour, 6-hour and daily up to day 7, following the AKIKI-study delayed initiation arm criteria. FURTHER aim to evaluate FST in a well-defined prospective cohort of ischemic ATN-related AKI as predictor of need for RRT within a week.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Bayonne, France
    • CH Cote Basque
  • Paris, France, 75010
    • Hopital Saint Louis
  • Paris, France, 75018
    • Hôpital Bichat

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 over 18 years old
• Hospitalized in ICU at day of inclusion
• Diagnosis of sepsis defined as proven or suspected infection and increase of the SOFA (Sequential Organ Failure Assessment) score by 2 points or more compared to basal OR Cardiothoracic surgery with CBP (Cardiopulmonary bypass) within 72 hours before inclusion
• Adequate cardiac output and volemia assessed by cardiac ultrasound, venous saturation in Oxygen (ScVO2) or ΔPP
• Hemodynamic stabilization : stable norepinephrine dosage (or <20% variations) with no vascular filling during the last 3 hours
• AKI stage I or II in KDIGO classification

Exclusion Criteria:

• Chronic Kidney Disease with glomerular filtration rate ≤ 30 ml/mn/1,73m2
• Obstructive AKI
• AKI stage III in KDIGO classification
• Known allergy to loop diuretics
• Contraindications to Furosemide
• FST not feasible within 12 hours of eligibility
• Previous AKI during the same hospitalization
• Pregnancy or breastfeeding women
• Subject under a legal protective measure
• No affiliation to a social regime or CMU

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FST; FUROSEMIDE STRESS TEST	Drug: Furosemide; Furosemide (FUROSEMIDE®) 20 mg / 2ml, ampoule for injection 1 mg / kg slow intravenous injection 1.5 mg / kg if chronic exposure to diuretics in the week prior to inclusion Measurement of urine output after two and six hours. Compensation of diuresis by same volume of crystalloids over a 6-hour period; Other Names: furosemide stress test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for renal replacement therapy or death	Need for renal replacement therapy will be define according to the AKIKI study (Gaudry S, Hajage D, Schortgen F, Martin-Lefevre L, Pons B, Boulet E, et al. Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit. N Engl J Med. 2016 Jul 14;375(2):122-33). Need for RRT following AKIKI delayed initiation criteria. FST performance will be compared to the need of RRT or death.	Before day 7
sensitivity	FST will be positive if patient is non responder : 2-hour urine output < 200mL	3 hour after FST

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 hour urine output	measurement of urine out	6 hour after FST
percentage of effective renal replacement therapy	Initiation of RRT	daily up to day 7
death		daily up to day 7
hemodynamic safety: noradrenaline dose	noradrenaline dose	6 hour after FST
clinical safety: arterial pressure	modification of systolic, diastolic or mean arterial blood pressure	6 hour after FST

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2019
• Primary Completion (Actual): December 7, 2020
• Study Completion (Actual): December 7, 2020

Study Registration Dates

• First Submitted: October 10, 2018
• First Submitted That Met QC Criteria: November 2, 2018
• First Posted (Actual): November 6, 2018

Study Record Updates

• Last Update Posted (Actual): December 16, 2020
• Last Update Submitted That Met QC Criteria: December 11, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: ICU; sepsis; Renal Replacement Therapy; Intensive care units; AKI; Ischemic Acute Kidney Injury; FST; FUROSEMIDE STRESS TEST; RRT; Cardio-pulmonary bypass
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Necrosis; Acute Kidney Injury; Kidney Tubular Necrosis, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: P170404J

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No