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

Phase 4

Terminated

• Conditions: Acute Kidney Injury
• Interventions: Drug: Furosemide

• Registration Number: NCT03731117
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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.

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 Timeline

• Study First Submitted: 2018-10-10
• Study First Submitted QC: 2018-11-02
• Study First Posted: 2018-11-06
• Study Start: 2019-07-15
• Status Verified: 2020-12
• Primary Completion: 2020-12-07
• Study Completion: 2020-12-07
• Last Update Submitted: 2020-12-11
• Last Update Posted: 2020-12-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 11

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
FST	Furosemide	FUROSEMIDE STRESS TEST

Primary Outcome Measures

Name	Time	Method
Need for renal replacement therapy or death	Before day 7	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.
sensitivity	3 hour after FST	FST will be positive if patient is non responder : 2-hour urine output \< 200mL

Secondary Outcome Measures

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

Trial Locations

Locations (3)

Hopital Bichat; 🇫🇷 Paris, France

CH Cote Basque; 🇫🇷 Bayonne, France

Hopital Saint Louis; 🇫🇷 Paris, France