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

• ClinicalTrials.gov Identifier: NCT03731117
• Recruitment Status: Terminated
• First Posted: November 6, 2018
• Last Update Posted: December 16, 2020
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Kidney Injury	Drug: Furosemide	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Prospective, non-comparative, multicenter, study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: FURosemide Stress Test to Predict Need of Renal Replacement THERapy in Ischemic Acute Tubular Necrosis in ICU
• Actual Study Start Date: July 15, 2019
• Actual Primary Completion Date: December 7, 2020
• Actual Study Completion Date: December 7, 2020

Arms and Interventions

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 Name: furosemide stress test

Outcome Measures

Primary Outcome Measures :

1. Need for renal replacement therapy or death [ Time Frame: 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.

2. sensitivity [ Time Frame: 3 hour after FST ]
   FST will be positive if patient is non responder : 2-hour urine output < 200mL

Secondary Outcome Measures :

1. 6 hour urine output [ Time Frame: 6 hour after FST ]
   measurement of urine out
2. percentage of effective renal replacement therapy [ Time Frame: daily up to day 7 ]
   Initiation of RRT
3. death [ Time Frame: daily up to day 7 ]
4. hemodynamic safety: noradrenaline dose [ Time Frame: 6 hour after FST ]
   noradrenaline dose
5. clinical safety: arterial pressure [ Time Frame: 6 hour after FST ]
   modification of systolic, diastolic or mean arterial blood pressure

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

France

CH Cote Basque

Bayonne, France

Hopital Saint Louis

Paris, France, 75010

Hopital Bichat

Paris, France, 75018

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT03731117
• Other Study ID Numbers: P170404J
• First Posted: November 6, 2018
• Last Update Posted: December 16, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Ischemic Acute Kidney Injury; Intensive care units; AKI; ICU; FST; FUROSEMIDE STRESS TEST; RRT; Renal Replacement Therapy; sepsis; Cardio-pulmonary bypass

Additional relevant MeSH terms:

Acute Kidney Injury; Kidney Tubular Necrosis, Acute; Necrosis; Pathologic Processes; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Furosemide; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Sodium Potassium Chloride Symporter Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action