Furosemide Alone or Unexpectedly With Solution of Hypertonic Saline in Nephrotic Syndrome (FLUSH-NS)

HSS (Hypertonic Saline Solution) Plus High Dose Furosemide vs High Dose Furosemide in Nephrotic Syndrome - a Randomized Trial

The trial will test the hypothesis that hypertonic saline on top of standard diuretic treatment will help achieve adequate diuresis in patients with nephrotic syndrome.

Study Overview

• Status: Recruiting
• Conditions: Nephrotic Syndrome
• Intervention / Treatment: Drug: Hypertonic saline; Drug: Furosemide Injection

Detailed Description

Objectives:

Edema is one of the major clinical manifestations of nephrotic syndrome. All patients are initially treated with diuretics and sodium restriction but the results are sometimes not satisfactory. Hypertonic saline solutions have been studied in congestive heart failure and a meta-analysis confirmed it's role in achieving adequate diuresis and protecting patients against acute kidney injury although the proposed mechanism of action is not known (osmotic action?, inhibition of renin-angiotensin-aldostrerone system?, increase in renal perfusion?, myocardial contractility?). The investigators therefore hypothesized that it may exert beneficial effects also in nephrotic syndrome.

Treatment protocol:

A prospective placebo-controlled randomized trial. Subjects will be randomized to high-dose furosemide vs high-dose furosemide plus hypertonic intravenous saline in a 1:1 fashion. All subjects will receive furosemide tid (starting with 3x40 mg i.v.) with or without hypertonic saline solution (3x100 ml of 3% NaCl - in a combined infusion lasting 10 minutes). Subjects randomized to furosemide only will receive 3x100 ml of 5% glucose (in a combined infusion lasting 10 minutes). The dose of furosemide will be determined by the investigator based on patients weight, severity of edema, 24-h urine volume, kidney function. In case of poor clinical response (urine volume below 1000 ml) the investigator will be able to titrate the furosemide dose up to 3x180 mg i.v. All patients will be kept on low-salt diet and water restriction (500-1000 ml/day), their weight will assessed every morning before breakfast and measurement of 24-h urine volume will be performed every day. Additionally BNP levels will be measured at baseline and after 5 days of treatment. Treatment will be continued for 5 days. The primary measure of efficacy will be urine volume and the rate of acute kidney injury (AKI), secondary measure of efficacy will be the expected decrease in brain natriuretic peptides (BNP) levels and the length of hospitalization.

Hydrochlorothiazide, spironolactone and other diuretics use will be contraindicated during the study. Patients will be required to receive standard concurrent therapy as determined by their attending physician and according to current guidelines (including steroids and other immunosuppresives).

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alicja Rydzewska-Rosolowska, MD; Phone Number: +48858317885; Email: alicja.rosolowska@umb.edu.pl

Study Locations

• Poland
  • Bialystok, Poland, 15-276
    • Recruiting
    • II Department of Nephrology and Hypertension
    • Contact: Alicja Rydzewska-Rosolowska, MD; Phone Number: +48858317885; Email: alicja.rosolowska@umb.edu.pl

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:

• 30 consecutive patients with nephrotic syndrome (proteinuria over 3.5 g/day, edema, hypoalbuminemia, dysproteinemia) admitted to II Nephrology Department from November 2018 onwards within 48h of admission,
• age above 18,
• informed consent.

Exclusion Criteria:

• AKI (acute kidney injury) - AKIN criteria level 3,
• CKD (chronic kidney disease) stage 4 and 5 according to KDIGO (Kidney Disease: Improving Global Outcomes),
• concomittant heart failure NYHA (New York Heart Association) class III or worse,
• active liver disease and liver failure,
• terminal neoplastic disease,
• serum sodium above 145 mmol/l,
• pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: high-dose furosemide & hypertonic saline; furosemide i.v., 3% NaCl	Drug: Hypertonic saline; high dose furosemide with hypertonic saline 3x daily; Other Names: 3% saline; Drug: Furosemide Injection; high dose furosemide
Active Comparator: high-dose furosemide; furosemide i.v.	Drug: Furosemide Injection; high dose furosemide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diuresis	ml of diuresis	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospitalisation	days	14 days
BNP levels	pg/ml	5 days

Collaborators and Investigators

• Sponsor: Medical University of Bialystok
• Investigators: Principal Investigator: Alicja Rydzewska-Rosolowska, MD, Medical University of Białystok

Publications and helpful links

General Publications

• Paterna S, Parrinello G, Amato P, Dominguez L, Pinto A, Maniscalchi T, Cardinale A, Licata A, Amato V, Licata G, Di Pasquale P. Tolerability and efficacy of high-dose furosemide and small-volume hypertonic saline solution in refractory congestive heart failure. Adv Ther. 1999 Sep-Oct;16(5):219-28.
• Licata G, Di Pasquale P, Parrinello G, Cardinale A, Scandurra A, Follone G, Argano C, Tuttolomondo A, Paterna S. Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects. Am Heart J. 2003 Mar;145(3):459-66. doi: 10.1067/mhj.2003.166.
• Paterna S, Di Pasquale P, Parrinello G, Amato P, Cardinale A, Follone G, Giubilato A, Licata G. Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure. Eur J Heart Fail. 2000 Sep;2(3):305-13. doi: 10.1016/s1388-9842(00)00094-5.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2018
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: November 20, 2018
• First Submitted That Met QC Criteria: November 20, 2018
• First Posted (Actual): November 21, 2018

Study Record Updates

• Last Update Posted (Actual): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 19, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: diuretics
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Syndrome; Nephrotic Syndrome; Nephrosis; 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: IIKNT-001/2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

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