Furosemide Alone or Unexpectedly With Solution of Hypertonic Saline in Nephrotic Syndrome

NCT ID: NCT03750136

Last Updated: 2022-11-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-15
• Study Completion Date: 2023-03-01

Brief Summary

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.

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).

Conditions

Nephrotic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

high-dose furosemide & hypertonic saline

furosemide i.v., 3% NaCl

Group Type: EXPERIMENTAL

Hypertonic saline

Intervention Type: DRUG

high dose furosemide with hypertonic saline 3x daily

Furosemide Injection

Intervention Type: DRUG

high dose furosemide

high-dose furosemide

furosemide i.v.

Group Type: ACTIVE_COMPARATOR

Furosemide Injection

Intervention Type: DRUG

high dose furosemide

Interventions

Hypertonic saline

high dose furosemide with hypertonic saline 3x daily

Intervention Type: DRUG

Furosemide Injection

high dose furosemide

Intervention Type: DRUG

Other Intervention Names

3% saline

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Bialystok

OTHER

Sponsor Role: lead

Responsible Party

Alicja Rydzewska-Rosołowska

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alicja Rydzewska-Rosolowska, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Białystok

Locations

II Department of Nephrology and Hypertension

Bialystok, , Poland

Site Status: RECRUITING

Countries

Poland

Central Contacts

Alicja Rydzewska-Rosolowska, MD

Role: CONTACT

alicja.rosolowska@umb.edu.pl

+48858317885

Facility Contacts

Alicja Rydzewska-Rosolowska, MD

Role: primary

alicja.rosolowska@umb.edu.pl

+48858317885

References

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.

Reference Type: BACKGROUND

PMID: 12660669 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10915397 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10938493 (View on PubMed)

Other Identifiers

IIKNT-001/2018

Identifier Type: -

Identifier Source: org_study_id