Condition category
Urological and Genital Diseases
Date applied
19/12/2020
Date assigned
29/12/2020
Last edited
14/01/2021
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Nephrotic syndrome is a kidney condition characterised by very high levels of protein in the urine (proteinuria), low levels of protein in the blood, and swelling, especially around the eyes, feet, and hands.
Furosemide is a type of medicine called a diuretic. It's used to treat high blood pressure, heart failure and edema (a build up of fluid in the body). It's also sometimes used to help you pee when your kidneys aren't working properly. Diuretics are sometimes called "water pills/tablets" because they make you pee more.
Our aim was to evaluate how nephrotic edema responds to a combined oral dose of furosemide, hydrochlorothizide and amiloride compared to intravenous furosemide.

Who can participate?
Adult patients with diagnosis of nephrotic syndrome and diuretic resistant edema.

What does the study involve?
Patients will be assigned to one of the two treatment groups.
Group 1 in which intravenous Furosemide is administered
Group 2 in which patients receive oral Furosemide and Hydrochlorothiazide/Amiloride
Clinical and laboratory measurements will be performed for 5 days.

What are the possible benefits and risks of participating?
All participants will have the opportunity to receive a detailed general evaluation and possible benefits regarding weight loss. There are the normal possible side effects of both treatments.

Where is the study run from?
Fundeni Clinical Institute (Romania)

When is the study starting and how long is it expected to run for?
January 2020 to December 2022

Who is funding the study?
Fundeni Clinical Institute (Romania)

Who is the main contact?
Dr Georgiana Fratila
georgianafratila27@gmail.com

Trial website

Contact information

Type

Scientific

Primary contact

Dr Georgiana Fratila

ORCID ID

Contact details

18 Aleea Sinaia
84A Building
Entrance 1
Apartment 60
10th Floor
Bucuresti
022765
Romania
+40 (0)747853133
valentina-georgiana.fratila@drd.umfcd.ro

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

46275

Study information

Scientific title

A prospective, randomized, unicentric study investigating the non-inferiority of combined oral diuretics furosemide and hydrochlorothiazide/amiloride to intravenous furosemide in patients with nephrotic edema and diuretic resistance

Acronym

FANS

Study hypothesis

Furosemide is traditionally the drug of choice when considering using a class of diuretics and new data show that ENaC blockade improves diuresis in patients with nephrotic edema, with effectively reduced swelling and body weight.

Ethics approval

Approved 08/09/2020, local ethical board of Fundeni Clinical Institute (Fundeni Street no. 258, 022328, Bucharest, Romania; +40 (0)724545131; secretariat@icfundeni.ro), ref: 46275

Study design

Prospective randomized unicentric study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a participant information sheet

Condition

Diuretic treatment in nephrotic syndrome and diuretic-resistant edema

Intervention

The study will include an estimated number of 20 patients, 10 patients in each treatment group. Patients will have a 24 h washout period with no diuretics administered and then, based on their FENa <0.2%, patients will be assigned to of the two treatment groups.
Computer-generated randomization will be performed using online software to generate block randomization.
Group 1 in which intravenous furosemide is administered, starting with a 40 mg bolus and then continuous administration of 5 mg/h, with dose adjustment according to urinary output (>5 l/24 h - dose decreased to 2.5 mg/h; <5 l/24 h - the same dose of 5 mg/h).
Group 2 in which patients receive furosemide 40 mg/day and hydrochlorothiazide/amiloride 50 and 5 mg/day, respectively.

Clinical and laboratory measurements will be performed as follows:
1. Clinical measurements: daily body weight, urinary output, systolic and diastolic blood pressure (2 times a day) and hydration status by bioimpedance
2. Laboratory measurements: serum markers (creatinine, urea, albumin, hematocrit, Na, K, Ca, Mg, bicarbonate, pH) at admission, at 24 hours and daily after randomization, urinary markers (creatinine, Na) for FENa and (Na, K) daily after randomization and 24 hours proteinuria, ACR 24 hours prior to randomization and at 5 days.

Intervention type

Drug

Phase

Not Applicable

Drug names

Furosemide, hydrocholorothizide, amiloride

Primary outcome measure

1. Weight measured at baseline and daily after randomization during the follow up period
2. Hydration status measured by bioimpedance at baseline and daily after randomization during the follow up period

Secondary outcome measures

1. Low blood pressure is established by daily measuring of blood pressure using a manual sphygmomanometer
2. Severe hyponatremia is established by daily measurement of serum sodium (blood test)
3. Hypokalemia and hyperkalemia is established by daily measurement of serum potassium (blood test)
4. Severe hypomagnesemia is established by daily measurement of serum magnesium (blood test)
5. Alcalosis is established by daily measurement of acid base balance (pH of venous blood gas sample)
6. Acute kidney injury is established by daily measurement of serum creatinine (blood test) and urinary output (over 24 h)
7. Aggravated hypervolemia at 3 days is established by fixed or increased body weight with clinical increased peripheral edema and urinary output <1.5 l/24 h

Overall trial start date

01/06/2020

Overall trial end date

01/05/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Age >18 years old
2. Nephrotic syndrome in patients without diabetes mellitus
3. Diuretic resistance
4. eGFR >30 ml/min/1.73 m²

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

20

Participant exclusion criteria

1. Age <18 years old
2. Nephrotic syndrome in patients with type 1 or type 2 diabetes
3. eGFR <30 ml/min/1.73 m²
4. Hypokalemia and hyperkalemia
5. Severe hyponatremia
6. Alcalosis
7. Severe pulmonary congestion
8. Active infection
9. NSAIDs use within the last month
10. Pregnancy
11. Kidney transplant
12. Known allergy to furosemide, hydrochlorothiazide or amiloride
13. Patients with a defibrillator/pacemaker/metal prosthesis

Recruitment start date

01/02/2021

Recruitment end date

31/12/2022

Locations

Countries of recruitment

Romania

Trial participating centre

Fundeni Clinical institute
Department of Nephrology Fundeni Fundeni Street no. 258 District no. 2
Bucharest
022328
Romania

Sponsor information

Organisation

Institutul Clinic Fundeni

Sponsor details

Fundeni Street no. 258 District no. 2
Bucuresti
022328
Romania
-
gener732000@yahoo.com

Sponsor type

Hospital/treatment centre

Website

https://icfundeni.ro/

Funders

Funder type

Hospital/treatment centre

Funder name

Fundeni Clinical Institute

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Intention to publish date

31/12/2023

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

14/01/2021: Internal review. 29/12/2020: Trial’s existence confirmed by Fundeni Clinical Institute