Oral furosemide and hydrochlorothiazide/amiloride versus intravenous furosemide for the treatment of nephrotic edema
| ISRCTN | ISRCTN28785798 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN28785798 |
| Secondary identifying numbers | 46275 |
- Submission date
- 19/12/2020
- Registration date
- 29/12/2020
- Last edited
- 07/12/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Urological and Genital Diseases
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
Contact information
Scientific
18 Aleea Sinaia
84A Building
Entrance 1
Apartment 60
10th Floor
Bucuresti
022765
Romania
| Phone | +40 (0)747853133 |
|---|---|
| valentina-georgiana.fratila@drd.umfcd.ro |
Study information
| Study design | Prospective randomized unicentric study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| 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 |
| Study 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(s) | 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 |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/06/2020 |
| Overall study end date | 01/05/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 20 |
| Total final enrolment | 22 |
| 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 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
Study participating centre
Fundeni Street no. 258 District no. 2
Bucharest
022328
Romania
Sponsor information
Hospital/treatment centre
Fundeni Street no. 258 District no. 2
Bucuresti
022328
Romania
| gener732000@yahoo.com | |
| Website | https://icfundeni.ro/ |
"ROR" |
https://ror.org/05w6fx554 |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | 31/12/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in nephrology journals such as American Journal of Kidney Diseases, BCM Nephrology, Kidney International etc. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Gener Ismail (gener732000@yahoo.com). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 01/11/2023 | 07/12/2023 | Yes | No |
Editorial Notes
07/12/2023: Publication reference and total final enrolment added.
03/02/2021: Publication and dissemination plan added.
14/01/2021: Internal review.
29/12/2020: Trial’s existence confirmed by Fundeni Clinical Institute
