Amiloride in Nephrotic Syndrome

Edema Clinical Trial

— AMILOR  

Official title:

Randomized, Controlled Interventional Trial to Investigate the Efficacy of Amiloride for the Treatment of Edema in Human Nephrotic Syndrome

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05079789
• Other study ID #: AmiloridNS-01
• Secondary ID: 2019-002607-18
• Status: Terminated
• Phase: Phase 3
• Start date: June 8, 2020
• Est. completion date: November 20, 2022

Study information

• Verified date: July 2023
• Source: University Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The AMILOR study compares treatment of edema in nephrotic syndrome with Amiloride vs. Furosemide.

Description:

The monocenter randomized-controlled AMILOR trial investigates the efficacy of the ENaC blocker amiloride in reducing edema in nephrotic syndrome compared with standard therapy with the loop diuretic furosemide. Patients with acute nephrotic syndrome are randomized to receive amiloride (starting dose 5 mg) or furosemide (starting dose 40 mg) for 16 days. The target number of patients is n = 18 per arm. Exclusion criteria include GFR <30ml/min/1.73m², AKIN 1 and 2, hypotension, hyper-/ hypokalemia, and hyponatremia. Overhydration is quantified by bioimpedance spectroscopy. Depending on the course of overhydration, dose adjustments (day 2, 5, 8, 12) or addition of HCT (day 8) are performed during the course of the study. Primary endpoint is decrease in overhydration at day 8, secondary endpoints include decrease in overhydration at day 16, as well as body weight, edema volume, blood pressure, urine volume, natriuresis at day 8 and 16, and need for dose adjustments and co-medication with HCT. Plasma potassium, sodium, and creatinine concentrations are measured as safety parameters.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: November 20, 2022
• Est. primary completion date: November 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Acute nephrotic syndrome with proteinuria > 3 g/day and formation of edema.

2. Age = 18 years at the time of signing the informed consent.

3. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.

4. Ability to adhere to the study visit schedule and other protocol requirements.

5. Use of adequate thrombosis prophylaxis due to the increased risk of thrombosis in nephrotic syndrome and the expected fluctuations in volume balance during study participation.

6. Subject (male or female) is willing to use highly effective methods of contraception according to the "Clinical trial fertility group" recommendations.

7. Female Patients of childbearing potential (WOCBP) must agree to pregnancy testing before inclusion in the study.

8. Female Patients must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation.

9. All subjects must agree not to share medication.

Exclusion Criteria:

1. Severe reduction of kidney function: Creatinine clearance or calculated GFR < 30 mL/min/1.73m² or acute kidney injury KDIGO stage 2 or 3 or anuria.

2. Hypovolemia or dehydration.

3. Uncontrolled diabetes mellitus.

4. Hypotension, systolic blood pressure < 90 mmHg.

5. Hyperkalemia, plasma potassium concentration > 4.8 mmol/l.

6. Hypokalemia, plasma potassium concentration < 3.3 mmol/l.

7. Hyponatremia, plasma sodium concentration < 128 mmol/l.

8. Hypercalcemia, ionized calcium > 2.0 mmol/l or total albumin corrected calcium > 3.0 mmol/l.

9. Signs of cardiac decompensation (orthopnoe, dyspnoe NYHA IV).

10. Hepatic coma or precoma.

11. Symptoms of gout.

12. Current therapy with potassium-sparing diuretics (e.g. spironolactone) or potassium supplements.

13. Women during pregnancy and lactation.

14. History of hypersensitivity to the investigational medicinal product, comparator or co-medication or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product, comparator or co-medication.

15. Any other clinical condition that would jeopardize the patient's safety while participating in this clinical trial.

16. Active participation in other clinical trials or observation period of competing trials.

Related Conditions & MeSH terms

• Edema
• Hypernatremia
• Nephrosis
• Nephrotic Syndrome
• Sodium Retention
• Syndrome

Intervention

Drug:
• Amiloride
Treatment with amiloride, start dose 5 mg
• Furosemide
Treatment with furosemide, start dose 40 mg

Locations

Country	Name	City	State
Germany	University Hospital Tuebingen	Tuebingen	Baden-Wuerttemberg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Artunc F, Worn M, Schork A, Bohnert BN. Proteasuria-The impact of active urinary proteases on sodium retention in nephrotic syndrome. Acta Physiol (Oxf). 2019 Apr;225(4):e13249. doi: 10.1111/apha.13249. Epub 2019 Jan 18. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Decrease of overhydration	Decrease of overhydration (OH) measured by bioimpedance spectroscopy	8 days
Secondary	Decrease of overhydration	Decrease of overhydration (OH) measured by bioimpedance spectroscopy	16 days
Secondary	Decrease of body weight	Decrease of body weight	8 and 16 days
Secondary	Decrease of edema cercumference	Decrease of edema cercumference, measured at the lower leg	8 and 16 days
Secondary	Decrease of blood pressure	Decrease of systolic and diastolic blood pressure	8 and 16 days
Secondary	Increase of urine volume and natriuresis	Increase of urine volume and natriuresis, measured in 24 hours collected urine	8 and 16 days
Secondary	Course of plasma renin activity and serum aldosterone concentration	Course of plasma renin activity and serum aldosterone concentration, measured in blood samples	8 and 16 days
Secondary	Changes of dose of study medication and need for co-medication	Number of required changes of dose of study medication and need for co-medication with HCT	8 and 16 days
Secondary	Occurrence of adverse events	Occurrence of adverse events	16 days

External Links

•   Homepage working group Prof. Artunc