Amiloride in Nephrotic Syndrome (AMILOR)

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

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

Study Overview

• Status: Terminated
• Conditions: Edema; Nephrotic Syndrome; Sodium Retention
• Intervention / Treatment: Drug: Amiloride; Drug: Furosemide

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Anja Schork, MD; Phone Number: +49 7071 2982712; Email: Anja.Schork@med.uni-tuebingen.de
• Study Contact Backup: Name: Ferruh Artunc, Prof., MD; Phone Number: +49 7071 2982712; Email: Ferruh.Artunc@med.uni-tuebingen.de

Study Locations

• Germany
  • Baden-Wuerttemberg
    • Tuebingen, Baden-Wuerttemberg, Germany, 72076
      • University Hospital Tuebingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amiloride; Treatment wirh Amiloride, start dose 5 mg	Drug: Amiloride; Treatment with amiloride, start dose 5 mg
Active Comparator: Furosemide; Treatment with Furosemide, start dose 40 mg	Drug: Furosemide; Treatment with furosemide, start dose 40 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease of overhydration	Decrease of overhydration (OH) measured by bioimpedance spectroscopy	8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease of overhydration	Decrease of overhydration (OH) measured by bioimpedance spectroscopy	16 days
Decrease of body weight	Decrease of body weight	8 and 16 days
Decrease of edema cercumference	Decrease of edema cercumference, measured at the lower leg	8 and 16 days
Decrease of blood pressure	Decrease of systolic and diastolic blood pressure	8 and 16 days
Increase of urine volume and natriuresis	Increase of urine volume and natriuresis, measured in 24 hours collected urine	8 and 16 days
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
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
Occurrence of adverse events	Occurrence of adverse events	16 days

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Principal Investigator: Ferruh Artunc, Prof., MD, University Hospital Tuebingen

Publications and helpful links

General Publications

• 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.

Helpful Links

• Homepage working group Prof. Artunc

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2020
• Primary Completion (Actual): November 5, 2022
• Study Completion (Actual): November 20, 2022

Study Registration Dates

• First Submitted: October 2, 2021
• First Submitted That Met QC Criteria: October 2, 2021
• First Posted (Actual): October 15, 2021

Study Record Updates

• Last Update Posted (Actual): July 5, 2023
• Last Update Submitted That Met QC Criteria: July 1, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Nephrotic Syndrome; ENaC; Amiloride; Diuretic therapy; Proteasuria
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Disease; Water-Electrolyte Imbalance; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Syndrome; Nephrotic Syndrome; Nephrosis; Hypernatremia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Channel Blockers; Diuretics, Potassium Sparing; Sodium Potassium Chloride Symporter Inhibitors; Acid Sensing Ion Channel Blockers; Epithelial Sodium Channel Blockers; Furosemide; Amiloride
• Other Study ID Numbers: AmiloridNS-01; 2019-002607-18 (EudraCT Number)

Drug and device information, study documents

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