Amiloride in Nephrotic Syndrome

Study Overview
=================
Brief Summary
-----------------
The AMILOR study compares treatment of edema in nephrotic syndrome with Amiloride vs. 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.

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

Conditions
-----------------
Nephrotic Syndrome, Edema, Sodium Retention

Intervention / Treatment
-----------------
* Drug: Amiloride
* Drug: Furosemide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Acute nephrotic syndrome with proteinuria > 3 g/day and formation of edema. Age ≥ 18 years at the time of signing the informed consent. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures. Ability to adhere to the study visit schedule and other protocol requirements. 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. Subject (male or female) is willing to use highly effective methods of contraception according to the Clinical trial fertility group recommendations. Female Patients of childbearing potential (WOCBP) must agree to pregnancy testing before inclusion in the study. Female Patients must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation. All subjects must agree not to share medication. Exclusion Criteria: 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. Hypovolemia or dehydration. Uncontrolled diabetes mellitus. Hypotension, systolic blood pressure < 90 mmHg. Hyperkalemia, plasma potassium concentration > 4.8 mmol/l. Hypokalemia, plasma potassium concentration < 3.3 mmol/l. Hyponatremia, plasma sodium concentration < 128 mmol/l. Hypercalcemia, ionized calcium > 2.0 mmol/l or total albumin corrected calcium > 3.0 mmol/l. Signs of cardiac decompensation (orthopnoe, dyspnoe NYHA IV). Hepatic coma or precoma. Symptoms of gout. Current therapy with potassium-sparing diuretics (e.g. spironolactone) or potassium supplements. Women during pregnancy and lactation. 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. Any other clinical condition that would jeopardize the patient's safety while participating in this clinical trial. Active participation in other clinical trials or observation period of competing trials.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amiloride<br>Treatment wirh Amiloride, start dose 5 mg | Drug: Amiloride<br>* Treatment with amiloride, start dose 5 mg<br>|
| Active Comparator: Furosemide<br>Treatment with Furosemide, start dose 40 mg | Drug: Furosemide<br>* Treatment with furosemide, start dose 40 mg<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nephrotic Syndrome, ENaC, Diuretic therapy, Amiloride, Proteasuria