Clinical trial NCT05079789: Amiloride in Nephrotic Syndrome
Official title: Randomized, Controlled Interventional Trial to Investigate the Efficacy of Amiloride for the Treatment of Edema in Human Nephrotic Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Nephrotic Syndrome
Edema
Sodium Retention
Keywords: Nephrotic Syndrome
ENaC
Diuretic therapy
Amiloride
Proteasuria
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2021-10-15
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Decrease of Overhydration, %ECW After 8 Days
timeFrame: 8 days
Secondary outcomes:
measure: Decrease of Overhydration, %ECW After 16 Days
timeFrame: 16 days
measure: Decrease of Body Weight, kg
timeFrame: 8 days
Other outcomes:
Locations:
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen
state: Baden-Wuerttemberg
Study officials:
affiliation: University Hospital Tuebingen
name: Ferruh Artunc, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.