Edema, Nephrotic Syndrome, Sodium Retention
Conditions
Keywords
Nephrotic Syndrome, ENaC, Diuretic therapy, Amiloride, Proteasuria
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.
Interventions
DRUGAmiloride
Treatment with amiloride, start dose 5 mg
DRUGFurosemide
Treatment with furosemide, start dose 40 mg
Sponsors
University Hospital Tuebingen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Decrease of Overhydration, %ECW After 8 Days | 8 days | Decrease of overhydration (OH) measured by bioimpedance spectroscopy, expressed as percent of extracellular water (%ECW) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Decrease of Overhydration, %ECW After 16 Days | 16 days | Decrease of overhydration (OH) measured by bioimpedance spectroscopy, expressed as percent of extracellular water (%ECW) |
| Decrease of Body Weight, kg | 8 days | Decrease of body weight after 8 days |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Amiloride Treatment wirh Amiloride, start dose 5 mg
Amiloride: Treatment with amiloride, start dose 5 mg | 10 |
| Furosemide Treatment with Furosemide, start dose 40 mg
Furosemide: Treatment with furosemide, start dose 40 mg | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Total | Furosemide | Amiloride |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 8 Participants | 8 Participants |
| Age, Continuous | 51 years | 50 years | 51 years |
| Race/Ethnicity, Customized Ethnicity European | 19 Participants | 10 Participants | 9 Participants |
| Race/Ethnicity, Customized Ethnicity Indian | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Germany | 20 participants | 10 participants | 10 participants |
| Sex: Female, Male Female | 7 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 13 Participants | 8 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 9 / 10 | 10 / 10 |
| serious Total, serious adverse events | 1 / 10 | 4 / 10 |
Outcome results
Primary
Decrease of Overhydration, %ECW After 8 Days
Decrease of overhydration (OH) measured by bioimpedance spectroscopy, expressed as percent of extracellular water (%ECW)
Time frame: 8 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amiloride | Decrease of Overhydration, %ECW After 8 Days | 1.95 %ECW |
| Furosemide | Decrease of Overhydration, %ECW After 8 Days | 5.15 %ECW |
Secondary
Decrease of Body Weight, kg
Decrease of body weight after 8 days
Time frame: 8 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amiloride | Decrease of Body Weight, kg | 3.8 kg |
| Furosemide | Decrease of Body Weight, kg | 2.0 kg |
Secondary
Decrease of Overhydration, %ECW After 16 Days
Decrease of overhydration (OH) measured by bioimpedance spectroscopy, expressed as percent of extracellular water (%ECW)
Time frame: 16 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amiloride | Decrease of Overhydration, %ECW After 16 Days | 10.10 %ECW |
| Furosemide | Decrease of Overhydration, %ECW After 16 Days | 7.40 %ECW |