Back to resultsAmiloride in Nephrotic Syndrome (AMILOR)
Primary Purpose
Nephrotic Syndrome, Edema, Sodium Retention
Status
Terminated
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Amiloride
Furosemide
Sponsored by
About this trial
This is an interventional treatment trial for Nephrotic Syndrome focused on measuring Nephrotic Syndrome, ENaC, Diuretic therapy, Amiloride, Proteasuria
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.
Sites / Locations
- University Hospital Tuebingen
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Amiloride
Furosemide
Arm Description
Treatment wirh Amiloride, start dose 5 mg
Treatment with Furosemide, start dose 40 mg
Outcomes
Primary Outcome Measures
Decrease of overhydration
Decrease of overhydration (OH) measured by bioimpedance spectroscopy
Secondary Outcome Measures
Decrease of overhydration
Decrease of overhydration (OH) measured by bioimpedance spectroscopy
Decrease of body weight
Decrease of body weight
Decrease of edema cercumference
Decrease of edema cercumference, measured at the lower leg
Decrease of blood pressure
Decrease of systolic and diastolic blood pressure
Increase of urine volume and natriuresis
Increase of urine volume and natriuresis, measured in 24 hours collected urine
Course of plasma renin activity and serum aldosterone concentration
Course of plasma renin activity and serum aldosterone concentration, measured in blood samples
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
Occurrence of adverse events
Occurrence of adverse events
Full Information
NCT ID
NCT05079789
First Posted
October 2, 2021
Last Updated
July 1, 2023
Sponsor
University Hospital Tuebingen
1. Study Identification
Unique Protocol Identification Number
NCT05079789
Brief Title
Amiloride in Nephrotic Syndrome
Acronym
AMILOR
Official Title
Randomized, Controlled Interventional Trial to Investigate the Efficacy of Amiloride for the Treatment of Edema in Human Nephrotic Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
Low recruiting rate and decision to evaluate as pilot study
Study Start Date
June 8, 2020 (Actual)
Primary Completion Date
November 5, 2022 (Actual)
Study Completion Date
November 20, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Tuebingen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nephrotic Syndrome, Edema, Sodium Retention
Keywords
Nephrotic Syndrome, ENaC, Diuretic therapy, Amiloride, Proteasuria
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Amiloride
Arm Type
Experimental
Arm Description
Treatment wirh Amiloride, start dose 5 mg
Arm Title
Furosemide
Arm Type
Active Comparator
Arm Description
Treatment with Furosemide, start dose 40 mg
Intervention Type
Drug
Intervention Name(s)
Amiloride
Intervention Description
Treatment with amiloride, start dose 5 mg
Intervention Type
Drug
Intervention Name(s)
Furosemide
Intervention Description
Treatment with furosemide, start dose 40 mg
Primary Outcome Measure Information:
Title
Decrease of overhydration
Description
Decrease of overhydration (OH) measured by bioimpedance spectroscopy
Time Frame
8 days
Secondary Outcome Measure Information:
Title
Decrease of overhydration
Description
Decrease of overhydration (OH) measured by bioimpedance spectroscopy
Time Frame
16 days
Title
Decrease of body weight
Description
Decrease of body weight
Time Frame
8 and 16 days
Title
Decrease of edema cercumference
Description
Decrease of edema cercumference, measured at the lower leg
Time Frame
8 and 16 days
Title
Decrease of blood pressure
Description
Decrease of systolic and diastolic blood pressure
Time Frame
8 and 16 days
Title
Increase of urine volume and natriuresis
Description
Increase of urine volume and natriuresis, measured in 24 hours collected urine
Time Frame
8 and 16 days
Title
Course of plasma renin activity and serum aldosterone concentration
Description
Course of plasma renin activity and serum aldosterone concentration, measured in blood samples
Time Frame
8 and 16 days
Title
Changes of dose of study medication and need for co-medication
Description
Number of required changes of dose of study medication and need for co-medication with HCT
Time Frame
8 and 16 days
Title
Occurrence of adverse events
Description
Occurrence of adverse events
Time Frame
16 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ferruh Artunc, Prof., MD
Organizational Affiliation
University Hospital Tuebingen
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Tuebingen
City
Tuebingen
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
72076
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
30597733
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.
Results Reference
background
Links:
URL
https://www.medizin.uni-tuebingen.de/de/das-klinikum/einrichtungen/kliniken/medizinische-klinik/innere-medizin-iv/forschung/nierenphysiologie
Description
Homepage working group Prof. Artunc
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Amiloride in Nephrotic Syndrome
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