A New Application of Amiloride in the Treatment of Patient With Chronic Kidney Disease In Reducing Urinary PROtein (ANTI-UPRO)
Primary Purpose
Chronic Kidney Diseases
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Amiloride
Hydrochlorothiazide
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Kidney Diseases
Eligibility Criteria
Inclusion Criteria:
- Patients at the age of more than 14 years old with chronic kidney disease
- Good compliance of treatment
- PCR≥500mg/g.cr ,more than double confirmed
- Patients who written informed consent
Exclusion Criteria:
- less than 14 years of age
- eGFR≤30ml/min.1.73m2;
- poor compliance of treatment
- Previously intolerant or allergic to hydrochlorothiazide
- Patients with history of gout within six months
- Patients with active infection
- Patients with severe cardiopulmonary disease and dysfunction of central nervous system
- history of malignancy
- life expectancy is less than 1 years
- women who are pregnant,lactating and lack of contraception.
- enrolled in other clinical trials within 3 months
- patients who have used immunosuppressive agents or corticosteroids recently or in the past 12 weeks.
- patients without informed consent written or who enable or unwilling to comply with protocol approved by researchers.
Sites / Locations
- Nephrology Dept,Guangdong General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
amiloride
hydrochlorothiazide
Arm Description
Amiloride first for 8 weeks, then for a washout for 4 weeks, and cross over to receive hydrochlorothiazide for another 8 weeks
hydrochlorothiazide first for 8 weeks, then for a washout for 4 weeks, and cross over to receive amiloride for another 8 weeks.
Outcomes
Primary Outcome Measures
The remission of proteinuria
Secondary Outcome Measures
estimated Glomerular Filtration Rate
time to a 50% reduction in baseline estimated Glomerular filtration rate (according to CKD-EPI) and to doubling of baseline creatinine
creatinine
time to doubling of baseline creatinine
hyperkalemia
The ratio of hyperkalemia occurred at 12 weeks after treatment.
Full Information
NCT ID
NCT03170336
First Posted
May 26, 2017
Last Updated
September 16, 2020
Sponsor
Guangdong Provincial People's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03170336
Brief Title
A New Application of Amiloride in the Treatment of Patient With Chronic Kidney Disease In Reducing Urinary PROtein
Acronym
ANTI-UPRO
Official Title
The Effect and Safety of Amiloride in Decreasing Proteinuria for Patients With Chronic Kidney Disease in a Prospective , Crossover, Open-label Study.
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
March 1, 2018 (Actual)
Primary Completion Date
August 1, 2020 (Actual)
Study Completion Date
August 1, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Guangdong Provincial People's Hospital
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
Nowadays, the prevalence of chronic kidney disease (CKD) in China is about 10.8%,and nearly 120 million people suffer from CKD, which has become a serious public health problem in China. Study confirmed that proteinuria is an independent risk factor for the continuous deterioration of glomerular filtration rate (GFR) in patients with CKD. So it is of great significance to explore the strategy of reducing proteinuria.
According to our previous study, Amiloride can inhibit the expression of uPAR in podocytes and reduce proteinuria, This clinical trial aims to evaluate the effect and safety of Amiloride in decreasing proteinuria for patients with Chronic Kidney Disease.
Detailed Description
Amiloride is a Na+ channel blocker and has been used as a diuretic. It mainly inhibits the exchange of Na+-K+ and Na+-H+ in the distal tubule and collecting duct of the kidney, thus increasing the excretion of Na+ and water, reducing the excretion of K+ and H+. Recent studies have found a significant increase in urine uPA in patients with massive proteinuria.Urine uPA concentration were positively correlated with urinary protein and decreased with remission of proteinuria. In children and adults with nephrotic syndrome,as well as rat with proteinuria induced by puromycin amino-nucleoside, amiloride can inhibit uPA concentration in urine, which may be one of the mechanisms of amiloride in reducing proteinuria.
This study is a prospective , crossover, open-Label study. All patients need to be on an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) daily at least four weeks prior to the study. The baseline data would be recorded. Patients enrolled will receive either amiloride or hydrochlorothiazide first for 8 weeks.Hydrochlorothiazide, a similar diuretic as amiloride, but not inhibiting urokinase plasminogen activator receptor (uPAR), will be used as a control. Then the patients will discontinue amiloride or hydrochlorothiazide for a washout for 4 weeks, but continue with the ACE inhibitor or ARB. After that patients will cross over to receive another medication for another 8 weeks. We aim to evaluate the effect and safety of Amiloride in decreasing proteinuria for patients with chronic kidney disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Model Description
All patients need to be on an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) daily at least four weeks prior to the study. The baseline data would be recorded. Patients enrolled will receive either amiloride or hydrochlorothiazide first for 8 weeks.Then the patients will discontinue amiloride or hydrochlorothiazide for a washout for 4 weeks, but continue with ACEI(angiotensin-converting enzyme inhibitor ) or ARB. After that patients will cross over to receive another medication for another 8 weeks.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
amiloride
Arm Type
Experimental
Arm Description
Amiloride first for 8 weeks, then for a washout for 4 weeks, and cross over to receive hydrochlorothiazide for another 8 weeks
Arm Title
hydrochlorothiazide
Arm Type
Active Comparator
Arm Description
hydrochlorothiazide first for 8 weeks, then for a washout for 4 weeks, and cross over to receive amiloride for another 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Amiloride
Intervention Description
Amiloride first for 8 weeks, then for a washout for 4 weeks, and cross over to receive hydrochlorothiazide for another 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Hydrochlorothiazide
Intervention Description
hydrochlorothiazide first for 8 weeks, then for a washout for 4 weeks, and cross over to receive amiloride for another 8 weeks.
Primary Outcome Measure Information:
Title
The remission of proteinuria
Time Frame
after treatment for 12 weeks
Secondary Outcome Measure Information:
Title
estimated Glomerular Filtration Rate
Description
time to a 50% reduction in baseline estimated Glomerular filtration rate (according to CKD-EPI) and to doubling of baseline creatinine
Time Frame
after treatment for 12 weeks
Title
creatinine
Description
time to doubling of baseline creatinine
Time Frame
after treatment for 12 weeks
Title
hyperkalemia
Description
The ratio of hyperkalemia occurred at 12 weeks after treatment.
Time Frame
at 12 weeks after treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients at the age of more than 14 years old with chronic kidney disease
Good compliance of treatment
PCR≥500mg/g.cr ,more than double confirmed
Patients who written informed consent
Exclusion Criteria:
less than 14 years of age
eGFR≤30ml/min.1.73m2;
poor compliance of treatment
Previously intolerant or allergic to hydrochlorothiazide
Patients with history of gout within six months
Patients with active infection
Patients with severe cardiopulmonary disease and dysfunction of central nervous system
history of malignancy
life expectancy is less than 1 years
women who are pregnant,lactating and lack of contraception.
enrolled in other clinical trials within 3 months
patients who have used immunosuppressive agents or corticosteroids recently or in the past 12 weeks.
patients without informed consent written or who enable or unwilling to comply with protocol approved by researchers.
Facility Information:
Facility Name
Nephrology Dept,Guangdong General Hospital
City
Guangzhou
State/Province
Guangdong
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A New Application of Amiloride in the Treatment of Patient With Chronic Kidney Disease In Reducing Urinary PROtein
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