Beginning of Effective and Safe Treatment in Immunoglobulin A-1 Nephropathy-1

Study Overview
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Brief Summary
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Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. IgAN is progressive, particularly when patients have a significant proteinuria (proteinuria >1g/g creatinine), impaired kidney function, or elevated blood pressure. In 10 years, nearly 20-40% of these IgAN patients progress to end-stage renal disease (ESRD). Early IgAN is tentatively defined when proteinuria is insignificant and kidney function and blood pressure are normal. Patients with early IgAN rarely progress to ESRD. However, 30-40% of patients with early IgAN ultimately developed a significant proteinuria and hypertension in 10 years. Therefore, earlier intervention may be needed if it can prevent the development of a significant proteinuria and hypertension. Since angiotensin ll receptor blocker (ARB) is drug of choice in reducing proteinuria and controlling blood pressure, the investigators hypothesized that early introduction of ARB may be beneficial in preventing the significant proteinuria development in early IgAN patients. To prove the hypothesis, the investigators plan the current interventional study.

Official Title
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A Randomized, Double Blinded, Placebo-controlled, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of Losartan in Early Immunoglobulin A Nephropathy (IgAN) Patients

Conditions
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Glomerulonephritis, Immunoglobulin A (IgA)

Intervention / Treatment
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* Drug: Losartan group
* Drug: Placebo group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-proven IgAN: dominant or co-dominant deposits of mesangial IgA in immunofluorescence stain Age >= 19 years Random urine protein-to-creatinine ratio 0.3 g/g creatinine to 1.0 g/g creatinine at visit 1 Estimated glomerular filtration rate >= 60 mL/min/1.73m2 at visit 1 People who voluntarily agreed to participate People who are compliant Exclusion Criteria: Prevalent Hypertension: systolic blood pressure >=140 mmHg and >=90 mmHg, previous physician diagnosis of hypertension, or taking anti-hypertensive drugs Prevalent Diabetes: fasting glucose >= 126 mg/dL, HbA1c >= 6.5%, taking insulin or anti-diabetic drugs, or previous physician diagnosis of diabetes Previous immunosuppressive drugs use to treat IgAN Secondary IgAN Renin-angiotensin-aldosterone inhibitors (RASI) dependent patients (congestive heart failure, ischemic heart disease, and others) hypersensitivity to RASI Other chronic diseases: malignancy within 5 years, significant liver and gastrointestinal disease and other autoimmune disease Pregnancy symptomatic orthostatic hypotension People who already participated in other interventional studies or taking interventional drugs within 3 month of screening visit Inappropriate people ascertained by investigator

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The investigators will test the effect of ARB to prevent the development of significant proteinuria, defined as random urine protein-to-creatinine ratio of >1g/g creatinine. In this study, the investigators choose losartan as a testing ARB. The investigators will compare the rate of significant proteinuria development between 2 arms, namely losartan group and placebo group after 144 weeks' treatment.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Losartan group<br>Losartan 50 mg daily | Drug: Losartan group<br>* Losartan 50 mg daily<br>* Other names: Losartan;|
| Placebo Comparator: Placebo group<br>Placebo 1 pill daily which has same size, color and taste with losartan | Drug: Placebo group<br>* Placebo 1 pill daily<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Significant proteinuria rate | Random urine protein-to-creatinine ratio >= 1g/g creatinine | 144 weeks after study started | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proteinuria remission rate | Random urine protein-to-creatinine ratio < 0.20 g/g creatinine | 48 weeks, 96 weeks, and 144 weeks after study started | 
| Impaired kidney function rate | estimated glomerular filtration rate decline >= 40% from the baseline value | 48 weeks, 96 weeks, and 144 weeks after study started | 
| Hypertension development rate | Systolic blood pressure >= 140 or diastolic blood pressure >= 90 | 48 weeks, 96 weeks, and 144 weeks after study started | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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proteinuria, progression, early immunoglobulin A (IgA) nephropathy