Clinical trial NCT03357653: Beginning of Effective and Safe Treatment in Immunoglobulin A-1 Nephropathy-1
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Glomerulonephritis, Immunoglobulin A (IgA)
Keywords: proteinuria
progression
early immunoglobulin A (IgA) nephropathy
Lead sponsor: Ewha Womans University
Sponsor class: OTHER
Collaborators: name: The Catholic University of Korea
name: Kyung Hee University Hospital at Gangdong
name: Kyungpook National University Hospital
name: Korea University Guro Hospital
name: SMG-SNU Boramae Medical Center
name: Seoul National University Bundang Hospital
name: Seoul National University Hospital
name: Ajou University School of Medicine
name: Pusan National University Yangsan Hospital
name: Severance Hospital
name: Eulji General Hospital
name: National Health Insurance Service Ilsan Hospital
name: Chonnam National University Hospital
name: Chonbuk National University Hospital
name: Kangdong Sacred Heart Hospital
name: Hallym University Medical Center
name: Gangnam Severance Hospital
First posted: 2017-11-30
Enrollment: 174
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Biopsy-proven IgAN: dominant or co-dominant deposits of mesangial IgA in immunofluorescence stain
2. Age \>= 19 years
3. Random urine protein-to-creatinine ratio 0.3 g/g creatinine to 1.0 g/g creatinine at visit 1
4. Estimated glomerular filtration rate \>= 60 mL/min/1.73m2 at visit 1
5. People who voluntarily agreed to participate
6. People who are compliant

Exclusion Criteria:

1. Prevalent Hypertension: systolic blood pressure \>=140 mmHg and \>=90 mmHg, previous physician diagnosis of hypertension, or taking anti-hypertensive drugs
2. Prevalent Diabetes: fasting glucose \>= 126 mg/dL, HbA1c \>= 6.5%, taking insulin or anti-diabetic drugs, or previous physician diagnosis of diabetes
3. Previous immunosuppressive drugs use to treat IgAN
4. Secondary IgAN
5. Renin-angiotensin-aldosterone inhibitors (RASI) dependent patients (congestive heart failure, ischemic heart disease, and others)
6. hypersensitivity to RASI
7. Other chronic diseases: malignancy within 5 years, significant liver and gastrointestinal disease and other autoimmune disease
8. Pregnancy
9. symptomatic orthostatic hypotension
10. People who already participated in other interventional studies or taking interventional drugs within 3 month of screening visit
11. Inappropriate people ascertained by investigator

Primary outcomes:
measure: Significant proteinuria rate
timeFrame: 144 weeks after study started
Secondary outcomes:
measure: Proteinuria remission rate
timeFrame: 48 weeks, 96 weeks, and 144 weeks after study started
measure: Impaired kidney function rate
timeFrame: 48 weeks, 96 weeks, and 144 weeks after study started
measure: Hypertension development rate
timeFrame: 48 weeks, 96 weeks, and 144 weeks after study started
Other outcomes:
Locations:
Study officials:
affiliation: Ewha Womans University
name: Dong-Ryeol Ryu, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li PK, Kwan BC, Chow KM, Leung CB, Szeto CC. Treatment of early immunoglobulin A nephropathy by angiotensin-converting enzyme inhibitor. Am J Med. 2013 Feb;126(2):162-8. doi: 10.1016/j.amjmed.2012.06.028.
citation: Jo YI, Na HY, Moon JY, Han SW, Yang DH, Lee SH, Park HC, Choi HY, Lim SD, Kie JH, Lee YK, Shin SK. Effect of low-dose valsartan on proteinuria in normotensive immunoglobulin A nephropathy with minimal proteinuria: a randomized trial. Korean J Intern Med. 2016 Mar;31(2):335-43. doi: 10.3904/kjim.2014.266. Epub 2016 Feb 15.
citation: Nieuwhof C, Kruytzer M, Frederiks P, van Breda Vriesman PJ. Chronicity index and mesangial IgG deposition are risk factors for hypertension and renal failure in early IgA nephropathy. Am J Kidney Dis. 1998 Jun;31(6):962-70. doi: 10.1053/ajkd.1998.v31.pm9631840.
citation: Lai FM, Szeto CC, Choi PC, Li PK, Chan AW, Tang NL, Lui SF, Wang AY, To KF. Characterization of early IgA nephropathy. Am J Kidney Dis. 2000 Oct;36(4):703-8. doi: 10.1053/ajkd.2000.17614.
citation: Szeto CC, Lai FM, To KF, Wong TY, Chow KM, Choi PC, Lui SF, Li PK. The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria. Am J Med. 2001 Apr 15;110(6):434-7. doi: 10.1016/s0002-9343(01)00659-3.
citation: Shen P, He L, Li Y, Wang Y, Chan M. Natural history and prognostic factors of IgA nephropathy presented with isolated microscopic hematuria in Chinese patients. Nephron Clin Pract. 2007;106(4):c157-61. doi: 10.1159/000104426. Epub 2007 Jun 26.
citation: Lee H, Hwang JH, Paik JH, Ryu HJ, Kim DK, Chin HJ, Oh YK, Joo KW, Lim CS, Kim YS, Lee JP. Long-term prognosis of clinically early IgA nephropathy is not always favorable. BMC Nephrol. 2014 Jun 19;15:94. doi: 10.1186/1471-2369-15-94.