Glomerulonephritis, Immunoglobulin A (IgA) Clinical Trial
— BEST-IgAN-1Official 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
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.
| Status | Not yet recruiting |
| Enrollment | 174 |
| Est. completion date | December 31, 2021 |
| Est. primary completion date | December 31, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 19 Years and older |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| Ewha Womans University | Ajou University School of Medicine, Chonbuk National University Hospital, Chonnam National University Hospital, Eulji General Hospital, Gangnam Severance Hospital, Hallym University Medical Center, Kangdong Sacred Heart Hospital, Korea University Guro Hospital, Kyung Hee University Hospital at Gangdong, Kyungpook National University, National Health Insurance Service Ilsan Hospital, Pusan National University Yangsan Hospital, Seoul National University Bundang Hospital, Seoul National University Hospital, Severance Hospital, SMG-SNU Boramae Medical Center, The Catholic University of Korea |
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. — View 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. — View 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. — View 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. — View 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. — View 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. Epub 2007 Jun 26. — View 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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Significant proteinuria rate | Random urine protein-to-creatinine ratio >= 1g/g creatinine | 144 weeks after study started | |
| Secondary | Proteinuria remission rate | Random urine protein-to-creatinine ratio < 0.20 g/g creatinine | 48 weeks, 96 weeks, and 144 weeks after study started | |
| Secondary | Impaired kidney function rate | estimated glomerular filtration rate decline >= 40% from the baseline value | 48 weeks, 96 weeks, and 144 weeks after study started | |
| Secondary | Hypertension development rate | Systolic blood pressure >= 140 or diastolic blood pressure >= 90 | 48 weeks, 96 weeks, and 144 weeks after study started |