Beginning of Effective and Safe Treatment in Immunoglobulin A-1 Nephropathy-1 (BEST-IgAN-1)
Primary Purpose
Glomerulonephritis, Immunoglobulin A (IgA)
Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Losartan group
Placebo group
Sponsored by
About this trial
This is an interventional treatment trial for Glomerulonephritis, Immunoglobulin A (IgA) focused on measuring proteinuria, progression, early immunoglobulin A (IgA) nephropathy
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Losartan group
Placebo group
Arm Description
Losartan 50 mg daily
Placebo 1 pill daily which has same size, color and taste with losartan
Outcomes
Primary Outcome Measures
Significant proteinuria rate
Random urine protein-to-creatinine ratio >= 1g/g creatinine
Secondary Outcome Measures
Proteinuria remission rate
Random urine protein-to-creatinine ratio < 0.20 g/g creatinine
Impaired kidney function rate
estimated glomerular filtration rate decline >= 40% from the baseline value
Hypertension development rate
Systolic blood pressure >= 140 or diastolic blood pressure >= 90
Full Information
NCT ID
NCT03357653
First Posted
November 15, 2017
Last Updated
November 28, 2017
Sponsor
Ewha Womans University
Collaborators
The Catholic University of Korea, Kyung Hee University Hospital at Gangdong, Kyungpook National University Hospital, Korea University Guro Hospital, SMG-SNU Boramae Medical Center, Seoul National University Bundang Hospital, Seoul National University Hospital, Ajou University School of Medicine, Pusan National University Yangsan Hospital, Severance Hospital, Eulji General Hospital, National Health Insurance Service Ilsan Hospital, Chonnam National University Hospital, Chonbuk National University Hospital, Kangdong Sacred Heart Hospital, Hallym University Medical Center, Gangnam Severance Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03357653
Brief Title
Beginning of Effective and Safe Treatment in Immunoglobulin A-1 Nephropathy-1
Acronym
BEST-IgAN-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
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Unknown status
Study Start Date
January 30, 2018 (Anticipated)
Primary Completion Date
December 31, 2021 (Anticipated)
Study Completion Date
December 31, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ewha Womans University
Collaborators
The Catholic University of Korea, Kyung Hee University Hospital at Gangdong, Kyungpook National University Hospital, Korea University Guro Hospital, SMG-SNU Boramae Medical Center, Seoul National University Bundang Hospital, Seoul National University Hospital, Ajou University School of Medicine, Pusan National University Yangsan Hospital, Severance Hospital, Eulji General Hospital, National Health Insurance Service Ilsan Hospital, Chonnam National University Hospital, Chonbuk National University Hospital, Kangdong Sacred Heart Hospital, Hallym University Medical Center, Gangnam Severance Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glomerulonephritis, Immunoglobulin A (IgA)
Keywords
proteinuria, progression, early immunoglobulin A (IgA) nephropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
174 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Losartan group
Arm Type
Experimental
Arm Description
Losartan 50 mg daily
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
Placebo 1 pill daily which has same size, color and taste with losartan
Intervention Type
Drug
Intervention Name(s)
Losartan group
Other Intervention Name(s)
Losartan
Intervention Description
Losartan 50 mg daily
Intervention Type
Drug
Intervention Name(s)
Placebo group
Other Intervention Name(s)
Placebo
Intervention Description
Placebo 1 pill daily
Primary Outcome Measure Information:
Title
Significant proteinuria rate
Description
Random urine protein-to-creatinine ratio >= 1g/g creatinine
Time Frame
144 weeks after study started
Secondary Outcome Measure Information:
Title
Proteinuria remission rate
Description
Random urine protein-to-creatinine ratio < 0.20 g/g creatinine
Time Frame
48 weeks, 96 weeks, and 144 weeks after study started
Title
Impaired kidney function rate
Description
estimated glomerular filtration rate decline >= 40% from the baseline value
Time Frame
48 weeks, 96 weeks, and 144 weeks after study started
Title
Hypertension development rate
Description
Systolic blood pressure >= 140 or diastolic blood pressure >= 90
Time Frame
48 weeks, 96 weeks, and 144 weeks after study started
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dong-Ryeol Ryu, Professor
Phone
82-2-2650-2507
Email
drryu@ewha.ac.kr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dong-Ryeol Ryu, Professor
Organizational Affiliation
Ewha Womans University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
23331443
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.
Results Reference
background
PubMed Identifier
26874511
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.
Results Reference
background
PubMed Identifier
9631840
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.
Results Reference
background
PubMed Identifier
11007671
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.
Results Reference
background
PubMed Identifier
11331053
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.
Results Reference
background
PubMed Identifier
17596724
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.
Results Reference
background
PubMed Identifier
24946688
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.
Results Reference
background
Learn more about this trial
Beginning of Effective and Safe Treatment in Immunoglobulin A-1 Nephropathy-1
We'll reach out to this number within 24 hrs