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

NCT03357653 | Unknown Phase 3 DMC

• 1 other identifier: BEST-IGAN-001
• Study Type: interventional
• Target: 174
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Glomerulonephritis, Immunoglobulin A (IgA)

Keywords

proteinuria; progression; early immunoglobulin A (IgA) nephropathy

Outcome Measures

Primary Outcomes (1)

• Significant proteinuria rate

  Random urine protein-to-creatinine ratio \>= 1g/g creatinine

  144 weeks after study started

Secondary Outcomes (3)

• Proteinuria remission rate

  48 weeks, 96 weeks, and 144 weeks after study started

• Impaired kidney function rate

  48 weeks, 96 weeks, and 144 weeks after study started

• Hypertension development rate

  48 weeks, 96 weeks, and 144 weeks after study started

Study Arms (2)

Losartan group

EXPERIMENTAL

Losartan 50 mg daily

Drug: Losartan group

Placebo group

PLACEBO COMPARATOR

Placebo 1 pill daily which has same size, color and taste with losartan

Drug: Placebo group

Interventions

Losartan group DRUG

Losartan 50 mg daily

Also known as: Losartan

Losartan group

Placebo group DRUG

Placebo 1 pill daily

Also known as: Placebo

Placebo group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ewha Womans University: lead
• The Catholic University of Korea: collaborator
• Kyung Hee University Hospital at Gangdong: collaborator
• Kyungpook National University Hospital: collaborator
• Korea University Guro Hospital: collaborator
• SMG-SNU Boramae Medical Center: collaborator
• Seoul National University Bundang Hospital: collaborator
• Seoul National University Hospital: collaborator
• Ajou University School of Medicine: collaborator
• Pusan National University Yangsan Hospital: collaborator
• Severance Hospital: collaborator
• Eulji General Hospital: collaborator
• National Health Insurance Service Ilsan Hospital: collaborator
• Chonnam National University Hospital: collaborator
• Chonbuk National University Hospital: collaborator
• Kangdong Sacred Heart Hospital: collaborator
• Hallym University Medical Center: collaborator
• Gangnam Severance Hospital: collaborator

Related Publications (8)

• 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.

  PMID: 23331443 BACKGROUND

• 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.

  PMID: 26874511 BACKGROUND

• 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.

  PMID: 9631840 BACKGROUND

• 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.

  PMID: 11007671 BACKGROUND

• 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.

  PMID: 11331053 BACKGROUND

• 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.

  PMID: 17596724 BACKGROUND

• 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.

  PMID: 24946688 BACKGROUND

• Tunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.pub3.

  PMID: 38299639 DERIVED

MeSH Terms

Conditions

Glomerulonephritis; Proteinuria; Disease Progression; Kidney Diseases

Interventions

Losartan

Condition Hierarchy (Ancestors)

Nephritis; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Dong-Ryeol Ryu, Professor

  Ewha Womans University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dong-Ryeol Ryu, Professor

CONTACT

82-2-2650-2507; drryu@ewha.ac.kr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 15, 2017
• First Posted: November 30, 2017
• Study Start: January 30, 2018
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: November 30, 2017

Record last verified: 2017-11