Steroids Therapy in IgA Nephropathy With Crescents

IgA Nephropathy Clinical Trial

Official title:

Effect and Security of Steroids Therapy for Patients of IgA Nephropathy With Crescents : A Prospective, Randomized, Controlled, Multi-Center Clinical Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04833374
• Other study ID #: 1010PY (2020) -51
• Status: Recruiting
• Phase: Phase 3
• Start date: May 24, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: June 2021
• Source: Sixth Affiliated Hospital, Sun Yat-sen University
• Contact: Mengjun Liang, MM
• Phone: 86-020-38379727
• Email: liangmj7[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This prospective, randomized, controlled, multi-center clinical trial will evaluate the effect and security of steroids therapy for patients of IgA nephropathy with crescents.

Description:

It has been reported that for urinary protein excretion that is persistently more than 1g/24h and eGFR>50ml/min/1.73m2 in IgA nephropathy(IgAN), the KDIGO guidelines suggest a 6-month course of glucocorticoids. The famous study by Pozzi C has proved that for patients of IgAN with proteinuria of 1.0-3.5g/24h and serum creatinine concentrations of 133 umol/L or less, a 6-month course of steroid treatment(1g/d methylprednisolone intravenously for 3 consecutive days, with the course repeated 2 months and 4 months later,then oral prednisone 0.5mg/kg/d on alternate days for 6 months) could significantly reduce proteinuria and protect against renal function deterioration in IgAN. However, according to Oxford classification, crescents in IgAN would effect the prognosis.This will be a prospective, randomized, controlled, multi-center study. Patients in treatment group will receive 0.5g/d methylprednisolone intravenously for 3 consecutive days in the 1st-2nd-3rd month ,then oral prednisone 0.5mg/kg/d on alternate days. Patients in control group will receive 0.5g/d methylprednisolone intravenously for 3 consecutive days in the 1st-3rd-5th month ,then oral prednisone 0.5mg/kg/d on alternate days. After followed-up for 6 months, the curative effect of steroid therapy on proteinuria and the progression of IgAN will be evaluated.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Age 14~65 years, regardless of gender

2. Clinical evaluation and renal biopsy diagnostic for IgA nephropathy, presenting with crescents.

3. Average urinary protein excretion of 0.3~3.5g/24h on two successive examinations.

4. eGFR=30 ml/min/1.73m2.

5. Willingness to sign an informed consent.

Exclusion Criteria:

1. Secondary IgAN such as systemic lupus erythematosus, Henoch-Schonlein purpuric nephritis and hepatitis B-associated nephritis, etc.

2. Rapidly progressive nephritic syndrome (crescent formation=50%).

3. Acute renal failure, including rapidly progressive IgAN.

4. Current or recent (within 30 days) exposure to high-dose of steroids or immunosuppressive therapy (CTX?MMF?CsA?FK506).

5. Date of renal biopsy exceeds more than 30 days.

6. Cirrhosis, chronic active liver disease, and serious liver function damage.

7. History of significant gastrointestinal disorders (e.g. severe chronic diarrhea or active peptic ulcer disease).

8. Any Active systemic infection or history of serious infection within one month.

9. Other major organ system disease (e.g. serious cardiovascular diseases including congestive heart failure , chronic obstructive pulmonary disease, asthma requiring oral steroid treatment or central nervous system diseases).

10. Active tuberculosis

11. Malignant hypertension that is difficult to be controlled by oral drugs.

12. Known allergy, contraindication or intolerance to the steroids.

13. Pregnancy or breast feeding at the time of entry or unwillingness to comply with measures for contraception.

14. Malignant tumors.

15. Excessive drinking or drug abuse.

16. Mental aberrations.

17. Current or recent (within 30 days) exposure to any other investigational drugs.

18. Current use of RAS inhibitors needs to be eluted for at least 1 week before participating in the study.

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IgA Nephropathy
• Kidney Diseases

Intervention

Drug:
• Methylprednisolone
Patients will receive 0.5g/d methylprednisolone intravenously for 3 consecutive days in the 1st-2nd-3rd or 1st-3rd-5th month, then oral prednisone 0.5mg/kg/d on alternate days for 6 months.

Locations

Country	Name	City	State
China	Sixth Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sixth Affiliated Hospital, Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (8)

Hotta O, Furuta T, Chiba S, Tomioka S, Taguma Y. Regression of IgA nephropathy: a repeat biopsy study. Am J Kidney Dis. 2002 Mar;39(3):493-502. — View Citation

Lv J, Zhang H, Wong MG, Jardine MJ, Hladunewich M, Jha V, Monaghan H, Zhao M, Barbour S, Reich H, Cattran D, Glassock R, Levin A, Wheeler D, Woodward M, Billot L, Chan TM, Liu ZH, Johnson DW, Cass A, Feehally J, Floege J, Remuzzi G, Wu Y, Agarwal R, Wang — View Citation

Pozzi C, Andrulli S, Del Vecchio L, Melis P, Fogazzi GB, Altieri P, Ponticelli C, Locatelli F. Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol. 2004 Jan;15(1):157-63. — View Citation

Pozzi C, Bolasco PG, Fogazzi GB, Andrulli S, Altieri P, Ponticelli C, Locatelli F. Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet. 1999 Mar 13;353(9156):883-7. — View Citation

Rauen T, Eitner F, Fitzner C, Sommerer C, Zeier M, Otte B, Panzer U, Peters H, Benck U, Mertens PR, Kuhlmann U, Witzke O, Gross O, Vielhauer V, Mann JF, Hilgers RD, Floege J; STOP-IgAN Investigators. Intensive Supportive Care plus Immunosuppression in IgA — View Citation

Shoji T, Nakanishi I, Suzuki A, Hayashi T, Togawa M, Okada N, Imai E, Hori M, Tsubakihara Y. Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephro — View Citation

Trimarchi H, Barratt J, Cattran DC, Cook HT, Coppo R, Haas M, Liu ZH, Roberts IS, Yuzawa Y, Zhang H, Feehally J; IgAN Classification Working Group of the International IgA Nephropathy Network and the Renal Pathology Society; Conference Participants. Oxfor — View Citation

Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med. 2013 Jun 20;368(25):2402-14. doi: 10.1056/NEJMra1206793. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission of proteinuria	Proteinuria<0.3g/24h and stable renal function	6 months
Secondary	Partial remission of proteinuria	Proteinuria decline>50%, serum albumin>30g/L and stable renal function	6 months
Secondary	Deterioration of renal function	The longitudinal decline of eGFR, serum creatinine arise>50%, or eGFR decline>25%, or onset of end-stage renal disease or dialysis treatment, or kidney transplantation	6 months