Clinical trial NCT04833374: Steroids Therapy in IgA Nephropathy With Crescents
Official title: Effect and Security of Steroids Therapy for Patients of IgA Nephropathy With Crescents : A Prospective, Randomized, Controlled, Multi-Center Clinical Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: IgA Nephropathy
Keywords: IgA nephropathy
crescent
steroid
proteinuria
eGFR
Lead sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
Sponsor class: OTHER
First posted: 2021-04-06
Enrollment: 200
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Complete remission of proteinuria
timeFrame: 6 months
Secondary outcomes:
measure: Partial remission of proteinuria
timeFrame: 6 months
measure: Deterioration of renal function
timeFrame: 6 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sixth Affiliated Hospital, Sun Yat-sen University
state: Guangdong
Study officials:
References:
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. doi: 10.1016/s0140-6736(98)03563-6.
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. doi: 10.1097/01.asn.0000103869.08096.4f.
citation: Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med. 2013 Jun 20;368(25):2402-14. doi: 10.1056/NEJMra1206793. No abstract available.
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. Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group. Kidney Int. 2017 May;91(5):1014-1021. doi: 10.1016/j.kint.2017.02.003. Epub 2017 Mar 22.
citation: 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. doi: 10.1053/ajkd.2002.31399.
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 nephropathy. Am J Kidney Dis. 2000 Feb;35(2):194-201. doi: 10.1016/s0272-6386(00)70326-x.
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 Nephropathy. N Engl J Med. 2015 Dec 3;373(23):2225-36. doi: 10.1056/NEJMoa1415463.
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 HY, Perkovic V; TESTING Study Group. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017 Aug 1;318(5):432-442. doi: 10.1001/jama.2017.9362.