A Controlled Study of Steroids Therapy for Patients of IgA Nephropathy With Active Pathological Changes.

Phase 2

• Conditions: Glomerulonephritis, IGA; Steroid Nephropathy; Necrosis; Peripapillary Crescent
• Interventions: Drug: Methylprednisolone(intravenously in the 1st-2nd-3rd month ); Drug: Methylprednisolone(intravenously in the 1st-3rd-5th month)

• Registration Number: NCT02160132
• Lead Sponsor: Sun Yat-sen University

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 active pathological changes,including crescents,necrosis and microthrombus.

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. Furthermore, as we know, active pathological changes in IgAN,including crescents,necrosis and microthrombus,which may turn fibrosis after three months 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 methylprednisolone 0.4mg/kg/d on consecutive days Patients in control group will receive 0.5g/d methylprednisolone intravenously for 3 consecutive days in the 1st-3rd-5th month ,then oral methylprednisolone 0.4mg/kg/d on consecutive days. After followed-up for 6 months, the curative effect of steroid therapy on proteinuria and the progression of IgAN will be evaluated.

Study Timeline

• Study Start: 2014-06
• Study First Submitted: 2014-06-03
• Study First Submitted QC: 2014-06-06
• Study First Posted: 2014-06-10
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-02
• Last Update Posted: 2015-03-03
• Primary Completion: 2016-12
• Study Completion: 2016-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

• Age 14~65 years, regardless of gender
• Clinical evaluation and renal biopsy diagnostic for IgA nephropathy, presenting with active pathological changes,including cellular crescents,necrosis and microthrombus.
• Average urinary protein excretion of 0.5~3.5g/24h on two successive examinations.
• eGFR ≥ 50 ml/min/1.73 m2
• Willingness to sign an informed consent.

Exclusion Criteria

• Secondary IgAN such as systemic lupus erythematosus, Henoch-Schonlein purpuric nephritis and hepatitis B -associated nephritis.
• Rapidly progressive nephritic syndrome (crescent formation≥50%).
• Acute renal failure, including rapidly progressive IgAN.
• Current or recent (within 30 days) exposure to high-dose of steroids or immunosuppressive therapy (CTX、MMF、CsA、FK506).
• Date of renal biopsy exceeds more than 30 days.
• Cirrhosis, chronic active liver disease.
• History of significant gastrointestinal disorders (e.g. severe chronic diarrhea or active peptic ulcer disease).
• Any Active systemic infection or history of serious infection within one month.
• 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).
• Active tuberculosis
• Malignant hypertension that is difficult to be controlled by oral drugs.
• Known allergy, contraindication or intolerance to the steroids.
• Pregnancy or breast feeding at the time of entry or unwillingness to comply with measures for contraception.
• Malignant tumors
• Excessive drinking or drug abuse
• Mental aberrations
• Current or recent (within 30 days) exposure to any other investigational drugs.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A 1-2-3Group	Methylprednisolone(intravenously in the 1st-2nd-3rd month )	Methylprednisolone 0.5g/d intravenously for 3 consecutive days in the 1st-2nd-3rd month ,and oral methylprednisolone 0.4mg/kg/d on consecutive days for 6 months.
B 1-3-5Group	Methylprednisolone(intravenously in the 1st-3rd-5th month)	Methylprednisolone 0.5g/d intravenously for 3 consecutive days in the 1st-3rd-5th month ,and oral methylprednisolone 0.4mg/kg/d on consecutive days for 6 months.

Primary Outcome Measures

Name	Time	Method
Remission of proteinuria (complete or partial)	up to 6 months

Secondary Outcome Measures

Name	Time	Method
Deterioration of renal function (evidenced by a 50% rise from baseline serum creatinine (SCr) levels, or a 25% decline from baseline eGFR levels, or onset of end-stage renal disease or dialysis treatment, or kidney transplantation).	up to 6 months
The longitudinal decline of kidney function(eGFR)	up to 6 months

Trial Locations

Locations (6)

Department of Nephrology, 2nd Affiliated Hospital,Guangzhou Medical University; 🇨🇳 Guangzhou, Guangdong, China

Department of Nephrology,Dongguan People's Hospital; 🇨🇳 Dongguan, Guangdong, China

Department of Nephrology, 6th Affiliated Hospital, Sun Yat-Sen University; 🇨🇳 Guangzhou, Guangdong, China

Department of Nephrology,Huizhou Municipal Central Hospital; 🇨🇳 Huizhou, Guangdong, China

Department of Nephrology,1st Affiliated Hospital,Shenzhen University; 🇨🇳 Shenzhen, Guangdong, China

Department of Nephrology,1st People's Hospital of Zhaoqing; 🇨🇳 Zhaoqing, Guangdong, China