Trial of Plasma Exchange for Severe Crescentic IgA Nephropathy

Study Overview
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Brief Summary
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Crescentic IgA nephropathy (CreIgAN) has a poor prognosis despite aggressive immunosuppressive therapy. The efficacy of plasma exchange (PE) in CreIgAN is not well defined. This study will evaluate the efficacy and safety of plasma exchange as adjunctive therapy for severe crescentic IgA nephropathy compared to pulse methylprednisolone on a background of oral prednisolone and cyclophosphamide in prevent kidney failure.

Detailed Description
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IgA nephropathy (IgAN) is one of the most common glomerulonephritides and is characterized by a highly variable clinical course and diverse histopathological lesions. Although most affected individuals develop chronic, slowly progressive renal injury, a subgroup of patients (<5% of all IgAN patients) with diffuse crescent formation, which is termed as crescentic IgA nephropathy (CreIgAN) and often leads to rapidly progressive kidney failure. The recent Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest high-dose steroids and cyclophosphamide therapy for CreIgAN. However, this suggestion is mainly based on several small observational studies, and the 1- and 5-year renal survival rates of patients treated with this regimen were as low as 65% and 28%, respectively, in one large cohort of CreIgAN patients. The efficacy of plasma exchange (PE) in severe CreIgAN is not well evaluated, although several anecdotal reports have indicated benefit of PE in combination with immunosuppressive therapies in IgAN patients. Retrospective cohort study in our unite also supported the benefit of PE as additional therapy for CreIgAN patients. However, randomized controlled trial is needed to evaluate the efficacy and safety of plasma exchange as adjunctive therapy for crescentic IgA nephropathy compared to pulse methylprednisolone on a background of oral prednisolone and cyclophosphamide in prevent kidney failure.

Official Title
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Randomized Trial of Plasma Exchange as Adjunctive Therapy for Severe Crescentic GlomerUlonephritis of IgA NEphropathy (RESCUE Study)

Conditions
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Glomerulonephritis, IGA, Kidney Diseases, Acute Renal Insufficiency, Rapidly Progressive Glomerulonephritis

Intervention / Treatment
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* Procedure: Plasma Exchange (PE)
* Drug: Methylprednisolone pulse


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-proven within 3ws Primary IgAN or Henoch-Schönlein Purpura nephritis of crescent >50%(>8 glomeruli) Serum creatinine ≥ 200 μmol/l， rapidly deterioration of renal function Exclusion Criteria: <14 or >65 years old With high Scr requiring dialysis for≥ 3w Scr>200μmol/L ≥1 yr before entry Main of old crescent ; Fibrous crescent>50% Anti-glomerular basement membrane (GBM) or antineutrophil cytoplasmic antibody (ANCA) antibody positive Women in gestational and lactational period With diabetes or uncontrollable malignant hypertension or Thrombotic Microangiopathy With Malignancy Chronic active infection including HBV hepatitis C virus (HCV) HIV or active tuberculosis Other autoimmune disease A second clearly defined cause of renal failure Contraindication of plasma exchange treatment or steroid pulse Patients who are unlikely to comply with the study protocol in the view of the treating physician.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PE and methylprednisolone pulse<br>Plasma exchange(PE) and methylprednisolone pulse therapy: plasma exchange >7 within 3ws, Volume: 60ml/kg/course; Replacement fluid: 5% albumin or fresh frozen plasma and methylprednisolone pulse therapy Basic treatment: Oral prednisone was tapered from 1 mg/kg/d for 6wks, then diminish 5mg/d every 10d, stop at the sixth month; cyclophosphamide 1.5 mg/kg/d for 3 months, 50mg /d at 3 months and stopped at 6 month. | Procedure: Plasma Exchange (PE)<br>* PE treatment>7 within 3weeks; Volume exchanged: 60ml/kg/course; Replacement fluid: 5% Albumin or fresh frozen plasma; PE was performed by dialysis machine (IQ-21, Asahi Japan) and plasma separator (OP- 08W, Asahi Japan)<br>* Other names: Plasmapheresis;Drug: Methylprednisolone pulse<br>* methylprednisolone 7-15mg/kg/d 3 times, Qd. or Qod<br>* Other names: Intensive Immunosuppressive treatment;|
| Active Comparator: Methylprednisolone pulse<br>Methylprednisolone pulse alone: methylprednisolone 7-15mg/kg/d 3 times on consecutive or alternate days Basic treatment: Oral prednisone was tapered from 1 mg/kg/d for 6wks, then diminish 5mg/d every 10d, stop at the sixth month; cyclophosphamide 1.5 mg/kg/d for 3 months, 50mg /d at 3 months and stopped at 6 month. | Drug: Methylprednisolone pulse<br>* methylprednisolone 7-15mg/kg/d 3 times, Qd. or Qod<br>* Other names: Intensive Immunosuppressive treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| End-stage renal disease or death | End-stage renal disease: defined as a need for maintenance dialysis > 6 months; or need kidney transplantation , and death; during follow-up. | 12 months after final subject is enrolled | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal remission | Renal remission: defined as the independent of dialysis, or serum creatinine under 200μmol/l within 6 months, and lasts without a first relapse until at least 12 months after randomization | 12 months after final subject is enrolled | 
| Proteinuria remission | Proteinuria remission: defined as proteinuria < 0.5g/d for ≥3months | At the 12th month and 36th month after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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crescentic IgA nephropathy, plasma exchange treatment or plasmapheresis, randomized controlled trial, intensive immunosuppressive treatment, methylprednisolone pulse