RESCUE: Trial of Plasma Exchange for Severe Crescentic IgA Nephropathy
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PE and methylprednisolone pulse 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)
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)
Other Names:
Drug: Methylprednisolone pulse
methylprednisolone 7-15mg/kg/d 3 times, Qd. or Qod
Other Names:
|
| Active Comparator: Methylprednisolone pulse 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
methylprednisolone 7-15mg/kg/d 3 times, Qd. or Qod
Other Names:
|
Outcome Measures
Primary Outcome Measures
- End-stage renal disease or death [12 months after final subject is enrolled]
End-stage renal disease: defined as a need for maintenance dialysis > 6 months; or need kidney transplantation , and death; during follow-up.
Secondary Outcome Measures
- Renal remission [12 months after final subject is enrolled]
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
- Proteinuria remission [At the 12th month and 36th month after randomization]
Proteinuria remission: defined as proteinuria < 0.5g/d for ≥3months
Other Outcome Measures
- Rate of serious adverse events [From 12 months after first subject enrolled to 12 months after final subject is enrolled]
Serious adverse events are defined as: Clinically apparent gastrointestinal haemorrhage requiring hospitalization or prolonging the time of hospitalization. Serious infections requiring hospitalization or prolonging the time of hospitalization. Severe allergic reaction requiring hospitalization or prolonging the time of hospitalization. Chronic viral infection, including HIV hepatitis B virus(HBV) and HCV Other adverse events
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Biopsy-proven within 3ws
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Primary IgAN or Henoch-Schönlein Purpura nephritis of crescent >50%(>8 glomeruli)
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Serum creatinine ≥ 200 μmol/l， rapidly deterioration of renal function
Exclusion Criteria:
-
<14 or >65 years old
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With high Scr requiring dialysis for≥ 3w
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Scr>200μmol/L ≥1 yr before entry
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Main of old crescent ; Fibrous crescent>50%
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Anti-glomerular basement membrane (GBM) or antineutrophil cytoplasmic antibody (ANCA) antibody positive
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Women in gestational and lactational period
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With diabetes or uncontrollable malignant hypertension or Thrombotic Microangiopathy
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With Malignancy
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Chronic active infection including HBV hepatitis C virus (HCV) HIV or active tuberculosis
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Other autoimmune disease
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A second clearly defined cause of renal failure
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Contraindication of plasma exchange treatment or steroid pulse
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Patients who are unlikely to comply with the study protocol in the view of the treating physician.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Renal Division, Department of Medicine, Peking University First Hospital | Beijing | Beijing | China | 100034 |
| 2 | Renal division, Peking University First Hospital | Beijing | Beijing | China | 100034 |
Sponsors and Collaborators
- Peking University First Hospital
Investigators
- Study Director: Hong Zhang, MD, PHD, Renal Division, Department of Medicine, Peking University First Hospital;Peking University Institute of Nephrology
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
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- Fujinaga S, Ohtomo Y, Umino D, Mochizuki H, Murakami H, Shimizu T, Yamashiro Y, Kaneko K. Plasma exchange combined with immunosuppressive treatment in a child with rapidly progressive IgA nephropathy. Pediatr Nephrol. 2007 Jun;22(6):899-902. Epub 2007 Feb 7.
- Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, Mirapeix E, Savage CO, Sinico RA, Stegeman CA, Westman KW, van der Woude FJ, de Lind van Wijngaarden RA, Pusey CD; European Vasculitis Study Group. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007 Jul;18(7):2180-8. Epub 2007 Jun 20.
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- Tang Z, Wu Y, Wang QW, Yu YS, Hu WX, Yao XD, Chen HP, Liu ZH, Li LS. Idiopathic IgA nephropathy with diffuse crescent formation. Am J Nephrol. 2002 Sep-Dec;22(5-6):480-6.
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