Trial of Plasma Exchange for Severe Crescentic IgA Nephropathy

Phase 2

Terminated

• Conditions: Glomerulonephritis, IGA; Kidney Diseases; Acute Renal Insufficiency; Rapidly Progressive Glomerulonephritis
• Interventions: Procedure: Plasma Exchange (PE); Drug: Methylprednisolone pulse

• Registration Number: NCT02647255
• Lead Sponsor: Peking University First Hospital

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.

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 Timeline

• Study First Submitted: 2015-12-21
• Study First Submitted QC: 2016-01-04
• Study First Posted: 2016-01-06
• Study Start: 2016-03
• Primary Completion: 2020-10
• Study Completion: 2020-10
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-30
• Last Update Posted: 2021-10-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Biopsy-proven within 3ws
2. Primary IgAN or Henoch-Schönlein Purpura nephritis of crescent >50%(>8 glomeruli)
3. Serum creatinine ≥ 200 μmol/l， rapidly deterioration of renal function

Exclusion Criteria

1. <14 or >65 years old
2. With high Scr requiring dialysis for≥ 3w
3. Scr>200μmol/L ≥1 yr before entry
4. Main of old crescent ; Fibrous crescent>50%
5. Anti-glomerular basement membrane (GBM) or antineutrophil cytoplasmic antibody (ANCA) antibody positive
6. Women in gestational and lactational period
7. With diabetes or uncontrollable malignant hypertension or Thrombotic Microangiopathy
8. With Malignancy
9. Chronic active infection including HBV hepatitis C virus (HCV) HIV or active tuberculosis
10. Other autoimmune disease
11. A second clearly defined cause of renal failure
12. Contraindication of plasma exchange treatment or steroid pulse
13. Patients who are unlikely to comply with the study protocol in the view of the treating physician.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PE and methylprednisolone pulse	Plasma Exchange (PE)	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.
PE and methylprednisolone pulse	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.
Methylprednisolone pulse	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (2)

Renal Division, Department of Medicine, Peking University First Hospital; 🇨🇳 Beijing, Beijing, China

Renal division, Peking University First Hospital; 🇨🇳 Beijing, Beijing, China