Trial of Plasma Exchange for Severe Crescentic IgA Nephropathy

Kidney Diseases Clinical Trial

— RESCUE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02647255
• Other study ID #: RESCUE
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: March 2016
• Est. completion date: October 2020

Study information

• Verified date: September 2021
• Source: Peking University First Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: October 2020
• Est. primary completion date: October 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute Renal Insufficiency
• Glomerulonephritis
• Glomerulonephritis, IGA
• Kidney Diseases
• Rapidly Progressive Glomerulonephritis
• Renal Insufficiency

Intervention

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)

Drug:
• Methylprednisolone pulse
methylprednisolone 7-15mg/kg/d 3 times, Qd. or Qod

Locations

Country	Name	City	State
China	Renal Division, Department of Medicine, Peking University First Hospital	Beijing	Beijing
China	Renal division, Peking University First Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University First Hospital

Country where clinical trial is conducted

China, 

References & Publications (13)

Abe T, Kida H, Yoshimura M, Yokoyama H, Koshino Y, Tomosugi N, Hattori N. Participation of extracapillary lesions (ECL) in progression of IgA nephropathy. Clin Nephrol. 1986 Jan;25(1):37-41. — View Citation

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. — View Citation

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. — View Citation

Lai KN, Lai FM, Leung AC, Ho CP, Vallance-Owen J. Plasma exchange in patients with rapidly progressive idiopathic IgA nephropathy: a report of two cases and review of literature. Am J Kidney Dis. 1987 Jul;10(1):66-70. Review. — View Citation

Lv J, Yang Y, Zhang H, Chen W, Pan X, Guo Z, Wang C, Li S, Zhang J, Zhang J, Liu L, Shi S, Wang S, Chen M, Cui Z, Chen N, Yu X, Zhao M, Wang H. Prediction of outcomes in crescentic IgA nephropathy in a multicenter cohort study. J Am Soc Nephrol. 2013 Dec;24(12):2118-25. doi: 10.1681/ASN.2012101017. Epub 2013 Sep 12. — View Citation

Nicholls K, Becker G, Walker R, Wright C, Kincaid-Smith P. Plasma exchange in progressive IgA nephropathy. J Clin Apher. 1990;5(3):128-32. — View Citation

Nicholls K, Walker RG, Dowling JP, Kincaid-Smith P. "Malignant" IgA nephropathy. Am J Kidney Dis. 1985 Jan;5(1):42-6. — View Citation

Pankhurst T, Lepenies J, Nightingale P, Howie AJ, Adu D, Harper L. Vasculitic IgA nephropathy: prognosis and outcome. Nephron Clin Pract. 2009;112(1):c16-24. doi: 10.1159/000210570. Epub 2009 Apr 3. — View Citation

Roccatello D, Ferro M, Coppo R, Giraudo G, Quattrocchio G, Piccoli G. Report on intensive treatment of extracapillary glomerulonephritis with focus on crescentic IgA nephropathy. Nephrol Dial Transplant. 1995 Nov;10(11):2054-9. — View Citation

Schwartz J, Winters JL, Padmanabhan A, Balogun RA, Delaney M, Linenberger ML, Szczepiorkowski ZM, Williams ME, Wu Y, Shaz BH. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: the sixth special issue. J Clin Apher. 2013 Jul;28(3):145-284. doi: 10.1002/jca.21276. — View Citation

Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, Wyatt RJ, Scolari F, Mestecky J, Gharavi AG, Julian BA. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011 Oct;22(10):1795-803. doi: 10.1681/ASN.2011050464. Epub 2011 Sep 23. Review. — View Citation

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. — View Citation

Tumlin JA, Lohavichan V, Hennigar R. Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide. Nephrol Dial Transplant. 2003 Jul;18(7):1321-9. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rate of serious adverse events	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	From 12 months after first subject enrolled to 12 months after final subject is enrolled
Primary	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	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
Secondary	Proteinuria remission	Proteinuria remission: defined as proteinuria < 0.5g/d for =3months	At the 12th month and 36th month after randomization

External Links

•   KDIGO Clinical Practice Guideline for Glomerulonephritis (GN)