Trial of Plasma Exchange for Severe Crescentic IgA Nephropathy

NCT02647255 | Terminated Phase 2 DMC

• 1 other identifier: RESCUE
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

crescentic IgA nephropathy; plasma exchange treatment or plasmapheresis; randomized controlled trial; intensive immunosuppressive treatment; methylprednisolone pulse

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Renal remission

  12 months after final subject is enrolled

• Proteinuria remission

  At the 12th month and 36th month after randomization

Other Outcomes (1)

• Rate of serious adverse events

  From 12 months after first subject enrolled to 12 months after final subject is enrolled

Study Arms (2)

PE and methylprednisolone pulse

EXPERIMENTAL

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); Drug: Methylprednisolone pulse

Methylprednisolone pulse

ACTIVE COMPARATOR

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

Interventions

Plasma Exchange (PE) PROCEDURE

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)

Also known as: Plasmapheresis

PE and methylprednisolone pulse

Methylprednisolone pulse DRUG

methylprednisolone 7-15mg/kg/d 3 times, Qd. or Qod

Also known as: Intensive Immunosuppressive treatment

Methylprednisolone pulse; PE and methylprednisolone pulse

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \<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.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (2)

Renal Division, Department of Medicine, Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Renal division, Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Related Publications (14)

• 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.

  PMID: 21949093 BACKGROUND

• 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.

  PMID: 24029421 BACKGROUND

• 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.

  PMID: 3955907 BACKGROUND

• 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. doi: 10.1159/000065281.

  PMID: 12381947 BACKGROUND

• 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. doi: 10.1093/ndt/gfg081.

  PMID: 12808169 BACKGROUND

• 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.

  PMID: 19342865 BACKGROUND

• 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. doi: 10.1681/ASN.2007010090. Epub 2007 Jun 20.

  PMID: 17582159 BACKGROUND

• 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. doi: 10.1002/jca.2920050303.

  PMID: 2345159 BACKGROUND

• 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. doi: 10.1016/s0272-6386(87)80014-8.

  PMID: 3300287 BACKGROUND

• 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. doi: 10.1007/s00467-006-0428-4. Epub 2007 Feb 7.

  PMID: 17285293 BACKGROUND

• Nicholls K, Walker RG, Dowling JP, Kincaid-Smith P. "Malignant" IgA nephropathy. Am J Kidney Dis. 1985 Jan;5(1):42-6. doi: 10.1016/s0272-6386(85)80134-7.

  PMID: 3966468 BACKGROUND

• 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.

  PMID: 8643167 BACKGROUND

• 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.

  PMID: 23868759 BACKGROUND

• Tunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.pub3.

  PMID: 38299639 DERIVED

Related Links

• KDIGO Clinical Practice Guideline for Glomerulonephritis (GN)

MeSH Terms

Conditions

Glomerulonephritis, IGA; Kidney Diseases; Acute Kidney Injury

Interventions

Plasma Exchange; Plasmapheresis

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases; Renal Insufficiency

Intervention Hierarchy (Ancestors)

Blood Transfusion; Biological Therapy; Therapeutics; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Hong Zhang, MD, PHD

  Renal Division, Department of Medicine, Peking University First Hospital;Peking University Institute of Nephrology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Principal Investigator

Study Record Dates

• First Submitted: December 21, 2015
• First Posted: January 6, 2016
• Study Start: March 1, 2016
• Primary Completion: October 1, 2020
• Study Completion: October 1, 2020
• Last Updated: October 8, 2021

Record last verified: 2021-09

Locations

CN (2)