Trial of Plasma Exchange for Severe Crescentic IgA Nephropathy (RESCUE)

September 30, 2021 updated by: Hong Zhang, Peking University First Hospital

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100034
        • Renal Division, Department of Medicine, Peking University First Hospital
      • Beijing, Beijing, China, 100034
        • Renal Division, Peking University First Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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:
  • Plasmapheresis
Drug: Methylprednisolone pulse
methylprednisolone 7-15mg/kg/d 3 times, Qd. or Qod
Other Names:
  • Intensive Immunosuppressive treatment
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:
  • Intensive Immunosuppressive treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
End-stage renal disease or death
Time Frame: 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.
12 months after final subject is enrolled

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Renal remission
Time Frame: 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
12 months after final subject is enrolled
Proteinuria remission
Time Frame: At the 12th month and 36th month after randomization
Proteinuria remission: defined as proteinuria < 0.5g/d for ≥3months
At the 12th month and 36th month after randomization

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of serious adverse events
Time Frame: 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
From 12 months after first subject enrolled to 12 months after final subject is enrolled

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2016

Primary Completion (Actual)

October 1, 2020

Study Completion (Actual)

October 1, 2020

Study Registration Dates

First Submitted

December 21, 2015

First Submitted That Met QC Criteria

January 4, 2016

First Posted (Estimate)

January 6, 2016

Study Record Updates

Last Update Posted (Actual)

October 8, 2021

Last Update Submitted That Met QC Criteria

September 30, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RESCUE

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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