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

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ClinicalTrials.gov Identifier: NCT02647255
Recruitment Status : Enrolling by invitation
First Posted : January 6, 2016
Last Update Posted : August 29, 2018
Sponsor:
Information provided by (Responsible Party):
Hong Zhang, 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.

Condition or disease Intervention/treatment Phase
Glomerulonephritis, IGA Kidney Diseases Acute Renal Insufficiency Rapidly Progressive Glomerulonephritis Procedure: Plasma Exchange (PE) Drug: Methylprednisolone pulse 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Trial of Plasma Exchange as Adjunctive Therapy for Severe Crescentic GlomerUlonephritis of IgA NEphropathy (RESCUE Study)
Actual Study Start Date : March 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020


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 Name: Plasmapheresis

Drug: Methylprednisolone pulse
methylprednisolone 7-15mg/kg/d 3 times, Qd. or Qod
Other Name: 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 Name: Intensive Immunosuppressive treatment




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. Proteinuria remission [ Time Frame: At the 12th month and 36th month after randomization ]
    Proteinuria remission: defined as proteinuria < 0.5g/d for ≥3months


Other Outcome Measures:
  1. 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




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Ages Eligible for Study:   14 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02647255


Locations
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China, Beijing
Renal Division, Department of Medicine, Peking University First Hospital
Beijing, Beijing, China, 100034
Renal division, Peking University First Hospital
Beijing, Beijing, China, 100034
Sponsors and Collaborators
Peking University First Hospital
Investigators
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Study Director: Hong Zhang, MD, PHD Renal Division, Department of Medicine, Peking University First Hospital;Peking University Institute of Nephrology

Additional Information:
Publications:

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Responsible Party: Hong Zhang, Professor, Principal Investigator, Peking University First Hospital
ClinicalTrials.gov Identifier: NCT02647255     History of Changes
Other Study ID Numbers: RESCUE
First Posted: January 6, 2016    Key Record Dates
Last Update Posted: August 29, 2018
Last Verified: August 2018
Keywords provided by Hong Zhang, Peking University First Hospital:
crescentic IgA nephropathy
plasma exchange treatment or plasmapheresis
randomized controlled trial
intensive immunosuppressive treatment
methylprednisolone pulse
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency
Glomerulonephritis, IGA
Glomerulonephritis
Acute Kidney Injury
Urologic Diseases
Nephritis
Autoimmune Diseases
Immune System Diseases
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents