Immunoadsorption in Anti-GBM Glomerulonephritis.
Primary Purpose
Anti-glomerular Basement Membrane Glomerulonephritis
Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Immunoadsorption (Immunosorba)
Sponsored by
About this trial
This is an interventional treatment trial for Anti-glomerular Basement Membrane Glomerulonephritis
Eligibility Criteria
Inclusion Criteria:
Acute renal failure due to anti-GBM glomerulonephritis with or without pulmonary involvement. Eligible patients must have a clinical picture met rapidly progressive glomerulonephritis in combination with one of the following:
- Serological evidence of circulating anti-GMB antibodies (Dotblot, Phadia, ELISA). Patients with dual autoantibody positivity (anti-GBM antibodies and ANCA) can participate in this study. 2. Renal biopsy with necrotising glomerulonephritis with linear fluorescence for IgG along the GBM.
Exclusion Criteria:
- Pregnancy
Sites / Locations
- University Medical Center Groningen
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Immunoadsorption
Arm Description
Immunoadsoprtion (Immunosorba). All (anticipated) 8 participants will be treated with immunoadsorption
Outcomes
Primary Outcome Measures
Number of days that anti-GBM antibody titre is above a toxic level, defined as >30 ELISA units.
Nr of Days that anti-GBM title is >30 units
Secondary Outcome Measures
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
NR of participants with adverse event
Logistic feasibility defined as the time interval between diagnosis and start of first immunoadsorption treatment.
Time interval between diagnosis and start of first immunoadsorption treatment
Costs of immunoadsorption (personnel and materials).
Costs of immunoadsorption treatment
Full Information
NCT ID
NCT02765789
First Posted
May 3, 2016
Last Updated
November 6, 2022
Sponsor
University Medical Center Groningen
Collaborators
Fresenius Medical Care North America
1. Study Identification
Unique Protocol Identification Number
NCT02765789
Brief Title
Immunoadsorption in Anti-GBM Glomerulonephritis.
Official Title
Immunoadsorption in Anti-glomerular Basement Membrane Glomerulonephritis; a Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
June 1, 2016 (Actual)
Primary Completion Date
July 7, 2021 (Actual)
Study Completion Date
July 7, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen
Collaborators
Fresenius Medical Care North America
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Anti-glomerular basement membrane (GBM) glomerulonephritis is a rare autoimmune disease mediated by anti-GBM antibodies and characterized by acute renal failure due to diffuse crescentic glomerulonephritis. Established treatment is cyclophosphamide and corticosteroids to suppress anti-GBM production and daily plasma exchange to remove circulating anti-GBM antibodies. The vast majority of patients with anti-GBM glomerulonephritis develop irreversible end-stage renal failure despite this treatment. Immunoadsorption may lower anti-GBM titres more effectively than plasma exchange. The goal of this interventional open, non-randomized pilot study is to study the efficacy, adverse events, logistic feasibility and costs of immuno-adsorption for the removal of anti-GBM antibodies in patients with acute renal failure due to anti-GBM glomerulonephritis. Eight patients with acute renal failure due to anti-GBM glomerulonephritis with or without accompanying pulmonary involvement will be treated with daily immunoadsorption, instead of plasma exchange, until anti-GBM titres are undetectable. All other aspects of the treatment (e.g. immunosuppressive treatment, renal replacement therapy) will be standard. The primary study parameter is the number of days that anti-GBM antibody titre is above a toxic level, defined as >30 ELISA units. Secondary study parameters are the tolerability and adverse events of immunoadsorption, the logistic feasibility defined as the time interval between diagnosis and start of first immunoadsorption treatment and costs of immunoadsorption.
Detailed Description
Rationale: Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is a rare organ-specific autoimmune disease that is mediated by anti-GBM antibodies. It is characterized by acute renal failure due to diffuse crescentic glomerulonephritis, often accompanied by pulmonary hemorrhage. Established treatment is cyclophosphamide and corticosteroids to suppress anti-GBM production and daily plasma exchange to remove circulating anti-GBM antibodies. The vast majority of patients with anti-GBM glomerulonephritis develop irreversible end-stage renal failure despite this treatment. The treatment goal in anti-GBM glomerulonephritis is to achieve undetectable anti-GBM titres as rapid as possible. Immunoadsorption is an extracorporeal technique that selectively removes antibodies and may lower anti-GBM titres more effectively than plasma exchange. With this technique the patient's plasma is passed through an immunoadsorption column that contains protein A that binds antibodies of the IgG class like anti-GBM antibodies. However, data on the efficacy of anti-GBM removal by immunoadsorption compared with plasma exchange are scarce. In the literature, there are only a few case descriptions of the clinical effect of immunoadsorption in patients with anti-GBM disease with some cases showing recovery of renal function despite unfavourable prognosis (serum creatinine >500 µmol/l and/or high percentage of crescents on renal biopsy). Immunoadsorption is presently not used in the Netherlands for anti-GBM disease.
Objective: To study the efficacy, adverse events, logistic feasibility and costs of immuno-adsorption for the removal of anti-GBM antibodies in patients with acute renal failure due to anti-GBM glomerulonephritis.
Study design: Interventional, open, non-randomized, pilot study. After informed consent, patients will be treated according to the current treatment protocol with the exception of daily immunoadsorption instead of daily plasma exchange.
Study population: 8 patients with acute renal failure due to anti-GBM glomerulonephritis with or without accompanying pulmonary involvement.
Intervention: Participating patients will be treated with daily immunoadsorption (2.5 times the plasma volume), instead of plasma exchange, until anti-GBM titres are undetectable. All other aspects of the treatment (e.g. immunosuppressive treatment, renal replacement therapy) will be standard.
Main study parameters/endpoints: The primary study parameter is the number of days that anti-GBM antibody titre is above a toxic level, defined as >30 ELISA units. Plasma levels of anti-GBM will be measured before and after each immunoadsorption treatment. Courses of anti-GBM titres will be compared with an historical cohort of patients with anti-GBM disease treated with plasma exchange. Secondary study parameters are: 1. Tolerability and adverse events of immunoadsorption. 2. Logistic feasibility defined as the time interval between diagnosis and start of first immunoadsorption treatment; 3. Costs of immunoadsorption (personnel and materials).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: From a patient's perspective, the burden of daily immunoadsorption is comparable with that of daily plasma exchange with regard to vascular access (central venous catheter) and blood sampling to monitor treatment response. The treatment time is approximately one hour longer than plasma exchange (4 hours instead of 3 hours). Possible adverse effects of immunoadsorption are part of the current study proposal but previous studies in other patient groups suggest that frequency and severity of adverse effects of immunoadsorption are comparable with plasma exchange.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anti-glomerular Basement Membrane Glomerulonephritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Immunoadsorption
Arm Type
Experimental
Arm Description
Immunoadsoprtion (Immunosorba). All (anticipated) 8 participants will be treated with immunoadsorption
Intervention Type
Device
Intervention Name(s)
Immunoadsorption (Immunosorba)
Intervention Description
Immunoadsorption as an alternative to plasma exchange
Primary Outcome Measure Information:
Title
Number of days that anti-GBM antibody titre is above a toxic level, defined as >30 ELISA units.
Description
Nr of Days that anti-GBM title is >30 units
Time Frame
60 days after study start
Secondary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
NR of participants with adverse event
Time Frame
60 days after study start
Title
Logistic feasibility defined as the time interval between diagnosis and start of first immunoadsorption treatment.
Description
Time interval between diagnosis and start of first immunoadsorption treatment
Time Frame
60 days
Title
Costs of immunoadsorption (personnel and materials).
Description
Costs of immunoadsorption treatment
Time Frame
60 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Acute renal failure due to anti-GBM glomerulonephritis with or without pulmonary involvement. Eligible patients must have a clinical picture met rapidly progressive glomerulonephritis in combination with one of the following:
Serological evidence of circulating anti-GMB antibodies (Dotblot, Phadia, ELISA). Patients with dual autoantibody positivity (anti-GBM antibodies and ANCA) can participate in this study. 2. Renal biopsy with necrotising glomerulonephritis with linear fluorescence for IgG along the GBM.
Exclusion Criteria:
Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Casper FM Franssen, MD PhD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Center Groningen
City
Groningen
State/Province
Gromiongen
ZIP/Postal Code
9713 GZ
Country
Netherlands
12. IPD Sharing Statement
Plan to Share IPD
No
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Immunoadsorption in Anti-GBM Glomerulonephritis.
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