Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02765789 |
| Other study ID # |
201500361 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2016 |
| Est. completion date |
July 7, 2021 |
Study information
| Verified date |
November 2022 |
| Source |
University Medical Center Groningen |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
