Clinical Trial: Immunoadsorption in Anti-GBM Glomerulonephritis.
Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional
Official Title: Immunoadsorption in Anti-glomerular Basement Membrane Glomerulonephritis; a Pilot Study
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 Summary:
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 tre
Sponsor: University Medical Center Groningen
Current Primary Outcome: Number of days that anti-GBM antibody titre is above a toxic level, defined as >30 ELISA units. [ Time Frame: 60 days after study start ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 60 days after study start ]
- Logistic feasibility defined as the time interval between diagnosis and start of first immunoadsorption treatment. [ Time Frame: 60 days ]
- Costs of immunoadsorption (personnel and materials). [ Time Frame: 60 days ]
Original Secondary Outcome: Same as current
Information By: University Medical Center Groningen
Dates:
Date Received: May 3, 2016
Date Started: June 2016
Date Completion: December 2018
Last Updated: May 6, 2016
Last Verified: May 2016
