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ID
Source
Brief title
Health condition
primary membranous nephropathy
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Cumulative incidence of remissions (complete- and partial remission), for a duration of at least 6 months.
Complete remission (CR) is defined as a protein-creatinine ratio ≤0.2 g/10 mmol creatinine with stable kidney function, and partial remission (PR) is defined as protein-creatinine ratio <3.0 g/10 mmol creatinine with a reduction of >50 % from baseline and stable kidney function. Achieving remission includes both partial and complete remission)
Secondary outcome
- duration of immunosuppressive treatment
- duration till disappearance of anti-PLA2R antibodies
- relapse rate (Relapse is defined as nephrotic proteinuria and an increase of > 50 % compared with the lowest value during remission)
- number of patients in need of additional therapy
- renal function deterioration ((1) a rise in serum creatinine >50%, or 2) a rise in serum creatinine >25% and an absolute level ≥135 µmol/l)
- End-stage renal disease: eGFR <15 ml/min/1.73m2
- Adverse events
- Amount of remissions five years after the start of the initial treatment, with less than the standard immunosuppressive therapy.
Background summary
In 70 % of patients anti-PLA2R antibodies (aPLA2R) can be identified. Although spontaneous remissions do occur, up to 50 % of patients may need immunosuppressive therapy. The KDIGO guideline recommend initial therapy with a 6-month course of alternating monthly cycles of an alkylating agent and steroids. In the literature different treatment protocols with variable duration of drug therapy are used, however in all studies treatment was not personalized. In previous studies it was shown that disappearance of aPLA2R preceded clinical remission by 2-3 months. We observed that in the majority of patients treated with cyclophosphamide (CP) and mycofenolic acid (MMF) aPLA2R disappeared after 2 months. Since august 2013 we use aPLA2R response to determine treatment duration in the individual patient. We use an antibody guided therapy protocol in patients treated with CP, MMF and tacrolimus. We expect that we will shorten the duration of therapy in many patients.
Study objective
In 70 % of patients anti-PLA2R antibodies (aPLA2R) can be identified. Although spontaneous remissions do occur, up to 50 % of patients may need immunosuppressive therapy. The KDIGO guideline recommend initial therapy with a 6-month course of alternating monthly cycles of an alkylating agent and steroids. In the literature different treatment protocols with variable duration of drug therapy are used, however in all studies treatment was not personalized. In previous studies it was shown that disappearance of aPLA2R preceded clinical remission by 2-3 months. We observed that in the majority of patients treated with cyclophosphamide (CP) and mycofenolic acid (MMF) aPLA2R disappeared after 2 months. We use an antibody guided therapy protocol in patients treated with CP, MMF and tacrolimus. We expect that this will shorten the duration of therapy in many patients.
Study design
24 months
Intervention
Since august 2013 we use aPLA2R response to determine treatment duration in the individual patient. In the case of treatment with CP and MMF (both in combination with steroids), aPLA2R are measured after resp. 8, 16 and 24 weeks with a commercial IFT. If antibodies are negative the CP/MMF is stopped and the steroids are tapered. If the aPLA2R antibodies are still positive after 24 weeks of treatment and no complete remission is achieved further treatment with another agent is recommended. A maximum treatment duration of 6 months after the achievement of a partial remission is prescribed.
In case of tacrolimus (also in combination with prednisone); aPLA2R are measured after 24 weeks. If antibodies are negative the tacrolimus and the steroids are tapered. If the aPLA2R are still positive after 24 weeks of treatment further treatment is recommended and aPLA2R are measured again after 48 weeks. If, after 48 weeks of treatment continuation of treatment is recommended and aPLA2R are measured again after 48 weeks. If, after 48 weeks of treatment aPLA2R are still positive and no complete remission is achieved, further treatment with Rituximab (1000 mg) is recommended and the tacrolimus and the steroids are tapered.
For the cyclophamide group a comparison with a historical control group (treated with cyclophosphamide and steroids for 6-12 months) will be made.
Anne-Els van de Logt
Geert Grooteplein Zuid 8
Nijmegen 6500 HB
The Netherlands
Telefonisch: 0243614761
Anne-Els.vandeLogt@radboudumc.nl
Anne-Els van de Logt
Geert Grooteplein Zuid 8
Nijmegen 6500 HB
The Netherlands
Telefonisch: 0243614761
Anne-Els.vandeLogt@radboudumc.nl
Inclusion criteria
- patients with primary membranous nephropathy
- 18 years or older
- anti-PLA2R antibodies positive
- high risk of disease progression. High risk is defined as patients with a persisting nephritic syndrome (>6 months) despite conservative treatment, an urinary βeta-2-microglobulin (β2m) excretion of >1000 ng/min or deteriorating kidney function, or severe symptoms related to the nephrotic syndrome.
Exclusion criteria
- anti-PLA2R antibodies negative
- participation in another clinical trial
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL5890 |
| NTR-old | NTR6078 |
| Other | commissie CMO Arnhem-Nijmegen. : 2014-1418 |