To evalute the efficacy of rituximab in comparison to continued corticosteroid treatment in ipatients with diopathic nephrotic syndrome unresponsive to 8 weeks of high dose prednisolone.
ID
Source
Brief title
Condition
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint: The proportion of patients reaching complete remission (CR)
at 8 weeks
Secondary outcome
1. Proportion of patients with a partial remission at 8 weeks
2. Proportion of patients with a late remission (partial and complete) between
2 and 12 months
3. Time to remission (partial and complete) over 12 months
4. Proportion of patients with a relapse and time to remission over 12 months
5. Proportion of patients treated with additional immunosuppressive therapy
other than assigned treatment with rituximab or prednisolone at 2 and
12 months
6. Difference in quality of life measured by RAND-36 and TNO-AZL Questionnaire
for Adult's Health-Related Quality of Life for people of 16 years
and older (TAAQOL) measured at 0, 2 and 12 months
7. Side effects: Proportion of patients with >= 1 adverse event; Proportion of
patients with >= 1 serious adverse event; Proportion of patients with >= 1
adverse event grade 3 or 4; Proportion of patients with >= 1 infection which
required treatment; Proportion of patients with diabetes defined as
new onset diabetes, initiation of treatment with oral antidiabetic
medication or insuline, addition of another class of oral antidiabetics more
Adverse events will be graded according to the Common Terminology Criteria
for Adverse Events (NCI-CTCAE v4.03)
8. Cost-effectiveness analysis and cost-utility analysis according to the
guidelines provided by Zorginstituut Nederland 2015 with use of the
EuroQol-5D-5L measure of health-related quality of life
9. Difference in creatinine clearance and estimated glomerular filtration rate
10. Proportion of patients with an increase of baseline serum creatinine >= 50%
Background summary
Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are
important causes of idiopathic nephrotic syndrome. As advised by national and
international guidelines, initial treatment consists of high dose prednisolone
until a complete remission is achieved with a maximum of 16 weeks. However,
serious concerns exist about the side effects of this treatment. Specifically
treatment > 8 weeks is associated with serious side effects such as weight
gain, diabetes mellitus, striae, cataract, skin and muscle atrophy, and
psychological disturbances. Unfortunately the likelihood of attaining a
remission decreases if prolonged treatment is needed. Retrospective studies
suggested that Rituximab may be more effective in patients unresponsive to 8
weeks of high dose prednisolone. Treatment with rituximab was associated with a
higher proportion of patients attaining remission of proteinuria and with fewer
side effects. A formal, prospective and randomized trial is needed to determine
the efficacy of rituximab regarding remission of proteinuria, time to
remissions, side effects, quality of life, kidney function and costs.
Study objective
To evalute the efficacy of rituximab in comparison to continued corticosteroid
treatment in ipatients with diopathic nephrotic syndrome unresponsive to 8
weeks of high dose prednisolone.
Study design
This will be an open-label, randomized controlled trial which compares
continued treatment with high dose prednisolone (standard therapy) to treatment
with rituximab in patients with an idiopathic nephrotic syndrome. All patients
will be treated with high dose prednisolone (1 mg/kg/day) for 8 weeks according
to current national and international guideline. Patients can be included in
the trial in case of persistent persistent proteinuria >= 2 g/ 24 hours or a
protein-to-creatinine ratio >= 2 g/10mmol (2 g/g) after 8 weeks of treatment
with high dose prednisolone
Patients either receive 2 doses of Rituximab 375 mg/m2 iv at time 0 and 14 days
with termination of prednisolone or standard therapy which consist of 8
additional weeks of high dose prednisolone treatment. In the Rituximab group,
B-cells will be monitored weekly, and if no complete depletion is achieved,
additional dose(s) of Rituximab will be given at a weekly interval (maximum of
2 additional doses) until complete B cell depletion. Second line treatment is
started in both arms in the case of intractable edema. Expected duration of
follow-up is 12 months, consisting of 9 visits.
Intervention
Trial intervention (study treatment in drug clinical trial):
The arms of treatment will be the following:
First arm: Rituximab 375 mg/m2 at t=0 en t= 2 weeks
B-cells will be monitored, and if no complete depletion is
achieved, additional dose(s) of Rituximab will be given at a weekly interval
until complete B cell depletion (maximum of 2 additional
doses)
Second arm: Standard treatment with prednisolone 1 mg/kg/day (max 80 mg/day)
for 8 weeks
Study burden and risks
For patients in the control arm of the study (continued treatment with high
dose prednisolone) the risks associated with participation are not different
from those associated with standard of care treatment, and mainly consist of
the risk of side effects to therapy. There are no direct benefits for these
patients by participating in the study, since they receive the normal standard
of care treatment. For patients treated with rituximab the risks associated
with participation, are also associated with the risk of side effects. In
general side effects of prolonged treatment with high dose prednisolone are
considered more severe.
The number of visits to the hospital is similar to the number of visits needed
for the standard of care treatment. The extra burden associated with
participation consist of visits to the RadboudUMC instead of a local hospital
and more blood samples are collected during the visits.
An extra burden for patients in the Rituximab arm are 2 hospital admissions for
IV administration of rituximab. On the other hand these patients benefit from
cessation of prednisolone therapy. Another benefit of participating in his
study for patients treated with rituximab may be a higher remission rate and
that they theoretically may experience less (severe) side effects than patients
treated with the standard of care protocol.
.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
Age >= 18 years

Persistent proteinuria >= 2 g/ 24 hours or a protein-to-creatinine ratio >= 2 g/10mmol (2 g/g) after 8 weeks of treatment with high dose prednisone 1 mg/kg/day (max 80 mg/day) 

Idiopathic nephrotic syndrome caused by biopsy proven minimal change disease or focal segmental glomerulosclerosis
Exclusion criteria
• Severe nephrotic syndrome with hypotension
• Previous treatment with immunosuppressive medication other than prednisone
• Treatment with prednisone > 10 weeks in last six months
• Secondary form of FSGS or minimal change disease
• Patients who test positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody 
(anti-HBc).
• Patients infected with HIV or suffering from other active infections
• Patients inoculated with a live vaccine within 4 weeks prior to inclusion
• Pregnancy, breast feeding, women with inadequate contraception
• Malignancy
• Kidney transplantation
• Previous treatment with monoclonal antibodies
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2017-003366-27-NL |
| CCMO | NL63099.091.17 |
| Other | volgt |