Lupus Nephritis
Conditions
Keywords
immunosuppression, glucocorticoids, eurolupus, rituxilup, induction therapy
Brief summary
The aim of the study is to evaluate the efficacy of a therapeutic regimen which decreases glucocorticoid exposure compared with standard therapy in patients with proliferative lupus nephritis during remission induction by evaluating the histological and clinical remission.
Detailed description
After an initial screening phase during which a first kidney biopsy is performed, all patients that meet the inclusion criteria will be randomized to one of the treatment arms: * EUROLUPUS regimen: 3 daily pulses of 750 mg of intravenous Methylprednisolone, followed by oral corticosteroid therapy starting with a dose of 0.5 mg / kg / day for 4 weeks, then decreased by 2.5 mg of Prednisolone / day each 2 weeks. A low dose of glucocorticoid (5-7.5 mg / day) is maintained until 24 months after enrollment. All patients will receive Cyclophosphamide intravenously starting day 1, 6 pulses at a fixed dose of 500 mg given at 2 weeks. After 3 months, Azathioprine (2 mg / kg / day) is initiated 2 weeks after the last administration of Cyclophosphamide and maintained for the next 21 months. * RITUXILUP regimen: 2 doses of Rituximab 1 g and Methylprednisolone 500 mg on days 1 and 15. Patients will receive Mycophenolate Mofetil, initially 500 mg twice daily, titrated to a maximum of 1.5 g twice daily, depending on leukocyte count and digestive tolerance, which will be maintained 24 months. Second kidney biopsy will be performed 6 months after the start of the treatment phase.
Interventions
DRUGRituximab
2 doses of Rituximab 1 g and Methylprednisolone 500 mg on days 1 and 15.
DRUGMycophenolate Mofetil
Patients will receive Mycophenolate Mofetil, initially 500 mg twice daily, titrated to a maximum of 1.5 g twice daily, depending on leukocyte count and digestive tolerance, which will be maintained 24 months.
DRUGCyclophosphamide
All patients will receive Cyclophosphamide intravenously starting day 1, 6 pulses at a fixed dose of 500 mg given at 2 weeks. After 3 months, Azathioprine (2 mg / kg / day) is initiated 2 weeks after the last administration of Cyclophosphamide and maintained for the next 21 months.
DRUGCorticosteroids
3 daily pulses of 750 mg of intravenous Methylprednisolone, followed by oral corticosteroid therapy starting with a dose of 0.5 mg / kg / day for 4 weeks, then decreased by 2.5 mg of Prednisolone / day each 2 weeks. A low dose of glucocorticoid (5-7.5 mg / day) is maintained until 24 months after enrollment.
Sponsors
Institutul Clinic Fundeni
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age of the patient between 18 and 80 years, * Patients diagnosed with systemic lupus erythematosus according to ACR 1997 or SLICC-2012 criteria * Diagnosis of proliferative lupus nephritis class III, IV +/- V (confirmed by renal biopsy and classified according to ISN / RPS); * Estimated glomerular filtration rate by CKD-EPI\> 30 ml / min / 1.73 sqm * Estimated glomerular filtration rate by CKD-EPI \<30 ml / min / 1.73 sqm but\> 15 ml / min / 1.73 sqm with chronicity index (according to NIH score) \<6 * Absence of contraindications to the use of Methylprednisolone, Mycophenolate mofetil, oral corticosteroids or Rituximab * Ability to provide informed consent
Exclusion criteria
* The patient's age under 18 years * Patients with life-threatening complications (e.g. Cerebritis) * Estimated glomerular filtration rate by CKD-EPI \<30 ml / min / 1.73 sqm * Estimated glomerular filtration rate by CKD-EPI \<30 ml / min / 1.73 sqm but\> 15 ml / min / 1.73 sqm with chronicity index (according to NIH score)\> 6 * Presence of pregnancy / lactation * Patients who have received more than 2 g of Methylprednisolone intravenously in the last 4 weeks * Use in the last 3 months of biological therapy * Use of intravenous immunoglobulins / plasmapheresis in the last 6 months * The presence of an active infection * History of neoplasia * Comorbidities requiring systemic corticosteroid therapy * Non-adhesion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with a histological remission | 6 months | The primary endpoint is to evaluate the histologic remission at 6 months after initiation of induction treatment assessed by the change in the individual active lesions and in the activity modified NIH score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients with severe infectious episodes effects | 24 months | — |
| Cumulative exposure to glucocorticoids | 24 months | — |
| The proportion of patients who obtained a complete renal response | 6, 18 and 24 months | — |
| The proportion of patients who obtained a partial renal response | 6, 12, 18, 24 months | Partial renal response is defined as a 50% decrease in proteinuria (if the proteinuria was nephrotic the decrease is defined as a 50% reduction in proteinuria to values \<3000 mg / g) and stabilization (+/- 25%) or decrease, but not normalization of serum Creatinine. |
| The proportion of patients who have developed relapse | 24 months | — |
| Percentage of participants with a complete renal response | 12 months | Complete renal response is defined by the combination of a decrease in proteinuria below 500 mg / g Creatinine, an inactive urinary sediment and a return of serum Creatinine to baseline. |
| Proportion of patients with progression of chronicity score by more than 2 units | 6 months | Evaluation of the histologic progression at 6 months after initiation of induction treatment assessed by the change in the individual chronic lesions and in the chronicity modified NIH score. |
| Percentage of patients with non-severe infectious episodes | 24 months | — |
| Percentage of patients with severe non-infectious adverse events | 24 months | — |
| Percentage of patients with non-severe non-infectious adverse events | 24 months | — |
| Proportion of patients who showed normalization of complement fractions C3, C4 and negative anti-dcDNA antibodies at week 52 | 52 weeks | — |
Countries
Romania
Contacts
Primary ContactBogdan Obrisca, MD, PhD
Backup ContactAlexandra Vornicu, MD
Outcome results
None listed