Minimizing Glucocorticoid Administration in Patients With Proliferative Lupus Nephritis
- Conditions
- Lupus Nephritis
- Interventions
- Registration Number
- NCT05207358
- Lead Sponsor
- Institutul Clinic Fundeni
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description EUROLUPUS regimen (Standard therapy) Corticosteroids 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 Rituximab - 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. RITUXILUP regimen Mycophenolate Mofetil - 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. EUROLUPUS regimen (Standard therapy) Cyclophosphamide 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Percentage of patients with severe infectious episodes effects 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.
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.
Cumulative exposure to glucocorticoids 24 months The proportion of patients who have developed relapse 24 months Percentage of patients with 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 Percentage of patients with non-severe infectious episodes 24 months 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 non-infectious adverse events 24 months
Trial Locations
- Locations (1)
Fundeni Clinical Institute
🇷🇴Bucharest, Romania