Clinical trial NCT05207358: Minimizing Glucocorticoid Administration in Patients With Proliferative Lupus Nephritis
Official title: Minimizing Glucocorticoid Administration in Patients With Proliferative Lupus Nephritis During the Induction of Remission Period-EUROLUPUS vs. RITUXILUP Regimen: A Randomized Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Lupus Nephritis
Keywords: immunosuppression
glucocorticoids
eurolupus
rituxilup
induction therapy
Lead sponsor: Institutul Clinic Fundeni
Sponsor class: OTHER
First posted: 2022-01-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of participants with a histological remission
timeFrame: 6 months
Secondary outcomes:
measure: Percentage of participants with a complete renal response
timeFrame: 12 months
measure: Percentage of patients with severe infectious episodes effects
timeFrame: 24 months
measure: Cumulative exposure to glucocorticoids
timeFrame: 24 months
measure: The proportion of patients who obtained a complete renal response
timeFrame: 6, 18 and 24 months
measure: The proportion of patients who obtained a partial renal response
timeFrame: 6, 12, 18, 24 months
measure: The proportion of patients who have developed relapse
timeFrame: 24 months
measure: Proportion of patients who showed normalization of complement fractions C3, C4 and negative anti-dcDNA antibodies at week 52
timeFrame: 52 weeks
measure: Proportion of patients with progression of chronicity score by more than 2 units
timeFrame: 6 months
measure: Percentage of patients with non-severe infectious episodes
timeFrame: 24 months
measure: Percentage of patients with severe non-infectious adverse events
timeFrame: 24 months
measure: Percentage of patients with non-severe non-infectious adverse events
timeFrame: 24 months
Other outcomes:
Locations:
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute
Study officials:
affiliation: Institutul Clinic Fundeni
name: Gener Ismail, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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