Minimizing Glucocorticoid Administration in Patients With Proliferative Lupus Nephritis

Phase 4RecruitingNCT05207358

Institutul Clinic Fundeni30 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Lupus Nephritis

Interventions

RituximabDRUG

2 doses of Rituximab 1 g and Methylprednisolone 500 mg on days 1 and 15.

Mycophenolate MofetilDRUG

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.

CyclophosphamideDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (1)

Fundeni Clinical Institute

Bucharest, Romania

RECRUITING

Outcomes

Primary Outcomes

Percentage of participants with a histological remission

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.

Time frame: 6 months

Secondary Outcomes

Percentage of participants with a complete renal response

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.

Time frame: 12 months

Percentage of patients with severe infectious episodes effects

Time frame: 24 months

Cumulative exposure to glucocorticoids

Time frame: 24 months

The proportion of patients who obtained a complete renal response

Time frame: 6, 18 and 24 months

The proportion of patients who obtained a partial renal response

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.

Time frame: 6, 12, 18, 24 months

The proportion of patients who have developed relapse

Time frame: 24 months

Proportion of patients who showed normalization of complement fractions C3, C4 and negative anti-dcDNA antibodies at week 52

Central Contacts

Bogdan Obrisca, MD, PhD

CONTACT

0040721256797 obriscabogdan@yahoo.com

Alexandra Vornicu, MD

CONTACT

0040756203773 vornicu.alexandra@yahoo.com

Data from ClinicalTrials.gov

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