Minimizing Glucocorticoid Administration in Patients With Proliferative Lupus Nephritis (GLUREDLUP)

Institutul Clinic Fundeni

Status and phase: Enrolling; Phase 4

Conditions: Lupus Nephritis

Treatments: Drug: Rituximab; Drug: Cyclophosphamide; Drug: Mycophenolate Mofetil; Drug: Corticosteroids

Study type: Interventional

Funder types: Other

Identifiers

NCT05207358

FundeniCI

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

30 participants in 2 patient groups

RITUXILUP regimen

Experimental group

Description:

- 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.

Treatment:

Drug: Mycophenolate Mofetil

Drug: Rituximab

EUROLUPUS regimen (Standard therapy)

Other group

Description:

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.

Treatment:

Drug: Cyclophosphamide

Drug: Corticosteroids