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

March 2, 2022 updated by: Bogdan Obrisca, Institutul Clinic Fundeni

Minimizing Glucocorticoid Administration in Patients With Proliferative Lupus Nephritis During the Induction of Remission Period-EUROLUPUS vs. RITUXILUP Regimen: A Randomized Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Romania
      • Bucharest, Romania, 022328
        • Recruiting
        • Fundeni Clinical Institute
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Rituximab
2 doses of Rituximab 1 g and Methylprednisolone 500 mg on days 1 and 15.
Drug: Mycophenolate 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.
Other: EUROLUPUS regimen (Standard therapy)
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.
Drug: Cyclophosphamide
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.
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of participants with a histological remission
Time Frame: 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.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of participants with a complete renal response
Time Frame: 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.
12 months
Percentage of patients with severe infectious episodes effects
Time Frame: 24 months
24 months
Cumulative exposure to glucocorticoids
Time Frame: 24 months
24 months
The proportion of patients who obtained a complete renal response
Time Frame: 6, 18 and 24 months
6, 18 and 24 months
The proportion of patients who obtained a partial renal response
Time Frame: 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.
6, 12, 18, 24 months
The proportion of patients who have developed relapse
Time Frame: 24 months
24 months
Proportion of patients who showed normalization of complement fractions C3, C4 and negative anti-dcDNA antibodies at week 52
Time Frame: 52 weeks
52 weeks
Proportion of patients with progression of chronicity score by more than 2 units
Time Frame: 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.
6 months
Percentage of patients with non-severe infectious episodes
Time Frame: 24 months
24 months
Percentage of patients with severe non-infectious adverse events
Time Frame: 24 months
24 months
Percentage of patients with non-severe non-infectious adverse events
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institutul Clinic Fundeni

Investigators

  • Principal Investigator: Gener Ismail, MD, PhD, Institutul Clinic Fundeni

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2022

Primary Completion (Anticipated)

December 31, 2028

Study Completion (Anticipated)

December 31, 2028

Study Registration Dates

First Submitted

December 7, 2021

First Submitted That Met QC Criteria

January 13, 2022

First Posted (Actual)

January 26, 2022

Study Record Updates

Last Update Posted (Actual)

March 3, 2022

Last Update Submitted That Met QC Criteria

March 2, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FundeniCI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Time Frame

Within 12 months of publishing the results of the primary endpoints of the study

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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