Minimizing Glucocorticoid Administration in Patients With Proliferative Lupus Nephritis

NCT ID: NCT05207358

Last Updated: 2022-03-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-02

Study Completion Date

2028-12-31

Brief Summary

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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

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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.

Conditions

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Lupus Nephritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

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

Mycophenolate Mofetil

Intervention Type DRUG

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)

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.

Group Type OTHER

Cyclophosphamide

Intervention Type DRUG

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.

Corticosteroids

Intervention Type DRUG

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.

Interventions

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Rituximab

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

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institutul Clinic Fundeni

OTHER

Sponsor Role lead

Responsible Party

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Bogdan Obrisca

Assist. Prof.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Gener Ismail, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institutul Clinic Fundeni

Locations

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Fundeni Clinical Institute

Bucharest, , Romania

Site Status RECRUITING

Countries

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Romania

Central Contacts

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Bogdan Obrisca, MD, PhD

Role: CONTACT

0040721256797

Alexandra Vornicu, MD

Role: CONTACT

0040756203773

Facility Contacts

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Bogdan Obrisca, MD, PhD

Role: primary

0040721256797

References

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Parikh SV, Almaani S, Brodsky S, Rovin BH. Update on Lupus Nephritis: Core Curriculum 2020. Am J Kidney Dis. 2020 Aug;76(2):265-281. doi: 10.1053/j.ajkd.2019.10.017. Epub 2020 Mar 24.

Reference Type BACKGROUND
PMID: 32220510 (View on PubMed)

Pepper R, Griffith M, Kirwan C, Levy J, Taube D, Pusey C, Lightstone L, Cairns T. Rituximab is an effective treatment for lupus nephritis and allows a reduction in maintenance steroids. Nephrol Dial Transplant. 2009 Dec;24(12):3717-23. doi: 10.1093/ndt/gfp336. Epub 2009 Jul 17.

Reference Type BACKGROUND
PMID: 19617257 (View on PubMed)

Fanouriakis A, Bertsias G. Changing paradigms in the treatment of systemic lupus erythematosus. Lupus Sci Med. 2019 Feb 8;6(1):e000310. doi: 10.1136/lupus-2018-000310. eCollection 2019.

Reference Type BACKGROUND
PMID: 31168398 (View on PubMed)

Parikh SV, Rovin BH. Current and Emerging Therapies for Lupus Nephritis. J Am Soc Nephrol. 2016 Oct;27(10):2929-2939. doi: 10.1681/ASN.2016040415. Epub 2016 Jun 9.

Reference Type BACKGROUND
PMID: 27283496 (View on PubMed)

Catapano F, Chaudhry AN, Jones RB, Smith KG, Jayne DW. Long-term efficacy and safety of rituximab in refractory and relapsing systemic lupus erythematosus. Nephrol Dial Transplant. 2010 Nov;25(11):3586-92. doi: 10.1093/ndt/gfq256. Epub 2010 May 11.

Reference Type BACKGROUND
PMID: 20466686 (View on PubMed)

Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, Appel G; LUNAR Investigator Group. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012 Apr;64(4):1215-26. doi: 10.1002/art.34359. Epub 2012 Jan 9.

Reference Type BACKGROUND
PMID: 22231479 (View on PubMed)

Tamirou F, Houssiau FA. Management of Lupus Nephritis. J Clin Med. 2021 Feb 9;10(4):670. doi: 10.3390/jcm10040670.

Reference Type BACKGROUND
PMID: 33572385 (View on PubMed)

Condon MB, Ashby D, Pepper RJ, Cook HT, Levy JB, Griffith M, Cairns TD, Lightstone L. Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis. 2013 Aug;72(8):1280-6. doi: 10.1136/annrheumdis-2012-202844. Epub 2013 Jun 5.

Reference Type BACKGROUND
PMID: 23740227 (View on PubMed)

Morales E, Galindo M, Trujillo H, Praga M. Update on Lupus Nephritis: Looking for a New Vision. Nephron. 2021;145(1):1-13. doi: 10.1159/000511268. Epub 2020 Nov 4.

Reference Type BACKGROUND
PMID: 33147587 (View on PubMed)

Bajema IM, Wilhelmus S, Alpers CE, Bruijn JA, Colvin RB, Cook HT, D'Agati VD, Ferrario F, Haas M, Jennette JC, Joh K, Nast CC, Noel LH, Rijnink EC, Roberts ISD, Seshan SV, Sethi S, Fogo AB. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int. 2018 Apr;93(4):789-796. doi: 10.1016/j.kint.2017.11.023. Epub 2018 Feb 16.

Reference Type BACKGROUND
PMID: 29459092 (View on PubMed)

Other Identifiers

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FundeniCI

Identifier Type: -

Identifier Source: org_study_id

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