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Per-protocol Repeat Kidney Biopsy in Incident Cases of Lupus Nephritis (REBIOLUP)

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ClinicalTrials.gov Identifier: NCT04449991
Recruitment Status : Not yet recruiting
First Posted : June 29, 2020
Last Update Posted : April 1, 2021
Sponsor:
Collaborator:
Université Catholique de Louvain
Information provided by (Responsible Party):
Ioannis Parodis, Karolinska Institutet

Brief Summary:

Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Among people living with SLE, 35-60% will develop LN during the course of the disease. This complication is one of the factors that contribute to deterioration of the renal function.

Some centres perform kidney biopsies after completion of treatment for an episode of LN as a part of the treatment evaluation. The term "repeat biopsy" is often used to describe these biopsies. Several studies have reported that repeat kidney biopsies show activity at the level of tissue, even in patients with normal routine blood and urine markers. The investigators strongly believe that this information is important, and should be taken into consideration during decision of treatment. To provide evidence for this, the investigators have designed a collaborative project within the frame of the Lupus Nephritis Trials Network. With this research project, the investigators want to contribute to an increased proportion of patients with LN who achieve remission (inactivity) of LN, and a reduced proportion of patients who worsen in renal function in the long term.

Patients with SLE who develop a first episode of LN will be asked to participate in this project, and will receive treatment according to current guidelines. Half of the patients will undergo a repeat biopsy 12 months later, and half of the patients will not. The selection of patients who will undergo or not undergo repeat biopsy will be random. Patients with high disease activity at the level of kidney tissue will receive more intense immunosuppressive treatment. Patients who have not undergone repeat biopsy will continue to be treated according to standard routine.

The investigators will compare the results of treatment between the group of patients who underwent and the group of patients who did not undergo repeat biopsy, with regard to (i) complete disease inactivity at month 24 and (ii) renal function at month 60 from treatment initiation.

The investigators expect that significantly greater proportions of patients in the repeat biopsy group will have inactive disease at month 24 and adequate levels of renal function at month 60. This will provide support for performing repeat biopsies as a part of the treatment evaluation, in order to optimise the therapeutic management and improve the long-term prognosis of patients with LN.


Condition or disease Intervention/treatment Phase
Lupus Nephritis Procedure: Repeat kidney biopsy Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 206 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: At baseline, patients will be randomised 1:1 to either undergo or not undergo a per-protocol repeat kidney biopsy at month 12 from baseline.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Per-protocol Repeat Kidney Biopsy in Incident Cases of Lupus Nephritis
Estimated Study Start Date : June 2021
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy

Arm Intervention/treatment
Experimental: Intervention arm: Repeat kidney biopsy at M12
Patients will undergo repeat kidney biopsy at month 12 from baseline.
Procedure: Repeat kidney biopsy
Intensification of immunosuppression if NIH AI > 3

No Intervention: Control arm: No repeat kidney biopsy
Patients will not undergo repeat kidney biopsy at month 12 from baseline.



Primary Outcome Measures :
  1. Complete Renal Response (CRR) at month 24 from baseline [ Time Frame: Month 24 from baseline ]
    UPCR ≤ 0.5 g/g in two consecutive first-morning void urine specimens and no increase in serum creatinine by ≥ 25% from baseline.


Secondary Outcome Measures :
  1. Renal function impairment at month 60 [ Time Frame: Month 60 from baseline ]
    Sustained (i.e. observed in at least two consecutive measurements on different dates) increase in serum creatinine by ≥ 25% from baseline.

  2. Renal relapse (proteinuric flare) [ Time Frame: Between month 12 and month 60 from baseline ]
    Reappearance of UPCR > 1.0 g/g from month 12 onwards, leading to intensification or change of immunosuppressive therapy. This increased proteinuria has to be sustained (i.e. observed in at least two consecutive measurements on different dates), occurring after an initial response to induction therapy (defined as sustained UPCR < 0.5 g/g).

  3. Reabsorption of immune deposits in repeat kidney biopsies [ Time Frame: Month 12 from baseline ]
    ≥ 50% decrease in intensity and amount of immune deposits in electron microscopy.

  4. End-stage kidney disease (ESKD) [ Time Frame: Between month 12 and month 60 from baseline ]
    Chronic kidney disease stage 5 and/or dialysis will be used to assess ESKD.

  5. Mortality rate [ Time Frame: Between month 12 and month 60 from baseline ]
    The number of deaths during the study period.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Fulfilment of the EULAR/ACR classification criteria of SLE.
  • 18 years of age or above.
  • Incident biopsy-proven proliferative or membranous LN, or combinations thereof (with UPCR ≥ 1 g/g), i.e. 2003 ISN/RPS class III (A or A/C) ± V, class IV (A or A/C) ± V, or class V.
  • Consent to the possibility of a repeat kidney biopsy at month 12 from baseline.
  • Initiation of the following treatment regimens:

    • intravenous pulses of methylprednisolone (total dose of 500-3000 mg);
    • oral prednisone or equivalent 0.3-0.5 mg/kg/day with tapering;
    • hydroxychloroquine unless contraindicated;
    • angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs);
    • either one of mycophenolate mofetil (MMF) equivalent dose 2-3 g/day, or IV cyclophosphamide (CYC) according to the Euro-Lupus regimen;
    • the NIH protocol for IV CYC (0.5-0.75 g/m2 monthly for six months) could be considered in severe cases;
    • add-on therapies (e.g. calcineurin inhibitors, biologics) to the above two regimens are optional.

Exclusion Criteria:

  • Antiphospholipid syndrome nephropathy (APSN).
  • Pregnancy at baseline (pregnancy during follow-up will not lead to exclusion).
  • Medical contraindications to kidney biopsy, e.g. thrombocytopenia < 50,000/μL, uncontrolled hypertension or end-stage kidney disease (ESKD).
  • Anticipated non-adherence to therapy.
  • Medical conditions interfering with outcome evaluations.
  • Inability to read and/or sign the informed consent form.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04449991


Contacts
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Contact: Ioannis Parodis, MD PhD +46722321322 ioannis.parodis@ki.se
Contact: Farah Tamirou, MD PhD +32487586016 farah.tamirou@uclouvain.be

Sponsors and Collaborators
Karolinska Institutet
Université Catholique de Louvain
Investigators
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Study Chair: Ioannis Parodis, MD PhD Karolinska Institutet
Study Chair: Farah Tamirou, MD PhD Université Catholique de Louvain
Study Chair: Julia Weinmann-Menke, MD PhD Johannes Gutenberg University Mainz
Study Chair: Hans-Joachim Anders, Professor Ludwig-Maximilians - University of Munich
Study Chair: Brad H Rovin, Professor Ohio State University
Study Chair: Frédéric A Houssiau, Professor Université Catholique de Louvain
Publications:
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Responsible Party: Ioannis Parodis, Principle Investigator, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT04449991    
Other Study ID Numbers: REBIOLUP
First Posted: June 29, 2020    Key Record Dates
Last Update Posted: April 1, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Datasets needed for addressing research questions that have not been addressed in the original publications.
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: Starting ten years after the baseline visit of the last study participant recruited.
Access Criteria: The REBIOLUP steering committee will review all proposals and provide IPD to investigators upon reasonable request, however highly depending on the research questions to be addressed.
URL: http://rebiolup.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ioannis Parodis, Karolinska Institutet:
systemic lupus erythematosus
lupus nephritis
kidney biopsy
renal function impairment
long-term prognosis
electron microscopy
Additional relevant MeSH terms:
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Nephritis
Lupus Nephritis
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases