Effectiveness of Mycophenolate Mofetil Combined With Tacrolimus for Steroid Tapering in Systemic Lupus Erythematosus

NCT ID: NCT05916781

Last Updated: 2024-07-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-01
• Study Completion Date: 2026-07-31

Brief Summary

The goal of this clinical trial is to determine whether mycophenolate mofetil(MMF) combined with tacrolimus(TAC) can maintain remission in patients with lupus nephritis (LN) who have reached treatment targets after steroid tapering. The main question[s] it aims to answer are:

• The efficacy, safety and tolerability of MMF combined with TAC regimen in the treatment of LN patients in the maintenance period.
• The influence of low-dose steroid on carotid intima thickness (CIMT).
• The omics and cell-free RNA (cfRNA) spectral differences related to lupus flare.
• The differences in health economics between steroid tapering and steroid maintenance patients.

Participants will be randomly assigned into 2 groups. In the steroid tapering group, participants will take MMF+TAC treatment without steroid for 1 year, and participants who stop steroid treatment without lupus flare will be randomly assigned to monotherapy with MMF or TAC. In the steroid maintenance group, participants will take MMF+TAC+steroid for 1 year, and participants without lupus flare will stop the use of steroid for 6 months. Participants without lupus flare after the stop of steroid will be randomly assigned to monotherapy with MMF or TAC.

Detailed Description

According to the references, with the maintenance of steroid, 1-year lupus flare rate is 7%. Investigators plan to take a 2-year follow-up for participants, so the proportion of patients without flare in steroid maintenance group should be 86%. As this is a non-inferiority study, investigators hypothesize that in steroid tapering group, the proportion of patients without flare is also 86%. Investigators set α=0.05 (two-sided), 1-β=0.90, non-inferiority value = 15%, the dropout rate = 20%. The sample size of each group should be 110, the 220 in total.

Conditions

Systemic Lupus Erythematosus; Lupus Nephritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

steroid tapering group

0\~6th month: mycophenolate mofetil (1g/d) + tacrolimus (2.0mg/d) + steroid (1 pill/d) 6th\~18th month: mycophenolate mofetil (1g/d) + tacrolimus (2.0mg/d) 18th\~30th month: Participants who stop steroid treatment and do not flare will be randomly assigned to monotherapy with mycophenolate mofetil or tacrolimus

Group Type: EXPERIMENTAL

Mycophenolate Mofetil

Intervention Type: DRUG

Participants in steroid tapering group will take MMF+TAC during the first 18 months. After 18 months, participants without lupus flare will randomly stop MMF or TAC.

Participants in steroid maintenance group will take MMF+TAC during the first 24 months. After 24 months, participants without lupus flare will randomly stop MMF or TAC.

Tacrolimus

Intervention Type: DRUG

Participants in steroid tapering group will take MMF+TAC during the first 18 months. After 18 months, participants without lupus flare will randomly stop MMF or TAC.

Participants in steroid maintenance group will take MMF+TAC during the first 24 months. After 24 months, participants without lupus flare will randomly stop MMF or TAC.

Glucocorticoid

Intervention Type: DRUG

Participants in steroid tapering group will stop taking glucocorticoid after the first 6 months.

Participants in steroid maintenance group will consistently take glucocorticoid for 18 months, and stop the use of glucocorticoid after 18 months if they do not flare.

steroid maintenance group

0\~18th month: mycophenolate mofetil (1g/d) + tacrolimus (2.0mg/d) + steroid (1 pill/d) 18th\~24th month: Participants who do not flare will stop the use of steroid. 24th\~30th month: Participants who do not flare will be randomly assigned to monotherapy with mycophenolate mofetil or tacrolimus

Group Type: ACTIVE_COMPARATOR

Mycophenolate Mofetil

Intervention Type: DRUG

Participants in steroid tapering group will take MMF+TAC during the first 18 months. After 18 months, participants without lupus flare will randomly stop MMF or TAC.

Participants in steroid maintenance group will take MMF+TAC during the first 24 months. After 24 months, participants without lupus flare will randomly stop MMF or TAC.

Tacrolimus

Intervention Type: DRUG

Participants in steroid tapering group will take MMF+TAC during the first 18 months. After 18 months, participants without lupus flare will randomly stop MMF or TAC.

Participants in steroid maintenance group will take MMF+TAC during the first 24 months. After 24 months, participants without lupus flare will randomly stop MMF or TAC.

Glucocorticoid

Intervention Type: DRUG

Participants in steroid tapering group will stop taking glucocorticoid after the first 6 months.

Participants in steroid maintenance group will consistently take glucocorticoid for 18 months, and stop the use of glucocorticoid after 18 months if they do not flare.

Interventions

Mycophenolate Mofetil

Participants in steroid tapering group will take MMF+TAC during the first 18 months. After 18 months, participants without lupus flare will randomly stop MMF or TAC.

Participants in steroid maintenance group will take MMF+TAC during the first 24 months. After 24 months, participants without lupus flare will randomly stop MMF or TAC.

Intervention Type: DRUG

Tacrolimus

Participants in steroid tapering group will take MMF+TAC during the first 18 months. After 18 months, participants without lupus flare will randomly stop MMF or TAC.

Participants in steroid maintenance group will take MMF+TAC during the first 24 months. After 24 months, participants without lupus flare will randomly stop MMF or TAC.

Intervention Type: DRUG

Glucocorticoid

Participants in steroid tapering group will stop taking glucocorticoid after the first 6 months.

Participants in steroid maintenance group will consistently take glucocorticoid for 18 months, and stop the use of glucocorticoid after 18 months if they do not flare.

Intervention Type: DRUG

Other Intervention Names

MMF; TAC

Eligibility Criteria

Inclusion Criteria

• Systemic lupus erythematosus participants diagnosed with 2019 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria, fulfilled with American College of Rheumatology (ACR) lupus nephritis definition, and have reached treatment target (accord with lupus nephritis clinical remission and DORIS) for at least 6 months. The target is defined as: (1)24h urine protein ≤0.5g/d；(2)stable of improved renal function (baseline creatinine ±10% or decrease 15%)；(3)clinical SLE Disease Activity Index (cSLEDAI) =0 (all scores are required zero, except hypocomplementemia and anti-dsDNA antibody positivity)；(4)PGA score (Physician Global Assessment)<0.5; (5)prednisone or equivalent steroid dose≤5mg/d；(6)stable use of immunosuppressants and antimalarial drugs; (7)no use of biological agents.
• According to the physician, the participant can accept this treatment.
• The participant is willing to join this clinical trial, has good compliance, and could understand and sign the informed consent before the study begins.

Exclusion Criteria

• SLE complicated with important organ dysfunction, including consciousness disorder, cognitive disorder, renal dysfunction, heart dysfunction (NYHA class 3, 4), pulmonary arterial hypertension, and interstitial lung disease.
• SLE with active vital organ disease (not satisfied with DORIS), including but not limited to active neuropsychiatric systemic lupus erythematosus, lupus nephritis, thrombocytopenia, hemolytic anemia, myocardial involvement, gastrointestinal involvement, etc.
• Participants who are allergic to or intolerant with mycophenolate mofetil or tacrolimus.
• Participants with acute and chronic infections requiring anti-infective treatment, including but not limited to tuberculosis infection, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection, Human Immunodeficiency Virus (HIV) infection, and Cytomegalovirus (CMV) infection.
• Participants who are pregnant or planning to become pregnant.
• Participants who have used biological agents within 6 months before enrollment.
• The researcher considers any condition that may cause the participant to be unable to complete the study or bring an obvious risk to the participant.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: collaborator

Chinese SLE Treatment And Research Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mengtao Li, MD

Role: STUDY_CHAIR

Peking Union Medical College Hospital

Locations

Peking Union Medical College Hospital

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Can Huang, MD

Role: CONTACT

huang_can@yeah.net

86-13426191948

Facility Contacts

Can Huang, MD

Role: primary

huang_can@yeah.net

86-13426191948

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Other Identifiers

CSTAR008

Identifier Type: -

Identifier Source: org_study_id