Clinical trial NCT05916781: Effectiveness of Mycophenolate Mofetil Combined With Tacrolimus for Steroid Tapering in Systemic Lupus Erythematosus
Official title: Effectiveness of Mycophenolate Mofetil Combined With Tacrolimus for Steroid Tapering in Systemic Lupus Erythematosus: A Prospective, Random Control, Open-label, Single Center Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Systemic Lupus Erythematosus
Lupus Nephritis
Keywords: mycophenolate mofetil
tacrolimus
steroid tapering
systemic lupus erythematosus
lupus nephritis
Lead sponsor: Chinese SLE Treatment And Research Group
Sponsor class: OTHER
Collaborators: name: Peking Union Medical College Hospital
First posted: 2023-06-23
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: First, participants are randomly assigned into 2 groups: steroid tapering group and steroid maintenance group. In steroid tapering group, participants without flare will be assigned into 2 groups: mycophenolate mofetil group and tacrolimus group. In steroid maintenance group, participants without flare will stop the use of steroid for 6 months. Participants without lupus flare after the stop of steroid will be assigned into 2 groups: mycophenolate mofetil group and tacrolimus group.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The 1-year flare rate of lupus nephritis participants who reach the treatment target and accept MMF+TAC remedy tapering steroid in the maintenance period.
timeFrame: 6th~18th month
Secondary outcomes:
measure: The 1-year flare rate of lupus nephritis participants who accept MMF or TAC monotherapy.
timeFrame: 18th~30th month
measure: Lupus flare (as assessed by SLEDAI and PGA) in SLE patients during the maintenance period after steroid tapering.
timeFrame: 6th~30th month
measure: The changes of serum activity markers (anti-dsDNA antibody and C3 level) in SLE patients after steroid tapering.
timeFrame: 6th~30th month
measure: Proportion of SLE patients with irreversible organ damage (assessed by SLICC/SDI) after steroid tapering.
timeFrame: 6th~30th month
measure: Changes in carotid intima-media thickness after steroid tapering.
timeFrame: 6th~30th month
measure: Differences in medical charges between steroid tapering and steroid maintenance patients.
timeFrame: 6th~30th month
measure: Differences in health-related quality of life between steroid tapering and steroid maintenance patients.
timeFrame: 6th~30th month
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
affiliation: Peking Union Medical College Hospital
name: Mengtao Li, MD
role: STUDY_CHAIR
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