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

August 28, 2023 updated by: Chinese SLE Treatment And Research Group

Effectiveness of Mycophenolate Mofetil Combined With Tacrolimus for Steroid Tapering in Systemic Lupus Erythematosus: A Prospective, Random Control, Open-label, Single Center Clinical Trial

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 be randomly assigned to therapy with MMF + steroid or TAC + steroid.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

220

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 Locations

  • China
      • Beijing, China, 100730
        • Recruiting
        • Peking Union Medical College Hospital
        • 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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

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: 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
Drug: Mycophenolate Mofetil
During the first 18 months, participants will take MMF+TAC. After 18 months, participants without lupus flare will randomly stop MMF or TAC.
Other Names:
  • MMF
Drug: Tacrolimus
During the first 18 months, participants will take MMF+TAC. After 18 months, participants without lupus flare will randomly stop MMF or TAC.
Other Names:
  • TAC
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.
Active Comparator: steroid maintenance group
0~18th month: mycophenolate mofetil (1g/d) + tacrolimus (2.0mg/d) + steroid (1 pill/d) 18th~30th month: Participants who do not flare will be randomly assigned to therapy with mycophenolate mofetil + steroid (1 pill/d) or tacrolimus + steroid (1 pill/d)
Drug: Mycophenolate Mofetil
During the first 18 months, participants will take MMF+TAC. After 18 months, participants without lupus flare will randomly stop MMF or TAC.
Other Names:
  • MMF
Drug: Tacrolimus
During the first 18 months, participants will take MMF+TAC. After 18 months, participants without lupus flare will randomly stop MMF or TAC.
Other Names:
  • TAC
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 6th~18th month

If the DORIS (Definition of Remission In SLE) is not sustained, the patient is considered to have lupus flare.

Lupus flare can be further evaluated according to SELENA-SLEDAI Flare Index (SFI).

Lupus nephritis flare can be further evaluated as flare of proteinuria and flare of nephritis.
6th~18th month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The 1-year flare rate of lupus nephritis participants who accept MMF or TAC monotherapy.
Time Frame: 18th~30th month
If the DORIS (Definition of Remission In SLE) is not sustained, the patient is considered to have lupus flare.
18th~30th month
Lupus flare (as assessed by SLEDAI and PGA) in SLE patients during the maintenance period after steroid tapering.
Time Frame: 6th~30th month
6th~30th month
The changes of serum activity markers (anti-dsDNA antibody and C3 level) in SLE patients after steroid tapering.
Time Frame: 6th~30th month
6th~30th month
Proportion of SLE patients with irreversible organ damage (assessed by SLICC/SDI) after steroid tapering.
Time Frame: 6th~30th month
6th~30th month
Changes in carotid intima-media thickness after steroid tapering.
Time Frame: 6th~30th month
6th~30th month
Differences in medical charges between steroid tapering and steroid maintenance patients.
Time Frame: 6th~30th month
Obtain the information by questionnaire.
6th~30th month
Differences in health-related quality of life between steroid tapering and steroid maintenance patients.
Time Frame: 6th~30th month
Evaluate health-related quality of life by Short-Form Six-Dimension (SF-6D) health index. SF-6D includes 6 dimensions: physical functioning, role limitations, social functioning, pain, mental health, and vitality. The minimum total value is 0. The maximum total value is 1. Higher scores mean a better outcome.
6th~30th month

Collaborators and Investigators

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

Sponsor

Chinese SLE Treatment And Research Group

Collaborators

Peking Union Medical College Hospital

Investigators

  • Study Chair: Mengtao Li, MD, Peking Union Medical College Hospital

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)

July 1, 2023

Primary Completion (Estimated)

July 31, 2025

Study Completion (Estimated)

July 31, 2026

Study Registration Dates

First Submitted

June 9, 2023

First Submitted That Met QC Criteria

June 21, 2023

First Posted (Actual)

June 23, 2023

Study Record Updates

Last Update Posted (Actual)

August 30, 2023

Last Update Submitted That Met QC Criteria

August 28, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CSTAR008

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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