Long-Acting Tacrolimus for the Treatment of Resistant Lupus Nephritis

Study Overview
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Brief Summary
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Glomerulonephritis is one of the major disease manifestations of systemic lupus erythematosus (SLE). Around one-third of the patients, however, do not respond to conventional immunosuppressive therapy, and they have a high risk of progressing to dialysis-dependent renal failure. Recent studies suggest that immunosuppressive therapy targeted against the calcineurin pathway of T-helper cell, for example, tacrolimus, may be effective in the treatment of primary glomerulonephritis. The investigators plan to an open-label single-arm study the efficacy and safety of long-acting tacrolimus in the treatment of treatment-resistant lupus nephritis. Twenty-five patients with biopsy-proven lupus nephritis will be recruited. They will be treated with oral prednisolone and long-acting tacrolimus for 6 months, followed by 6 months of maintenance steroid and azathioprine. Proteinuria, renal function, clinical and serologic lupus activity will be monitored. This study will explore the potential role of long-acting tacrolimus in resistant lupus nephritis, which has a poor prognosis and no effective treatment at the moment.

Official Title
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Long-Acting Tacrolimus for the Treatment of Resistant Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Long-acting tacrolimus (Advagraf, Astellas Pharma)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 18 with informed consent. Fulfill the revised American College of Rheumatology criteria for SLE Biopsy-proven class III, IV, or V lupus nephritis within the past 24 months. Could not achieve complete remission after at least 4 months of conventional therapy (oral steroid plus cyclosphosphamide or mycophenolate mofetil). NB. Complete response is defined as proteinuria less than 0.5 g/day, with normal urinary sediment, a normal serum albumin concentration, and serum creatinine <15% above the base-line value. Female patients of child-bearing age and male patients agree to maintain effective birth control practice during the study. Exclusion Criteria: Abnormal liver function tests Hepatitis B surface antigen or hepatitis C antibody positive Diabetic Receiving NSAID or other agents known to influence urinary Protein excretion Allergic or intolerant to macrolide antibiotics or tacrolimus

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: advagraf<br>Long-acting tacrolimus (Advagraf, Astellas Pharma) will be started at single daily dose of 0.15-0.2 mg/kg/day for 6 months. | Drug: Long-acting tacrolimus (Advagraf, Astellas Pharma)<br>* Long-acting tacrolimus (Advagraf, Astellas Pharma) will be started at single daily dose of 0.15-0.2 mg/kg/day for 6 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall clinical response | complete response is defined as urinary protein < 0.5 g/day, with normal urinary sediment, normal serum albumin, and serum creatinine < 15% above the base-line value. Partial response is defined as urinary protein between 0.6 and 2.9 g/day, with a serum albumin > 30 g/dL, and stable renal function. No response is defined as urinary protein > 3 g/day or a value of 0.6 to 2.9 g/day but serum albumin < 30 g/dL, an increase in serum creatinine ≥ 50 µmol/l or 15% above the base-line value, or the discontinuation of treatment due to side effects. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in SLEDAI score |  | 6 months | 
| 24-hour urinary protein excretion |  | 6 months | 
| renal function |  | 6 months | 
| development of lupus flare (renal or non-renal) |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glomerulonephritis, systemic lupus erythematosus