Long-Acting Tacrolimus for the Treatment of Resistant Lupus Nephritis

Phase 4CompletedNCT01206569

Chinese University of Hong Kong2 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Lupus Nephritis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 6 months

Secondary Outcomes

change in SLEDAI score

Time frame: 6 months

24-hour urinary protein excretion

Time frame: 6 months

renal function

Time frame: 6 months

development of lupus flare (renal or non-renal)

Time frame: 6 months

Long-Acting Tacrolimus for the Treatment of Resistant Lupus Nephritis

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes