Long-Acting Tacrolimus for the Treatment of Resistant Lupus Nephritis

Phase 4

Completed

• Conditions: Lupus Nephritis
• Interventions: Drug: Long-acting tacrolimus (Advagraf, Astellas Pharma)

• Registration Number: NCT01206569
• Lead Sponsor: Chinese University of Hong Kong

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-09
• Study First Submitted: 2010-09-21
• Study First Submitted QC: 2010-09-21
• Study First Posted: 2010-09-22
• Primary Completion: 2011-12
• Study Completion: 2012-02
• Status Verified: 2012-12
• Last Update Submitted: 2012-12-03
• Last Update Posted: 2012-12-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2

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.

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
advagraf	Long-acting tacrolimus (Advagraf, Astellas Pharma)	Long-acting tacrolimus (Advagraf, Astellas Pharma) will be started at single daily dose of 0.15-0.2 mg/kg/day for 6 months.

Primary Outcome Measures

Name	Time	Method
overall clinical response	6 months	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.

Secondary Outcome Measures

Name	Time	Method
renal function	6 months
change in SLEDAI score	6 months
24-hour urinary protein excretion	6 months
development of lupus flare (renal or non-renal)	6 months

Trial Locations

Locations (1)

Prince of Wales Hospital; 🇭🇰 Shatin, Hong Kong