Long-Acting Tacrolimus for the Treatment of Resistant Lupus Nephritis

NCT01206569 | Completed Phase 4

• 1 other identifier: AFKLN
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Lupus Nephritis

Keywords

glomerulonephritis; systemic lupus erythematosus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (1)

advagraf

EXPERIMENTAL

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)

Interventions

Long-acting tacrolimus (Advagraf, Astellas Pharma) DRUG

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

advagraf

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Shatin, Hong Kong

Location

MeSH Terms

Conditions

Lupus Nephritis; Glomerulonephritis; Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 21, 2010
• First Posted: September 22, 2010
• Study Start: September 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: February 1, 2012
• Last Updated: December 4, 2012

Record last verified: 2012-12

Locations

HK (1)