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Trial record 28 of 698 for:    lupus

Efficacy and Safety of Tacrolimus Versus Mycophenolate in Lupus Nephritis

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ClinicalTrials.gov Identifier: NCT02630628
Recruitment Status : Recruiting
First Posted : December 15, 2015
Last Update Posted : May 3, 2018
Sponsor:
Information provided by (Responsible Party):
Professor Daniel Tak-Mao Chan, The University of Hong Kong

Brief Summary:
Prospective, randomized, parallel-group controlled, open-label, international (Asian) multicenter, comparison of corticosteroids combined with TAC and corticosteroids combined with MMF.

Condition or disease Intervention/treatment Phase
Lupus Nephritis Drug: Tacrolimus Drug: Mycophenolate mofetil Phase 4

Detailed Description:
There is accumulating evidence that tacrolimus (TAC) could serve as an effective medication for the treatment of lupus nephritis (LN). TAC is a calcineurin inhibitor, which is a key component in first-line combination immunosuppressive regimens after kidney transplantation, based on its proven efficacy in the prevention and treatment of allograft rejection and acceptable tolerability profile. Although it primarily targets T lymphocyte activation, its immunosuppressive actions encompass multiple immune response pathways due to the complex interactions between different cellular and soluble immune mediators. Moreover, the effect of calcineurin inhibitors on podocyte morphology and function, independent of their immunosuppressive effect, has translated into therapeutic efficacy in the treatment of proteinuric glomerular diseases such as membranous nephropathy and focal segmental glomerulosclerosis. Recent data from short-term studies showed that combination immunosuppressive regimens that included TAC and corticosteroids with or without mycophenolate mofetil (MMF) appeared at least as effective as other standard-of-care treatments for Class III/IV±V LN, and the inclusion of TAC might lead to more effective suppression of proteinuria. There is also preliminary data on its favorable tolerability when used as long-term maintenance treatment. This study aims to examine the role of TAC combined with corticosteroids, in comparison with the most commonly used standard-of-care treatment MMF plus corticosteroids, in the management of lupus nephritis.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Open-label Study to Evaluate the Efficacy and Safety of Tacrolimus and Corticosteroids in Comparison With Mycophenolate Mofetil and Corticosteroids in Subjects With Class III/IV±V Lupus Nephritis
Actual Study Start Date : December 5, 2015
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
Experimental: Tacrolimus
route: oral duration: 96 weeks
Drug: Tacrolimus
Dosage: start at 2mg twice a day, then taper as per protocol
Other Name: Prograf

Active Comparator: Mycophenolate Mofetil
route: oral duration: 96 weeks
Drug: Mycophenolate mofetil
Dosage: start at 1g twice a day, then taper as per protocol
Other Name: Cellcept




Primary Outcome Measures :
  1. Efficacy of combined corticosteroids and TAC compared to combined corticosteroids and MMF in achieving sustained renal response (RR) in patients with active lupus nephritis [Class III/IV±V (LN)] [ Time Frame: 96 weeks ]

    Sustained RR defined as satisfying all of the following criteria:

    1. proteinuria improved by >50% compared with baseline
    2. 24-hr urine protein <1 g
    3. serum creatinine not higher than 15% above baseline level
    4. no occurrence of disease flare, defined as receiving 'rescue' increase of immunosuppressive therapy with any one of the following - requiring increase of prednisolone (or prednisone, or equivalent) dose to above 15 mg/D for 4 weeks or longer, change of originally assigned immunosuppressive agent, or addition of immunosuppressive medications prohibited in protocol



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Biopsy-proven LN Class III/IV±V (ISN/RPS 2003), with biopsy performed within 12 weeks of randomization.
  2. Positive anti-dsDNA.
  3. Active LN with proteinuria (urine protein/creatinine ratio >1.0 or 24-hr urine protein >1.0 g at baseline), with or without hematuria.
  4. Both 'incident' (i.e. new) patients and 'flare' patients can be included.

Exclusion Criteria:

  1. Renal disease unrelated to SLE (e.g. diabetes mellitus, other glomerular or tubulointerstitial disease, renovascular disease), or transplanted kidney.
  2. Estimated glomerular filtration rate (eGFR by MDRD) ≤20 mL/min per 1.73 m2 or serum creatinine >300 micromol/L (3.39 mg/dL) at screening.
  3. Renal biopsy showing cellular or fibrocellular crescent in more than 25% of glomeruli.
  4. CNS or other severe organ manifestation of lupus that necessitate aggressive immunosuppressive therapy on its own.
  5. Co-morbidities that require corticosteroid therapy (e.g. asthma, inflammatory bowel disease).
  6. Treatment with prednisolone (or prednisone, or equivalent) at >20 mg/D for over 4 weeks within the past 3 months.
  7. Treatment with MMF at >1.5 g/D for over 4 weeks within the past 3 months.
  8. Known hypersensitivity or intolerability to prednisolone (or prednisone, or equivalent), TAC, or MMF at a dose of 1.25 g or below per day.
  9. Subjects who are already on treatment with TAC, cyclosporine or any other calcineurin inhibitor for over 4 weeks within the past 12 months.
  10. Treatment with cyclophosphamide, leflunomide, or methotrexate for over 2 weeks, or use of biological agent(s) regardless of duration, within the past 6 months (Note: prior use of azathioprine, mizoribine, intravenous immunoglobulins and anti-malarials is allowed).
  11. Uncontrolled hypertension with systolic BP >160 mmHg or diastolic BP >95 mmHg.
  12. Women who are pregnant or breastfeeding.
  13. Women with childbearing potential or their male partners, who refuse to use an effective birth control method

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02630628


Contacts
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Contact: Tak-Mao Daniel Chan 2255 4542 dtmchan@hku.hk

Locations
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Hong Kong
The University of Hong Kong Recruiting
Hong Kong, Hong Kong
Contact: Tak-Mao Daniel Chan    (852) 2255 4542    dtmchan@hku.hk   
Sponsors and Collaborators
The University of Hong Kong
Investigators
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Principal Investigator: Tak-Mao Daniel Chan The University of Hong Kong

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Responsible Party: Professor Daniel Tak-Mao Chan, Professor, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT02630628     History of Changes
Other Study ID Numbers: ALNN-IIS-17JUL15-1
First Posted: December 15, 2015    Key Record Dates
Last Update Posted: May 3, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Professor Daniel Tak-Mao Chan, The University of Hong Kong:
Lupus Nephritis
mycophenolate mofetil
tacrolimus

Additional relevant MeSH terms:
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Lupus Nephritis
Lupus Erythematosus, Systemic
Nephritis
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Tacrolimus
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents