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Trial record 49 of 906 for:    Lupus

Comparison Between Tacrolimus (TAC) and Mycophenolate Mofetil (MMF) for Induction of Remission in Lupus Nephritis

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ClinicalTrials.gov Identifier: NCT01580865
Recruitment Status : Completed
First Posted : April 19, 2012
Last Update Posted : September 12, 2018
Sponsor:
Collaborators:
King Chulalongkorn Memorial Hospital
Maharaj Nakorn Chiang Mai Hospital
Rajavithi Hospital
Srinagarind Hospital, Khon Kaen University
Siriraj Hospital
Songklanagarind Hospital
Information provided by (Responsible Party):
Vasant Sumethkul, Ramathibodi Hospital

Brief Summary:

Prospective, multi-center, randomized, controlled, trial to compare tacrolimus with mycophenolate mofetil (MMF) for induces complete remission in lupus nephritis patients. The study duration is one year.

Research hypothesis

  • The proportion of patients who have achieved complete remission between regimen of tacrolimus plus prednisolone is greater than MMF plus prednisolone as an induction therapy in lupus nephritis.

Condition or disease Intervention/treatment Phase
Lupus Nephritis Drug: Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus Nephritis Not Applicable

Detailed Description:

The patients with a pathological diagnosis of active lupus nephritis whom are currently followed up or referred to outpatient department (OPD) of 7 participating medical centers in Thailand. Patients who come to attend will be selected according to the inclusion and exclusion criteria.

Outcome measurements

  • The patients will be follow-up for 1 year and will be evaluated for clinical manifestations and laboratory investigations of lupus nephritis and any adverse effects of therapy on each visit.
  • Blood pressure and laboratory assessments, including complete blood cell count, urinalysis, urine protein creatinine ratio (UPCR), and kidney and liver function, will be performed at each visit for 24 weeks and at the end of study (48 weeks).
  • Serum anti-double-stranded DNA antibodies and serum C3 will be measured every 8 weeks after treatment until 24 weeks and at the end of study (48 weeks).
  • A fasting lipid profile will be also measured every 8 weeks until 24 weeks and at the end of study (48 weeks).
  • Renal and extrarenal disease activity of SLE was measured using the SLEDAI2K. The SLEDAI2K will be evaluated at the time of entry into the study and every 8 weeks after treatment until 24 weeks and at the end of study (48 weeks).
  • SLICC damage index, SF-36, EQ5D, and SLEQOL will be evaluated at the time of entry, at 24 weeks, and at the end of the study.
  • Patients' serum and urine (blood 3ml and urine 50 ml) will be collected at baseline, 2nd week, 4th week, 12th week, and 48th week for further analysis of biomarkers in the future.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparison Between Tacrolimus and Mycophenolate Mofetil for Induction of Remission in Lupus Nephritis
Study Start Date : May 2012
Actual Primary Completion Date : March 2017
Actual Study Completion Date : March 2017


Arm Intervention/treatment
Active Comparator: Mycophenolate Mofetil (MMF)
MMF was initiated at a dose of 500 mg twice daily (for patients > 50 Kg and Estimated Glomerular Filtration rate (eGFR) > 60 ml/min) for 2 weeks, and advanced to 750 mg twice daily in LN patients weighing less than 50 kg or 1,000 mg twice daily in LN patients weighing 50 kg or more. .
Drug: Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus Nephritis
Patients were randomly assigned to receive regimen I or II: TAC plus prednisolone (TAC group) or MMF plus prednisolone (MMF group). TAC was started at a dosage of 0.1 mg/kg/day divided into 2 daily doses at 12-hour intervals, and the dosage was titrated to achieve trough blood concentrations of 6-10 ng/mL in the first and second month and then 4-8 ng/mL., thereafter. MMF was initiated at a dose of 500 mg twice daily (for patients > 50 Kg and Estimated Glomerular Filtration rate (eGFR) > 60 ml/min) for 2 weeks, and advanced to 750 mg twice daily in LN patients weighing less than 50 kg or 1,000 mg twice daily in LN patients weighing 50 kg or more. Patients received concomitant prednisone at a dose of 0.5-0.7 mg/kg/d (maximum 60 mg/day), with tapering by 5-10 mg/day every 2 weeks until a dose of 5 mg/d has been achieved, and this dosage was maintained until the end of 24 weeks.

Experimental: Tacrolimus (TAC)
TAC was started at a dosage of 0.1 mg/kg/day divided into 2 daily doses at 12-hour intervals, and the dosage was titrated to achieve trough blood concentrations of 6-10 ng/mL in the first and second month and then 4-8 ng/mL., thereafter
Drug: Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus Nephritis
Patients were randomly assigned to receive regimen I or II: TAC plus prednisolone (TAC group) or MMF plus prednisolone (MMF group). TAC was started at a dosage of 0.1 mg/kg/day divided into 2 daily doses at 12-hour intervals, and the dosage was titrated to achieve trough blood concentrations of 6-10 ng/mL in the first and second month and then 4-8 ng/mL., thereafter. MMF was initiated at a dose of 500 mg twice daily (for patients > 50 Kg and Estimated Glomerular Filtration rate (eGFR) > 60 ml/min) for 2 weeks, and advanced to 750 mg twice daily in LN patients weighing less than 50 kg or 1,000 mg twice daily in LN patients weighing 50 kg or more. Patients received concomitant prednisone at a dose of 0.5-0.7 mg/kg/d (maximum 60 mg/day), with tapering by 5-10 mg/day every 2 weeks until a dose of 5 mg/d has been achieved, and this dosage was maintained until the end of 24 weeks.




Primary Outcome Measures :
  1. Complete remission [ Time Frame: 1 year ]
    Return of serum creatinine to previous baseline, plus a decline in the UPCR to <500 mg/g (<50 mg/mmol)


Secondary Outcome Measures :
  1. Partial remission [ Time Frame: 1 year ]
    Stabilization (±25%), or improvement of serum creatinine, but not to normal, plus a ≥50% decrease in UPCR. If there was nephrotic-range proteinuria (UPCR ≥3000 mg/g [≥300 mg/mmol]), improvement requires a ≥50% reduction in UPCR, and a UPCR <3000 mg/g [<300 mg/mmol]

  2. Urine protein to creatinine ratio (UPCR) [ Time Frame: 1 year ]
    g/day

  3. Serum creatinine [ Time Frame: 1 year ]
    mg/dL

  4. Glomerular filtration rate (GFR) [ Time Frame: 1 year ]
    mL/min/1.73m2

  5. Adverse events [ Time Frame: 1 year ]
    Infection, leukopenia, gastrointestinal (GI) symptoms, new onset diabetes mellitus (DM)/hyperglycemia

  6. Serious dverse events [ Time Frame: 1 year ]
    Hospitalization, death

  7. EQ5D [ Time Frame: 1 year ]
    The Euro quality of life -5 Dimensions

  8. SF36 [ Time Frame: 1 year ]
    The 36-Item Short Form Health Survey

  9. SLEQOL [ Time Frame: 1 year ]
    Systemic Lupus Erythematosus Quality of Life Questionnaire

  10. SLEDAI-2K [ Time Frame: 1 year ]
    Systemic Lupus Erythematosus Disease Activity Index 2000



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient who had biopsy-proven lupus nephritis class III, IV or V according to the International Society of Nephrology (ISN)/Renal Pathology Society (RPS) 2003 classification (ISN/RPS2003) within 16 weeks of randomization and had ANA or anti-dsDNA positive.
  • Laboratory tests documented the presence of active nephritis, defined as proteinuria (protein excretion >1 g/24 h or spot UPCR > 1 for at least two samples) or increased serum creatinine level (>0.3 mg/dL of baseline but less than 2.0 mg/dl) with active urinary sediment (any of >5 red blood cells/high-power field, >5 white blood cells/high-power field, or red blood cell casts in the absence of infection or other causes).
  • Willingness to participate in the study, and be able to read and provide informed consent.

Exclusion Criteria:

  • Severe extra-renal manifestations that may require high-dose steroids or other immunomodulating treatments. The definition of severe extra-renal diseases in this investigation are defined by

    • Active central nervous system deemed to be severe or progressive and/ or associated with significant cognitive impairment leading to inability to provide informed consent and/ or comply with the protocol.
    • Any condition, including clinical findings or the laboratory results, which the investigators consider the patients have high disease activity and need high dose steroid and immunosuppressive drugs or other therapy depending on investigator opinion.
    • Severe myocarditis with congestive heart failure or renal failure.
  • Previous therapy with calcineurin inhibitor or MMF or CYC within the previous 4 months before randomization.
  • Allergy with macrolide antibiotics.
  • Uncontrolled hypertension (systolic blood pressure ≥160mmHg or diastolic blood pressure ≥100mmHg) at screening day.
  • Severely deteriorated renal function or rapid progressive crescentic Glomerulonephritis.
  • Severe myocarditis or cardiomyopathy which may or may not be related to SLE
  • Patients who have thrombotic microangiopathy who require treatment with plasmapheresis or IVIG.
  • Severe infection or active TB.
  • Active hepatitis and evidence of chronic liver disease.
  • HIV infection.
  • Diabetes mellitus.
  • Women who were pregnant or unwilling to use contraception.
  • Patients who response to steroid (complete remission) during the run in period (4 weeks).
  • Known hypersensitivity or contraindication to MMF, mycophenolic acid (MPA), tacrolimus, corticosteroids or any components of these drug products.

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): NCT01580865


Locations
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Thailand
Ramathibodi Hospital
Rahathevi, Bangkok, Thailand, 10400
Sponsors and Collaborators
Ramathibodi Hospital
King Chulalongkorn Memorial Hospital
Maharaj Nakorn Chiang Mai Hospital
Rajavithi Hospital
Srinagarind Hospital, Khon Kaen University
Siriraj Hospital
Songklanagarind Hospital
Investigators
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Principal Investigator: Vasant Sumethkul, Prof. Ramathibodi Hospital

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Responsible Party: Vasant Sumethkul, Prof., Ramathibodi Hospital
ClinicalTrials.gov Identifier: NCT01580865     History of Changes
Other Study ID Numbers: PRG-LN-11-01
First Posted: April 19, 2012    Key Record Dates
Last Update Posted: September 12, 2018
Last Verified: September 2018
Keywords provided by Vasant Sumethkul, Ramathibodi Hospital:
Lupus nephritis
Tacrolimus
Mycophenolate mofetil
Complete remission
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
Mycophenolic Acid
Tacrolimus
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