Trial record 5 of 107 for:    Open Studies | "Nephritis"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Ramathibodi Hospital
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
ClinicalTrials.gov Identifier:
NCT01580865
First received: April 17, 2012
Last updated: September 25, 2013
Last verified: September 2013
  Purpose

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 Intervention
Lupus Nephritis
Drug: Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus Nephritis

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison Between Tacrolimus and Mycophenolate Mofetil for Induction of Remission in Lupus Nephritis

Resource links provided by NLM:


Further study details as provided by Ramathibodi Hospital:

Primary Outcome Measures:
  • Complete remission [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    urinary protein excretion <0.3 g/24 h with normal urinary sediment, normal serum albumin concentration (serum albumin ≥3.5 g/dL), and stable kidney function (normal serum creatinine range or not >15% more than baseline values)


Secondary Outcome Measures:
  • Partial remission [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    urinary protein excretion range of 0.3-2.9 g/24 h and a decrease of at least 50% of baseline level, with serum albumin concentration of at least 3.0 g/dL and stable kidney function.


Estimated Enrollment: 90
Study Start Date: May 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Mycophenolate Mofetil (MMF)

MMF will be initiated in 45 patients at a dose of 750 mg twice daily (for patients > 50 Kg and eGFR > 60 ml/min), and advanced weekly to a maximum dose of 1,000 mg two times daily to achieve or MPA trough level > 3 mg/dL.

Patients will be received concomitant prednisone at a dose of 1 mg/kg/d (maximum 60 mg/d), with tapering by 5 mg/d every 2 weeks until a dose of 5 mg/d has been achieved, and this dosage will be maintained to the end of 24 weeks

Drug: Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus Nephritis

Tacrolimus will be started in 45 patients at a dosage of 0.05 mg/kg/d divided into 2 daily doses at 12-hour intervals, and the dosage will be titrated to achieve 12-hour trough blood concentrations of 10-20 ng/mL in the first and second month and then 6-8 ng/mL thereafter.

MMF will be initiated in 45 patients at a dose of 750 mg twice daily (for patients > 50 Kg and eGFR > 60 ml/min), and advanced weekly to a maximum dose of 1,000 mg two times daily to achieve or MPA trough level > 3 mg/dL.

All patients will be received concomitant prednisone at a dose of 1 mg/kg/d (maximum 60 mg/d), with tapering by 5 mg/d every 2 weeks until a dose of 5 mg/d has been achieved, and this dosage will be maintained to the end of 24 weeks.

Experimental: Tacrolimus (TAC)

Tacrolimus will be started in 45 patients at a dosage of 0.05 mg/kg/d divided into 2 daily doses at 12-hour intervals, and the dosage will be titrated to achieve 12-hour trough blood concentrations of 10-20 ng/mL in the first and second month and then 6-8 ng/mL thereafter.

Patients will be received concomitant prednisone at a dose of 1 mg/kg/d (maximum 60 mg/d), with tapering by 5 mg/d every 2 weeks until a dose of 5 mg/d has been achieved, and this dosage will be maintained to the end of 24 weeks.

Drug: Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus Nephritis

Tacrolimus will be started in 45 patients at a dosage of 0.05 mg/kg/d divided into 2 daily doses at 12-hour intervals, and the dosage will be titrated to achieve 12-hour trough blood concentrations of 10-20 ng/mL in the first and second month and then 6-8 ng/mL thereafter.

MMF will be initiated in 45 patients at a dose of 750 mg twice daily (for patients > 50 Kg and eGFR > 60 ml/min), and advanced weekly to a maximum dose of 1,000 mg two times daily to achieve or MPA trough level > 3 mg/dL.

All patients will be received concomitant prednisone at a dose of 1 mg/kg/d (maximum 60 mg/d), with tapering by 5 mg/d every 2 weeks until a dose of 5 mg/d has been achieved, and this dosage will be maintained to the end of 24 weeks.


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.
  Eligibility

Genders Eligible for Study:   Both
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01580865

Contacts
Contact: Vasant Sumethkul, Prof. +66818606646 ravsm@mahidol.ac.th

Locations
Thailand
Ramathibodi Hospital Recruiting
Rahathevi, Bangkok, Thailand, 10400
Contact: Vasant Sumethkul    +66818606646    ravsm@mahidol.ac.th   
Principal Investigator: Vasant Sumethkul, Prof.         
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
Principal Investigator: Vasant Sumethkul, Prof. Ramathibodi Hospital
  More Information

No publications provided

Responsible Party: Vasant Sumethkul, Prof., Ramathibodi Hospital
ClinicalTrials.gov Identifier: NCT01580865     History of Changes
Other Study ID Numbers: PRG-LN-11-01
Study First Received: April 17, 2012
Last Updated: September 25, 2013
Health Authority: Thailand: Ministry of Public Health

Keywords provided by Ramathibodi Hospital:
Lupus nephritis
Tacrolimus
Mycophenolate mofetil
Complete remission

Additional relevant MeSH terms:
Lupus Nephritis
Nephritis
Glomerulonephritis
Kidney Diseases
Urologic Diseases
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Mycophenolate mofetil
Mycophenolic Acid
Tacrolimus
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014