NCT01580865

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
84

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started May 2012

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 17, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 19, 2012

Completed
12 days until next milestone

Study Start

First participant enrolled

May 1, 2012

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2017

Completed
Last Updated

September 12, 2018

Status Verified

September 1, 2018

Enrollment Period

4.8 years

First QC Date

April 17, 2012

Last Update Submit

September 10, 2018

Conditions

Lupus Nephritis

Keywords

Lupus nephritisTacrolimusMycophenolate mofetilComplete remission

Outcome Measures

Primary Outcomes (1)

  • Complete remission

    Return of serum creatinine to previous baseline, plus a decline in the UPCR to \<500 mg/g (\<50 mg/mmol)

    1 year

Secondary Outcomes (10)

  • Partial remission

    1 year

  • Urine protein to creatinine ratio (UPCR)

    1 year

  • Serum creatinine

    1 year

  • Glomerular filtration rate (GFR)

    1 year

  • Adverse events

    1 year

  • +5 more secondary outcomes

Study Arms (2)

Mycophenolate Mofetil (MMF)

ACTIVE COMPARATOR

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

Tacrolimus (TAC)

EXPERIMENTAL

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

Interventions

Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus NephritisDRUG

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.

Mycophenolate Mofetil (MMF)Tacrolimus (TAC)

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ramathibodi Hospital

Rahathevi, Bangkok, 10400, Thailand

Location

MeSH Terms

Conditions

Lupus NephritisPathologic Complete Response

Interventions

Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

GlomerulonephritisNephritisKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesLupus Erythematosus, SystemicConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System DiseasesDisease ProgressionDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Combined Modality TherapyTherapeutics

Study Officials

  • Vasant Sumethkul, Prof.

    Ramathibodi Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof.

Study Record Dates

First Submitted

April 17, 2012

First Posted

April 19, 2012

Study Start

May 1, 2012

Primary Completion

March 1, 2017

Study Completion

March 1, 2017

Last Updated

September 12, 2018

Record last verified: 2018-09

Locations

TH(1)