Clinical trial NCT01580865: Comparison Between Tacrolimus (TAC) and Mycophenolate Mofetil (MMF) for Induction of Remission in Lupus Nephritis
Official title: Comparison Between Tacrolimus and Mycophenolate Mofetil for Induction of Remission in Lupus Nephritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lupus Nephritis
Keywords: Lupus nephritis
Tacrolimus
Mycophenolate mofetil
Complete remission
Lead sponsor: Ramathibodi Hospital
Sponsor class: OTHER
Collaborators: name: King Chulalongkorn Memorial Hospital
name: Maharaj Nakorn Chiang Mai Hospital
name: Department of Medical Services Ministry of Public Health of Thailand
name: Srinagarind Hospital, Khon Kaen University
name: Siriraj Hospital
name: Songklanagarind Hospital
First posted: 2012-04-19
Enrollment: 84
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Complete remission
timeFrame: 1 year
Secondary outcomes:
measure: Partial remission
timeFrame: 1 year
measure: Urine protein to creatinine ratio (UPCR)
timeFrame: 1 year
measure: Serum creatinine
timeFrame: 1 year
measure: Glomerular filtration rate (GFR)
timeFrame: 1 year
measure: Adverse events
timeFrame: 1 year
measure: Serious dverse events
timeFrame: 1 year
measure: EQ5D
timeFrame: 1 year
measure: SF36
timeFrame: 1 year
measure: SLEQOL
timeFrame: 1 year
measure: SLEDAI-2K
timeFrame: 1 year
Other outcomes:
Locations:
city: Rahathevi
country: Thailand
facility: Ramathibodi Hospital
state: Bangkok
Study officials:
affiliation: Ramathibodi Hospital
name: Vasant Sumethkul, Prof.
role: PRINCIPAL_INVESTIGATOR
References: