Lupus NephritisNCT01580865
Comparison Between Tacrolimus (TAC) and Mycophenolate Mofetil (MMF) for Induction of Remission in Lupus Nephritis
A study testing Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus Nephritis in people with Lupus Nephritis, run by Ramathibodi Hospital at 1 site in Thailand.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Lupus Nephritis
- What is being tested?
- Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus Nephritis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 1 siteThailand
- Study dates
- May 2012to Mar 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison Between Tacrolimus and Mycophenolate Mofetil for Induction of Remission in Lupus Nephritis
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.
Read the 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.
- Conditions
- Lupus Nephritis
- Being tested
- Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus Nephritis
- Keywords
- Lupus nephritis, Tacrolimus, Mycophenolate mofetil, Complete remission
- Medical subject headings
- Lupus Nephritis, Pathologic Complete Response
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. . Receives: 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 Receives: Drug: Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus Nephritis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete remission
Return of serum creatinine to previous baseline, plus a decline in the UPCR to <500 mg/g (<50 mg/mmol)
Measured: 1 year
Secondary outcomes (10)
Partial remission
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]
Measured: 1 year
Urine protein to creatinine ratio (UPCR)
g/day
Measured: 1 year
Serum creatinine
mg/dL
Measured: 1 year
Glomerular filtration rate (GFR)
mL/min/1.73m2
Measured: 1 year
Adverse events
Infection, leukopenia, gastrointestinal (GI) symptoms, new onset diabetes mellitus (DM)/hyperglycemia
Measured: 1 year
Serious dverse events
Hospitalization, death
Measured: 1 year
EQ5D
The Euro quality of life -5 Dimensions
Measured: 1 year
SF36
The 36-Item Short Form Health Survey
Measured: 1 year
SLEQOL
Systemic Lupus Erythematosus Quality of Life Questionnaire
Measured: 1 year
SLEDAI-2K
Systemic Lupus Erythematosus Disease Activity Index 2000
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2012 (estimated)
- Study startMay 2012
- Primary completionMar 2017
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lupus NephritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ramathibodi Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- King Chulalongkorn Memorial Hospital, Maharaj Nakorn Chiang Mai Hospital, Department of Medical Services Ministry of Public Health of Thailand, Srinagarind Hospital, Khon Kaen University, Siriraj Hospital, Songklanagarind Hospital
- Responsible party
- Principal investigator, Vasant Sumethkul, Ramathibodi Hospital
- Investigators
- Vasant Sumethkul, Prof., Principal investigator, Ramathibodi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01580865
- Sponsor's protocol ID
- PRG-LN-11-01
- Status last verified
- Sep 2018
- First submitted
- 17 Apr 2012
- Last updated
- 12 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison Between Tacrolimus and Mycophenolate Mofetil for Induction of Remission in Lupus Nephritis
- ClinicalTrials.gov ID
- NCT01580865
- Acronym / sponsor ID
- PRG-LN-11-01
- Conditions
- Lupus Nephritis
- Keywords
- Lupus nephritis, Tacrolimus, Mycophenolate mofetil, Complete remission
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Ramathibodi HospitalUniversity, hospital or other
- Collaborators
- King Chulalongkorn Memorial Hospital, Maharaj Nakorn Chiang Mai Hospital, Department of Medical Services Ministry of Public Health of Thailand, Srinagarind Hospital, Khon Kaen University, Siriraj Hospital, Songklanagarind Hospital
- Study start
- May 2012
- Primary completion
- Mar 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 19 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mycophenolate Mofetil (MMF) | Active comparator | Drug: Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus NephritisMMF 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. . |
| Tacrolimus (TAC) | Experimental | Drug: Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus NephritisTAC 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (17 listed)
- 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
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus NephritisPatients 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. | Drug | Mycophenolate Mofetil (MMF), Tacrolimus (TAC) |
Primary outcome
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)
10 secondary outcomes
Partial remission
Time frame: 1 year
Urine protein to creatinine ratio (UPCR)
Time frame: 1 year
Serum creatinine
Time frame: 1 year
Glomerular filtration rate (GFR)
Time frame: 1 year
Adverse events
Time frame: 1 year
Serious dverse events
Time frame: 1 year
EQ5D
Time frame: 1 year
SF36
Time frame: 1 year
SLEQOL
Time frame: 1 year
SLEDAI-2K
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vasant Sumethkul, Prof. principal investigator
Ramathibodi Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tacrolimus vs. Mycophenolate mofetil for Induction Therapy in Lupus Nephritis in people with Lupus Nephritis, run by Ramathibodi Hospital at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete remission (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2018.