Trial Outcomes & Findings for Enteric-coated Mycophenolate Sodium (EC-MPS) With Reduced-dose Tacrolimus Versus EC-MPS With Standard-dose Tacrolimus in Stable Kidney Transplant Recipients (NCT NCT00284934)
NCT ID: NCT00284934
Last Updated: 2011-05-02
Results Overview
Change in estimated glomerular filtration rate from baseline to Month 6 calculated by using abbreviated Modification of Diet in Renal Disease (MDRD) formula. Modification of Diet in Renal Disease (MDRD) formula is: GFR \[mL/min/1.73m\^2\] = 186.3\*(C\^-1.154)\*(A\^-0.203)\*G\*R where -C is the serum concentration of creatinine \[mg/dL\], -A is patient age at sample collection date \[years\], -G=0.742 when gender is female, otherwise G=1, -R=1.21 when race is black, otherwise R=1.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
94 participants
Primary outcome timeframe
Baseline and Month 6
Results posted on
2011-05-02
Participant Flow
Participant milestones
| Measure |
Standard Dose EC-MPS
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
High EC-MPS
Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
|---|---|---|
|
Overall Study
STARTED
|
48
|
46
|
|
Overall Study
Intent-to-treat Population (ITT)
|
47
|
45
|
|
Overall Study
COMPLETED
|
44
|
43
|
|
Overall Study
NOT COMPLETED
|
4
|
3
|
Reasons for withdrawal
| Measure |
Standard Dose EC-MPS
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
High EC-MPS
Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
2
|
|
Overall Study
Other reasons
|
3
|
1
|
Baseline Characteristics
Enteric-coated Mycophenolate Sodium (EC-MPS) With Reduced-dose Tacrolimus Versus EC-MPS With Standard-dose Tacrolimus in Stable Kidney Transplant Recipients
Baseline characteristics by cohort
| Measure |
Standard Dose EC-MPS
n=47 Participants
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
High EC-MPS
n=45 Participants
Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
Total
n=92 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
54.5 Years
STANDARD_DEVIATION 10.4 • n=5 Participants
|
50.7 Years
STANDARD_DEVIATION 12.2 • n=7 Participants
|
52.7 Years
STANDARD_DEVIATION 11 • n=5 Participants
|
|
Age, Customized
< 45
|
11 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Age, Customized
45-60
|
18 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Age, Customized
>= 60
|
18 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Month 6Population: Intent-to-treat (ITT) population was defined as all patients who were randomized and treated with study medication and had at least one post-treatment efficacy assessment.
Change in estimated glomerular filtration rate from baseline to Month 6 calculated by using abbreviated Modification of Diet in Renal Disease (MDRD) formula. Modification of Diet in Renal Disease (MDRD) formula is: GFR \[mL/min/1.73m\^2\] = 186.3\*(C\^-1.154)\*(A\^-0.203)\*G\*R where -C is the serum concentration of creatinine \[mg/dL\], -A is patient age at sample collection date \[years\], -G=0.742 when gender is female, otherwise G=1, -R=1.21 when race is black, otherwise R=1.
Outcome measures
| Measure |
Standard Dose EC-MPS
n=47 Participants
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
High EC-MPS
n=45 Participants
Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
|---|---|---|
|
Renal Function Assessed by Change in Estimated Glomerular Filtration Rate(eGFR)
Baseline (n= 47, 45)
|
45.3 mL/min/1.73m^2
Standard Deviation 9.5
|
56.4 mL/min/1.73m^2
Standard Deviation 11.2
|
|
Renal Function Assessed by Change in Estimated Glomerular Filtration Rate(eGFR)
Month 6 (n= 45, 43)
|
44.7 mL/min/1.73m^2
Standard Deviation 11.5
|
49.1 mL/min/1.73m^2
Standard Deviation 11.11
|
|
Renal Function Assessed by Change in Estimated Glomerular Filtration Rate(eGFR)
Change from Baseline - Month 6 (n= 45, 43)
|
-0.4 mL/min/1.73m^2
Standard Deviation 6.9
|
2.4 mL/min/1.73m^2
Standard Deviation 6.1
|
SECONDARY outcome
Timeframe: Baseline and 3 monthsPopulation: Intent-to-treat (ITT) population was defined as all patients who were randomized and treated with study medication and had at least one post-treatment efficacy assessment.
Change in estimated glomerular filtration rate from baseline to Month 3 calculated by using abbreviated MDRD formula. Modification of Diet in Renal Disease (MDRD) formula is: GFR \[mL/min/1.73m\^2\] = 186.3\*(C\^-1.154)\*(A\^-0.203)\*G\*R where -C is the serum concentration of creatinine \[mg/dL\], -A is patient age at sample collection date \[years\], -G=0.742 when gender is female, otherwise G=1, -R=1.21 when race is black, otherwise R=1.
Outcome measures
| Measure |
Standard Dose EC-MPS
n=47 Participants
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
High EC-MPS
n=45 Participants
Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
|---|---|---|
|
Renal Function at 3 Months Assessed by Change in Estimated Glomerular Filtration Rate (eGFR)
Baseline (n= 47, 45)
|
45.3 mL/min/1.73m^2
Standard Deviation 9.5
|
46.4 mL/min/1.73m^2
Standard Deviation 11.2
|
|
Renal Function at 3 Months Assessed by Change in Estimated Glomerular Filtration Rate (eGFR)
Month 3 (n= 44, 43)
|
44.6 mL/min/1.73m^2
Standard Deviation 10.9
|
48.6 mL/min/1.73m^2
Standard Deviation 10.8
|
|
Renal Function at 3 Months Assessed by Change in Estimated Glomerular Filtration Rate (eGFR)
Change from Baseline to Month 3 (n= 44, 43)
|
-0.4 mL/min/1.73m^2
Standard Deviation 4.6
|
2.1 mL/min/1.73m^2
Standard Deviation 4.9
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Intent-to-treat (ITT) population was defined as all patients who were randomized and treated with study medication and had at least one post-treatment efficacy assessment.
A biopsy-proven acute rejection (BPAR) is defined as a biopsy graded IA, IB, IIA, IIB, or III based on the Banff 1997 classification.The allograft was presumed lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient went through a graft nephrectomy, then the day of nephrectomy was the day of graft loss.
Outcome measures
| Measure |
Standard Dose EC-MPS
n=47 Participants
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
High EC-MPS
n=45 Participants
Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
|---|---|---|
|
Number of Participants With Treatment Failure Parameters (Biopsy-Proven Acute Rejection (BPAR), Graft Loss, Death, or Loss to Follow-up) at 6 Months
Biopsy proven acute rejection
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Failure Parameters (Biopsy-Proven Acute Rejection (BPAR), Graft Loss, Death, or Loss to Follow-up) at 6 Months
Treated acute rejection
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Failure Parameters (Biopsy-Proven Acute Rejection (BPAR), Graft Loss, Death, or Loss to Follow-up) at 6 Months
Graft loss
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Failure Parameters (Biopsy-Proven Acute Rejection (BPAR), Graft Loss, Death, or Loss to Follow-up) at 6 Months
Death
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Intent-to-treat (ITT) population was defined as all patients who were randomized and treated with study medication and had at least one post-treatment efficacy assessment.
Graft survival was defined as the number of patients with no graft loss. The allograft was presumed lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient went through a graft nephrectomy, then the day of nephrectomy was the day of graft loss. Patient survival was defined as the number of patients alive with or without a functioning graft.
Outcome measures
| Measure |
Standard Dose EC-MPS
n=47 Participants
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
High EC-MPS
n=45 Participants
Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
|---|---|---|
|
Number of Participants With Graft and Patient Survivals at 6 Months
Graft survival
|
47 Participants
|
45 Participants
|
|
Number of Participants With Graft and Patient Survivals at 6 Months
Patient survival
|
47 Participants
|
45 Participants
|
Adverse Events
Standard Dose EC-MPS
Serious events: 8 serious events
Other events: 4 other events
Deaths: 0 deaths
High EC-MPS
Serious events: 7 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Standard Dose EC-MPS
n=47 participants at risk
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
High EC-MPS
n=45 participants at risk
Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
|---|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
Cardiac disorders
Acute coronary syndrome
|
2.1%
1/47 • 6 months
Safety population
|
0.00%
0/45 • 6 months
Safety population
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
Cardiac disorders
Cardiac disorder
|
0.00%
0/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
Cardiac disorders
Ischaemic cardiomyopathy
|
0.00%
0/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
Gastrointestinal disorders
Colonic polyp
|
0.00%
0/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
Gastrointestinal disorders
Diarrhoea
|
2.1%
1/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
General disorders
Pyrexia
|
0.00%
0/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
Infections and infestations
Bronchitis
|
0.00%
0/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
Infections and infestations
Bursitis infective
|
2.1%
1/47 • 6 months
Safety population
|
0.00%
0/45 • 6 months
Safety population
|
|
Infections and infestations
Gastroenteritis
|
4.3%
2/47 • 6 months
Safety population
|
0.00%
0/45 • 6 months
Safety population
|
|
Infections and infestations
Pneumocystis jiroveci infection
|
0.00%
0/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
Infections and infestations
Pyelonephritis
|
2.1%
1/47 • 6 months
Safety population
|
0.00%
0/45 • 6 months
Safety population
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula thrombosis
|
2.1%
1/47 • 6 months
Safety population
|
0.00%
0/45 • 6 months
Safety population
|
|
Investigations
Blood creatinine increased
|
0.00%
0/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
Nervous system disorders
Convulsion
|
0.00%
0/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
Nervous system disorders
Presyncope
|
2.1%
1/47 • 6 months
Safety population
|
0.00%
0/45 • 6 months
Safety population
|
|
Renal and urinary disorders
Renal failure
|
2.1%
1/47 • 6 months
Safety population
|
0.00%
0/45 • 6 months
Safety population
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.1%
1/47 • 6 months
Safety population
|
0.00%
0/45 • 6 months
Safety population
|
|
Surgical and medical procedures
Aortic valve replacement
|
0.00%
0/47 • 6 months
Safety population
|
2.2%
1/45 • 6 months
Safety population
|
|
Surgical and medical procedures
Coronary angioplasty
|
2.1%
1/47 • 6 months
Safety population
|
0.00%
0/45 • 6 months
Safety population
|
|
Vascular disorders
Femoral artery aneurysm
|
2.1%
1/47 • 6 months
Safety population
|
0.00%
0/45 • 6 months
Safety population
|
Other adverse events
| Measure |
Standard Dose EC-MPS
n=47 participants at risk
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose adjusted to maintain a trough blood level (C0) between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
High EC-MPS
n=45 participants at risk
Patients received 1440 mg/day (720 mg twice a day orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus (twice a day orally) dose tapered to reach a trough blood level target of between 2 and 4.5 ng/mL within 15 days after randomization. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/47 • 6 months
Safety population
|
6.7%
3/45 • 6 months
Safety population
|
|
Gastrointestinal disorders
Diarrhoea
|
8.5%
4/47 • 6 months
Safety population
|
13.3%
6/45 • 6 months
Safety population
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
0.00%
0/47 • 6 months
Safety population
|
8.9%
4/45 • 6 months
Safety population
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER