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This study introduces a new optimization immunosuppressive regimen associating tacrolimus at a reduced dose and enteric-coated mycophenolate sodium at an increased dose in order to slow down renal function worsening and to prevent the progression of chronic allograft nephropathy, while maintaining the same efficacy, in maintenance renal transplant recipients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard dose EC-MPS | Active Comparator | Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus dose (twice a day orally) adjusted to maintain the trough blood level (C0) contained 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 | Experimental | Patients received 1440 mg/day (720 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus dose (twice a day orally) tapered to reach a trough blood level target contained between 2 and 4.5 ng/mL within 15 days after randomization at the most. 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Enteric-coated mycophenolate sodium (EC-MPS) | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Renal Function Assessed by Change in Estimated Glomerular Filtration Rate(eGFR) | 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. | Baseline and Month 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Renal Function at 3 Months Assessed by Change in Estimated Glomerular Filtration Rate (eGFR) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis | Novartis | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis | Basel | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22257543 | Derived | Kamar N, Rostaing L, Cassuto E, Villemain F, Moal MC, Ladriere M, Barrou B, Ducloux D, Chaouche K, Quere S, Di Giambattista F, Be F. A multicenter, randomized trial of increased mycophenolic acid dose using enteric-coated mycophenolate sodium with reduced tacrolimus exposure in maintenance kidney transplant recipients. Clin Nephrol. 2012 Feb;77(2):126-36. doi: 10.5414/CN107227. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Tacrolimus |
| Drug |
|
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| Corticosteroids | Drug | At a dose of at least 5 mg/day. |
|
|
| Baseline and 3 months |
| Number of Participants With Treatment Failure Parameters (Biopsy-Proven Acute Rejection (BPAR), Graft Loss, Death, or Loss to Follow-up) at 6 Months | 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. | 6 months |
| Number of Participants With Graft and Patient Survivals at 6 Months | 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. | 6 months |
| FG001 | 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. |
| Intent-to-treat Population (ITT) |
|
| COMPLETED |
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| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Age, Customized | Number | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Renal Function Assessed by Change in Estimated Glomerular Filtration Rate(eGFR) | 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. | 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. | Posted | Mean | Standard Deviation | mL/min/1.73m^2 | Baseline and Month 6 |
|
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| |||||||||||||||||||||||||||||||||||
| Secondary | Renal Function at 3 Months Assessed by Change in Estimated Glomerular Filtration Rate (eGFR) | 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. | 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. | Posted | Mean | Standard Deviation | mL/min/1.73m^2 | Baseline and 3 months |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Treatment Failure Parameters (Biopsy-Proven Acute Rejection (BPAR), Graft Loss, Death, or Loss to Follow-up) at 6 Months | 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. | 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. | Posted | Number | Participants | 6 months |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Graft and Patient Survivals at 6 Months | 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. | 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. | Posted | Number | Participants | 6 months |
|
6 months
Safety population
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 8 | 47 | 4 | 47 | ||
| EG001 | 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. | 7 | 45 | 10 | 45 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Acute coronary syndrome | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiac disorder | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Ischaemic cardiomyopathy | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Colonic polyp | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Bursitis infective | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pneumocystis jiroveci infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Arteriovenous fistula thrombosis | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Convulsion | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Aortic valve replacement | Surgical and medical procedures | MedDRA | Systematic Assessment |
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| Coronary angioplasty | Surgical and medical procedures | MedDRA | Systematic Assessment |
| |
| Femoral artery aneurysm | Vascular disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Dyslipidaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| ID | Term |
|---|---|
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| D009173 | Mycophenolic Acid |
| D016559 | Tacrolimus |
| D000305 | Adrenal Cortex Hormones |
| D011241 | Prednisone |
| ID | Term |
|---|---|
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D018942 | Macrolides |
| D007783 | Lactones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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| 45-60 |
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| >= 60 |
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| Male |
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| Change from Baseline - Month 6 (n= 45, 43) |
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