Renal Transplantation
Conditions
Keywords
Steroids avoidance,, enteric-coated mycophenolate sodium (EC-MPS),, de novo renal transplantation
Brief summary
This study will investigate the efficacy and safety of a steroid avoidance regimen in comparison with steroid treatment in combination with an initially higher dose of enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine microemulsion in de novo renal transplant recipients. Patients will be randomly allocated to receive either EC-MPS or steroids in combination with EC-MPS. Patients of both treatment groups will receive monoclonal antibody induction therapy and a perioperative bolus of steroids and cyclosporine.
Interventions
DRUGEnteric-coated mycophenolate sodium (EC-MPS)
An initial dose of 1080 mg EC-MPS was administered immediately before transplantation. Then, during the first 6 weeks post-transplantation, EC-MPS was administered at a dose of 1080 mg twice a day 12 hours apart. From week 7 until the end of the study (month 6), EC-MPS was administered at standard dose of 720 mg twice a day.
DRUGPrednisone
Oral tablets
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Primary donor kidney transplant * Panel reactive antibody (PRA) ≤ 20%
Exclusion criteria
* Multi-organ transplantation including dual kidneys or previous transplant with any other organ different from kidney * Non-heart beating donor or kidney from a non-compatible donor Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With the Occurrence of Treatment Failures at 6 Months Post-transplantation | 6 months post transplantation | Treatment failures defined as Biopsy Proven Acute Rejection (BPAR), graft loss, death or loss to follow-up. Only BPAR from other biopsies than the protocol defined biopsy at Month 3 are described. Acute rejection: an episode of acute renal dysfunction diagnosed as rejection on the basis of biopsy or clinical observations, treated with anti-rejection medication. BPAR: renal transplant biopsy finding of acute cellular or antibody mediated rejection. Graft loss: allograft will be presumed to be lost on the day the patient starts dialysis and is not able to subsequently be removed from dialysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | Month 6 | If a participant experienced several BPAR, only the rejection with highest grade is taken into account. Only events that occurred before study treatment discontinuation are taken into account. Only BPAR from other biopsies than the protocol defined biopsy at Month 3 are described. Acute rejection: an episode of acute renal dysfunction diagnosed as rejection on the basis of biopsy or clinical observations, treated with anti-rejection medication. BPAR: renal transplant biopsy finding of acute cellular or antibody mediated rejection. |
| Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Month 3 | A treatment failure is a Biopsy Proven Acute Rejection (BPAR), a graft loss, a death, or a loss to follow-up. Only BPAR from other biopsies than the protocol defined biopsy at Month 3 are described. Acute rejection: an episode of acute renal dysfunction diagnosed as rejection on the basis of biopsy or clinical observations, treated with anti-rejection medication. BPAR: renal transplant biopsy finding of acute cellular or antibody mediated rejection. Graft loss: The allograft will be presumed lost on the day the patient starts dialysis and is not able to subsequently be removed from dialysis. |
| Number of Participants With Subclinical Histological Rejections | Month 3 | The number of participants with subclinical histological rejections was determined by renal biopsy screening at 3 months in 125 patients, providing adequate samples for 112 biopsies. |
| Number of Participants With Treatment Failure at 3 Months by Graft Recovery Status | Month 3 | The number of participants with treatment failure defined as a Biopsy Proven Acute Rejection (BPAR), a graft loss, a death, or a loss to follow-up at 3 months by graft recovery status. Delayed graft function is defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day. Slow graft function is defined as a serum creatinine value \> 250 µmol/L at day 5. |
| Number of Participants Requiring Steroids in Non-steroid Treatment Group | Months 3 and 6 | — |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Without Steroids Patients received Enteric-coated Mycophenolate Sodium (EC-MPS), administered orally 2 times a day for 6 months. Patients also received cyclosporine and a dose of methylprednisolone immediately after transplantation, but did not subsequently receive oral corticosteroids for the remainder of the study. | 112 |
| With Steroids Patients received Enteric-coated Mycophenolate Sodium (EC-MPS), administered orally 2 times a day for 6 months. Patients also received cyclosporine and a dose of methylprednisolone immediately after transplantation, and subsequently continued to receive daily oral prednisone. | 110 |
| Total | 222 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 11 |
| Overall Study | Death | 3 | 5 |
| Overall Study | Graft Loss | 5 | 3 |
| Overall Study | Lack of Efficacy | 11 | 9 |
Baseline characteristics
| Characteristic | Without Steroids | With Steroids | Total |
|---|---|---|---|
| Age Continuous | 51.0 years STANDARD_DEVIATION 10.24 | 50.9 years STANDARD_DEVIATION 11.91 | 51.0 years STANDARD_DEVIATION 11.07 |
| Age, Customized 45-60 years | 56 Participants | 58 Participants | 114 Participants |
| Age, Customized < 45 years | 33 Participants | 25 Participants | 58 Participants |
| Age, Customized >= 60 years | 23 Participants | 27 Participants | 50 Participants |
| Sex: Female, Male Female | 36 Participants | 40 Participants | 76 Participants |
| Sex: Female, Male Male | 76 Participants | 70 Participants | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 104 / 112 | 107 / 110 |
| serious Total, serious adverse events | 72 / 112 | 69 / 110 |
Outcome results
Primary
Number of Participants With the Occurrence of Treatment Failures at 6 Months Post-transplantation
Treatment failures defined as Biopsy Proven Acute Rejection (BPAR), graft loss, death or loss to follow-up. Only BPAR from other biopsies than the protocol defined biopsy at Month 3 are described. Acute rejection: an episode of acute renal dysfunction diagnosed as rejection on the basis of biopsy or clinical observations, treated with anti-rejection medication. BPAR: renal transplant biopsy finding of acute cellular or antibody mediated rejection. Graft loss: allograft will be presumed to be lost on the day the patient starts dialysis and is not able to subsequently be removed from dialysis.
Time frame: 6 months post transplantation
Population: Intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Without Steroids | Number of Participants With the Occurrence of Treatment Failures at 6 Months Post-transplantation | 20 Number of participants |
| With Steroids | Number of Participants With the Occurrence of Treatment Failures at 6 Months Post-transplantation | 16 Number of participants |
Secondary
Number of Participants Requiring Steroids in Non-steroid Treatment Group
Time frame: Months 3 and 6
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Without Steroids | Number of Participants Requiring Steroids in Non-steroid Treatment Group | 3 Months | 25 Number of participants |
| Without Steroids | Number of Participants Requiring Steroids in Non-steroid Treatment Group | 6 Months | 20 Number of participants |
Secondary
Number of Participants With Subclinical Histological Rejections
The number of participants with subclinical histological rejections was determined by renal biopsy screening at 3 months in 125 patients, providing adequate samples for 112 biopsies.
Time frame: Month 3
Population: Intent-to-treat population on whom biopsies were performed at 3 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Without Steroids | Number of Participants With Subclinical Histological Rejections | Sample quality inadequate | 7 Number of participants |
| Without Steroids | Number of Participants With Subclinical Histological Rejections | Subclinical rejection | 12 Number of participants |
| Without Steroids | Number of Participants With Subclinical Histological Rejections | Borderline lesions | 2 Number of participants |
| Without Steroids | Number of Participants With Subclinical Histological Rejections | BPAR | 10 Number of participants |
| With Steroids | Number of Participants With Subclinical Histological Rejections | BPAR | 12 Number of participants |
| With Steroids | Number of Participants With Subclinical Histological Rejections | Sample quality inadequate | 6 Number of participants |
| With Steroids | Number of Participants With Subclinical Histological Rejections | Borderline lesions | 5 Number of participants |
| With Steroids | Number of Participants With Subclinical Histological Rejections | Subclinical rejection | 17 Number of participants |
Secondary
Number of Participants With Treatment Failure at 3 Months by Graft Recovery Status
The number of participants with treatment failure defined as a Biopsy Proven Acute Rejection (BPAR), a graft loss, a death, or a loss to follow-up at 3 months by graft recovery status. Delayed graft function is defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day. Slow graft function is defined as a serum creatinine value \> 250 µmol/L at day 5.
Time frame: Month 3
Population: Intent-to-treat population. N in the categories is the number of participants from the total population that fit into that category for each arm/group. For example: in the Delayed Graft Function category there were 25 participants in the Without steroid group and 24 participants in the With Steroid Group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Without Steroids | Number of Participants With Treatment Failure at 3 Months by Graft Recovery Status | Delayed Graft Function [N= 25,24] | 8 Number of participants |
| Without Steroids | Number of Participants With Treatment Failure at 3 Months by Graft Recovery Status | Slow Graft Function [N= 36,23] | 6 Number of participants |
| Without Steroids | Number of Participants With Treatment Failure at 3 Months by Graft Recovery Status | Immediate Graft Function [N= 51,63] | 3 Number of participants |
| With Steroids | Number of Participants With Treatment Failure at 3 Months by Graft Recovery Status | Delayed Graft Function [N= 25,24] | 4 Number of participants |
| With Steroids | Number of Participants With Treatment Failure at 3 Months by Graft Recovery Status | Slow Graft Function [N= 36,23] | 1 Number of participants |
| With Steroids | Number of Participants With Treatment Failure at 3 Months by Graft Recovery Status | Immediate Graft Function [N= 51,63] | 3 Number of participants |
Secondary
Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months
A treatment failure is a Biopsy Proven Acute Rejection (BPAR), a graft loss, a death, or a loss to follow-up. Only BPAR from other biopsies than the protocol defined biopsy at Month 3 are described. Acute rejection: an episode of acute renal dysfunction diagnosed as rejection on the basis of biopsy or clinical observations, treated with anti-rejection medication. BPAR: renal transplant biopsy finding of acute cellular or antibody mediated rejection. Graft loss: The allograft will be presumed lost on the day the patient starts dialysis and is not able to subsequently be removed from dialysis.
Time frame: Month 3
Population: Intent-to-treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Without Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Graft Loss | 5 Number of participants |
| Without Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Loss to Follow-up | 0 Number of participants |
| Without Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Biopsy Proven Acute Rejection | 10 Number of participants |
| Without Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Acute Rejection | 32 Number of participants |
| Without Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Death | 2 Number of participants |
| Without Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Treated Acute Rejection | 31 Number of participants |
| Without Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Treatment Failure | 17 Number of participants |
| With Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Treated Acute Rejection | 16 Number of participants |
| With Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Treatment Failure | 8 Number of participants |
| With Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Biopsy Proven Acute Rejection | 5 Number of participants |
| With Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Graft Loss | 1 Number of participants |
| With Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Death | 2 Number of participants |
| With Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Loss to Follow-up | 0 Number of participants |
| With Steroids | Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | Acute Rejection | 19 Number of participants |
Secondary
The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months
If a participant experienced several BPAR, only the rejection with highest grade is taken into account. Only events that occurred before study treatment discontinuation are taken into account. Only BPAR from other biopsies than the protocol defined biopsy at Month 3 are described. Acute rejection: an episode of acute renal dysfunction diagnosed as rejection on the basis of biopsy or clinical observations, treated with anti-rejection medication. BPAR: renal transplant biopsy finding of acute cellular or antibody mediated rejection.
Time frame: Month 6
Population: Intent-to-treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Without Steroids | The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | Biopsy Proven Acute Rejection | 13 Number of participants |
| Without Steroids | The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | Graft Loss | 5 Number of participants |
| Without Steroids | The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | Death | 2 Number of participants |
| Without Steroids | The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | Loss to Follow-up | 0 Number of participants |
| Without Steroids | The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | Acute Rejection | 37 Number of participants |
| Without Steroids | The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | Treated Acute Rejection | 36 Number of participants |
| With Steroids | The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | Acute Rejection | 21 Number of participants |
| With Steroids | The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | Biopsy Proven Acute Rejection | 8 Number of participants |
| With Steroids | The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | Loss to Follow-up | 0 Number of participants |
| With Steroids | The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | Graft Loss | 3 Number of participants |
| With Steroids | The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | Treated Acute Rejection | 19 Number of participants |
| With Steroids | The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | Death | 5 Number of participants |