Renal Transplantation
Conditions
Keywords
enteric-coated mycophenolate sodium, everolimus, CNI-free regimen
Brief summary
Calcineurin inhibitors (CNI), a potent immunosuppressive drug used in kidney transplant recipients to prevent graft rejection, may cause renal impairment. The aim of this study is to assess whether a CNI-free regimen with enteric-coated mycophenolate sodium and everolimus is as safe and well tolerated as a standard regimen consisting of enteric-coated mycophenolate sodium and cyclosporine microemulsion without a compromise in therapeutic efficacy while resulting in an improved renal function.
Interventions
DRUGEverolimus
Participants, switching from the CsA based treatment, initially received everolimus 1.5 mg/day and then from day 7, 3 mg/day, and then from day 14, the dose was based on the participants' blood level (6-10 ng/ml). Participants, switching from the tacrolimus based treatment, initially received 3 mg/day and then from day 14, the dose was based on the participants' blood level (6-10 ng/ml).
The dose was based on the participants' blood level of C0h (80-150 ng/ml).
DRUGTacrolimus
The dose was based on the participants' blood level of C0h (5-10 ng/ml).
DRUGEnteric Coated - Mycophenolate Sodium (EC-MPS)
The dose was ≥ 720 mg/day.
DRUGCorticosteroids
Corticosteroids were given according to local standard and/or the Investigators' discretion.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Males or females, aged \> 18 years, Maintenance renal transplant recipients at least 6 months post-transplantation, Patients with a serum creatinine \< 2,5 mg/dL stable for at least three month (according to the investigator), Females capable of becoming pregnant had to have a negative serum pregnancy test within seven days prior to or at baseline, and were required to practice an approved method of birth control for the duration of the study and for a period of six weeks following discontinuation of study medication, even where there had been a history of infertility, Patients receiving Myfortic® (Myfortic dose . 720 mg/d) and Sandimmun® Optoral with or without corticosteroids as part of their immunosuppressive regimen for at least 1 month before baseline;
Exclusion criteria
More than one previous renal transplantation, Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney, Patient with proteinuria \> 1000 mg/day at baseline, Hypersensitivity to Certican®, Sandimmun® Optoral, Prograf®, mycophenolic acid, or other components of the formulation, Patients who had received an investigational drug within four weeks prior to baseline, Severe rejection (≥ Banff II acute rejection), recurrent acute rejection, or steroid resistant rejection within six months of enrollment, Thrombocytopenia (platelets \< 100,000/mm³), with an absolute neutrophil count of \< 1,500/mm³ or leukopenia (leukocytes \< 4,000/mm³), or hemoglobin \< 8 g/dL, Abnormal physical or laboratory findings of clinical significance within two weeks of study inclusion which at the investigator's discretion would interfere with the objectives of the study, Symptoms of significant somatic or mental illness. Inability to cooperate or communicate with the investigator, or patients who were unlikely to comply with the study requirements, or who were unable to give informed consent, History of malignancy during the last five years, except squamous or basal cell carcinoma of the skin, Patients who were HIV positive, or hepatitis C, or hepatitis B surface antigen positiveEvidence of severe liver disease (including abnormal liver enzyme profile, i.e. aspartate transaminase (AST), alanine aminotransferase (ALT) or total bilirubin \> 3 times upper limit of normal (ULN), Females of childbearing potential who were planning to become pregnant, who were pregnant or lactating and/or who were unwilling to use effective means of contraception, Presence of a clinically significant infection requiring continued therapy, severe diarrhea, active peptic ulcer disease or uncontrolled diabetes mellitus that in the opinion of the investigator would interfere with the appropriate conduct of the study, Evidence of drug or alcohol abuse Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Renal Function | 12 months | The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biopsy Proven Acute Rejection, Graft Loss, and Death | 12 months | The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment. |
| Occurrence of Treatment Failures | 12 months | The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment. |
| Evolution of Renal Function | Baseline, 12 months | The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment. |
| Number of Participants Who Experienced Adverse Events and Death | 12 months | Participants were monitored for adverse events, serious adverse events and deaths thorughout the prospective and follow-up phases of the study. |
| Changes in Cardiovascular Risk | Baseline, 12 months | The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment. |
| Changes in Proteinuria | Baseline, 12 months | The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment. |
Countries
Germany
Participant flow
Recruitment details
Renal transplant recipients at least 6 months post transplantation were randomized to the CNI group or Certican group. Post 12 months, participants entered a follow-up phase for an additional 48 months. Thirty-three participants in the CNI group and 34 participants in the Certican group had a month 60 follow-up status.
Participants by arm
| Arm | Count |
|---|---|
| Calcineurin Inhibitor (CNI) Group Participants received Cyclosporine A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids, or Tacrolimus A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids. | 47 |
| Certican Group Participants were switched in a step-wise fashion from the CNI based regimen to Everolimus (RAD001). | 46 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Core (Months 0 - 12) | Administrative problems | 1 | 1 |
| Core (Months 0 - 12) | Adverse Event | 5 | 15 |
| Core (Months 0 - 12) | Protocol deviation | 1 | 1 |
| Core (Months 0 - 12) | Withdrawal by Subject | 3 | 1 |
| Follow-up (Months 12 - 60) | Death | 1 | 1 |
| Follow-up (Months 12 - 60) | Lost to Follow-up | 2 | 1 |
| Follow-up (Months 12 - 60) | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Calcineurin Inhibitor (CNI) Group | Certican Group | Total |
|---|---|---|---|
| Age, Continuous | 49.8 Years STANDARD_DEVIATION 11.1 | 51.0 Years STANDARD_DEVIATION 10.3 | 50.4 Years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 12 Participants | 17 Participants | 29 Participants |
| Sex: Female, Male Male | 35 Participants | 29 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 47 | 41 / 46 |
| serious Total, serious adverse events | 11 / 47 | 12 / 46 |
Outcome results
Primary
Renal Function
The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Time frame: 12 months
Secondary
Biopsy Proven Acute Rejection, Graft Loss, and Death
The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Time frame: 12 months
Secondary
Changes in Cardiovascular Risk
The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Time frame: Baseline, 12 months
Secondary
Changes in Proteinuria
The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Time frame: Baseline, 12 months
Secondary
Evolution of Renal Function
The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Time frame: Baseline, 12 months
Secondary
Number of Participants Who Experienced Adverse Events and Death
Participants were monitored for adverse events, serious adverse events and deaths thorughout the prospective and follow-up phases of the study.
Time frame: 12 months
Population: The safety set, which included all randomized participants, comprised the analysis population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Calcineurin Inhibitor (CNI) Group | Number of Participants Who Experienced Adverse Events and Death | Adverse events (serious and non-serious) | 44 Participants |
| Calcineurin Inhibitor (CNI) Group | Number of Participants Who Experienced Adverse Events and Death | Serious adverse events | 11 Participants |
| Calcineurin Inhibitor (CNI) Group | Number of Participants Who Experienced Adverse Events and Death | Deaths | 1 Participants |
| Certican Group | Number of Participants Who Experienced Adverse Events and Death | Adverse events (serious and non-serious) | 44 Participants |
| Certican Group | Number of Participants Who Experienced Adverse Events and Death | Serious adverse events | 12 Participants |
| Certican Group | Number of Participants Who Experienced Adverse Events and Death | Deaths | 1 Participants |
Secondary
Occurrence of Treatment Failures
The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Time frame: 12 months