Disorder Related to Cardiac Transplantation
Conditions
Keywords
thoracic transplant recipients, everolimus, immunosuppressants
Brief summary
This study investigated whether initiation of everolimus together with reduction of calcineurin inhibitors (CNI) in maintenance heart or lung transplant patients with renal impairment would improve renal function.
Interventions
DRUGEverolimus
0.75-1.5 mg twice daily. At the week 1 visit and thereafter, the dose was adjusted to target blood concentration in the range 3-8 ng/mL.
DRUGMycophenolic acid (MPA)/azathioprine (AZA)
In the standard CNI arm, all immunosuppressants including (MPA) and azathioprine (AZA) continued unchanged as per local practice.
Calcineurin inhibitors include cyclosporine, pimecrolimus, and tacrolimus.
DRUGSteroids
Steroid treatment was according to local practice. If steroids were given, the baseline dose of prednisone or equivalent was to be kept unchanged for all treatment groups for the total study duration, unless a medical condition dictated a change.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients who have undergone a heart or lung transplantation more than 12 months ago. * Patients receiving Neoral® or Prograf®. * Patients with a measured or calculated glomerular filtration rate (GFR) \> 20 and \< 70 mL/min/1.73m\^2. For patients with a GFR \> 60 and \< 70 mL/min/1.73m\^2, a deteriorated renal function since the time of transplantation must be documented by at least one post-transplant GFR level that is \> 10% above the GFR level at the time of inclusion. * Patients willing and capable of giving written informed consent for study participation and able to participate in the study for 12 months. * Females of potential childbearing age must have a negative serum pregnancy test within 7 days prior to enrollment. Effective contraception must be used during the trial and for 6 weeks following discontinuation of the study medication, even where there has been a history of infertility.
Exclusion criteria
* Patients who are recipients of multiple organ transplants. * Patients with measured GFR \< 20 mL/min/1.73m\^2 or \> 70 mL/min/1.73m\^2. * Patients with a treated acute rejection episode within the last 3 months. * Patients with a platelet count of \< 50,000/mm\^3 or with a white blood cell count of ≤ 2,500/mm\^3 or with a hemoglobin value \< 8 g/dL. * Presence of severe hypercholesterolemia (≥ 8.0 mmol/L) or hypertriglyceridemia (≥ 6.0 mmol/L) despite conventional lipid lowering treatment. * Patients currently treated or who have been treated with a mammalian target of rapamycin (mTOR) inhibitor. * Patients who have received an investigational drug within 4 weeks. * Patients who are human immunodeficiency virus positive or who have a current severe systemic infection requiring continued therapy according to investigator judgment. * Present use of any immunosuppressive drugs other than Neoral®/Prograf®, mycophenolic acid/azathioprine (MPA/AZA), and/or steroids. * Patients with a known hypersensitivity to drugs similar to everolimus. * Symptoms of significant mental illness which, in the opinion of the investigator, may interfere with the patient's ability to comply with the protocol. History of drug or alcohol abuse within 1 year of baseline. * Inability to cooperate or communicate with the investigator. * Patients with any past (within the last 5 years) or present malignancy other than excised squamous or basal cell carcinoma. * Females of childbearing potential that are planning to become pregnant, who are pregnant and/or lactating, or who are unwilling to use effective means of contraception. * Patients with a planned coronary revascularization or patients who have experienced a major adverse cardiovascular event (MACE) within the last 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12 | Baseline to Month 12 | Renal function was assessed by determining the measured glomerular filtration rate (mGFR) using creatinine ethylenediamine tetraacetic acid (Cr-EDTA) clearance or an equivalent method. A positive change score indicates improved renal function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Creatinine From Baseline to End of Study (Month 24) | Baseline to end of study (Month 24) | Renal function was assessed by determining serum creatinine using standard laboratory methods. A positive change score indicates improved renal function. |
| Number of Patients With Biopsy-proven Acute Rejection From Month 12 to End of Study (Month 24) | Month 12 to end of study (Month 24) | Biopsy-proved acute rejection was defined as a treated acute rejection confirmed by biopsy, graded locally according to the International Society for Heart & Lung Transplantation (ISHLT) criteria. A treated acute rejection was defined as an acute rejection clinically suspected, whether biopsy-proven or not, which had been treated and confirmed by the investigator according to the response to therapy. |
| Number of Patients Who Died and Number of Patients With Graft Loss From Month 12 to End of Study (Month 24) | Month 12 to end of study (Month 24) | Number of patients not alive and number of patients with loss of their graft. |
| Number of Patients in Need of Dialysis From Month 12 to End of Study (Month 24) | Month 12 to end of study (Month 24) | — |
| Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup | Baseline to end of study (Month 24) | Forced expiratory volume in 1 second (FEV1) was measured by spirometry conducted according to internationally accepted standards. FEV1 is the volume delivered in the first second of a forced vital capacity (FVC) maneuver. A positive change score indicates improved lung function. |
| Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24) | Baseline to end of study (Month 24) | Renal function was assessed by determining the measured glomerular filtration rate (mGFR) using creatinine ethylenediamine tetraacetic acid (Cr-EDTA) clearance or an equivalent method. A positive change score indicates improved renal function. |
| Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | Baseline to end of study (Month 24) | Left ventricular function was assessed by echocardiography which was performed according to local routine practice. Echocardiography parameters were left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), interventricular septal wall thickness (IVSTd), and posterior wall thickness (PWTd). A positive change score indicates improved left ventricular function. |
| Change in Left Ventricular Function (Filling and Ejection Fraction Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | Baseline to end of study (Month 24) | Left ventricular function was assessed by echocardiography which was performed according to local routine practice. Echocardiography parameters were filling fraction (FF) and ejection fraction (EF). A positive change score indicates improved left ventricular function. |
| Mean Days of Hospitalization From Baseline to End of Study (Month 24) | Baseline to end of study (Month 24) | — |
| Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Month 12 to end of study (Month 24) | — |
| Change in Forced Vital Capacity (FVC) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup | Baseline to end of study (Month 24) | Forced vital capacity (FVC) was measured by spirometry conducted according to internationally accepted standards. FVC is the volume delivered during an expiration made as forcefully and completely as possible starting from full inspiration. A positive change score indicates improved lung function. |
Countries
Denmark, Norway, Sweden
Participant flow
Recruitment details
This was a 12-month study in maintenance heart and lung transplant patients with a follow-up period of an additional 12 months. Results to 24 months are presented. Patients were randomized to continue their current calcineurin inhibitors (CNI) based regimen or to start everolimus with reduction of CNI blood levels.
Participants by arm
| Arm | Count |
|---|---|
| Everolimus + CNI Reduction Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level \< 75 ng/mL or a tacrolimus trough level \< 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | 140 |
| Control CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. | 142 |
| Total | 282 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Core Study: 0-12 Months | Administrative Reason | 1 | 1 |
| Core Study: 0-12 Months | Adverse Event | 18 | 2 |
| Core Study: 0-12 Months | Death | 3 | 0 |
| Core Study: 0-12 Months | Unspecified reasons | 1 | 4 |
| Core Study: 0-12 Months | Withdrew Consent | 5 | 2 |
| Extension Study: 12-24 Months | Abnormal laboratory value | 1 | 0 |
| Extension Study: 12-24 Months | Adverse Event | 8 | 0 |
| Extension Study: 12-24 Months | Death | 1 | 1 |
| Extension Study: 12-24 Months | Unspecified reason | 0 | 3 |
Baseline characteristics
| Characteristic | Everolimus + CNI Reduction | Control | Total |
|---|---|---|---|
| Age, Continuous | 59.2 years STANDARD_DEVIATION 9.5 | 56.4 years STANDARD_DEVIATION 10.7 | 57.8 years STANDARD_DEVIATION 9.96 |
| Sex: Female, Male Female | 37 Participants | 40 Participants | 77 Participants |
| Sex: Female, Male Male | 103 Participants | 102 Participants | 205 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 48 / 96 | 75 / 94 | 33 / 46 | 42 / 46 | 33 / 86 | 29 / 69 | 21 / 41 | 27 / 39 |
| serious Total, serious adverse events | 23 / 96 | 40 / 94 | 17 / 46 | 25 / 46 | 31 / 86 | 25 / 69 | 21 / 41 | 16 / 39 |
Outcome results
Primary
Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12
Renal function was assessed by determining the measured glomerular filtration rate (mGFR) using creatinine ethylenediamine tetraacetic acid (Cr-EDTA) clearance or an equivalent method. A positive change score indicates improved renal function.
Time frame: Baseline to Month 12
Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Everolimus + CNI Reduction | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12 | Baseline | 48.6 mL/min | Standard Deviation 15.1 |
| Everolimus + CNI Reduction | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12 | Month 12 | 53.2 mL/min | Standard Deviation 15.7 |
| Everolimus + CNI Reduction | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12 | Change from Baseline | 4.6 mL/min | Standard Deviation 10.4 |
| Control | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12 | Baseline | 48.0 mL/min | Standard Deviation 13.2 |
| Control | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12 | Month 12 | 47.5 mL/min | Standard Deviation 16.1 |
| Control | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12 | Change from Baseline | -0.5 mL/min | Standard Deviation 9 |
Secondary
Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup
Forced expiratory volume in 1 second (FEV1) was measured by spirometry conducted according to internationally accepted standards. FEV1 is the volume delivered in the first second of a forced vital capacity (FVC) maneuver. A positive change score indicates improved lung function.
Time frame: Baseline to end of study (Month 24)
Population: Patients in the lung transplant subgroup of the intent-to-treat (ITT) population which included all randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Everolimus + CNI Reduction | Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup | -0.2 Liters | Standard Deviation 0.2 |
| Control | Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup | -0.1 Liters | Standard Deviation 0.2 |
Secondary
Change in Forced Vital Capacity (FVC) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup
Forced vital capacity (FVC) was measured by spirometry conducted according to internationally accepted standards. FVC is the volume delivered during an expiration made as forcefully and completely as possible starting from full inspiration. A positive change score indicates improved lung function.
Time frame: Baseline to end of study (Month 24)
Population: Patients in the lung transplant subgroup of the intent-to-treat (ITT) population which included all randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Everolimus + CNI Reduction | Change in Forced Vital Capacity (FVC) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup | -0.2 Liters | Standard Deviation 0.3 |
| Control | Change in Forced Vital Capacity (FVC) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup | -0.1 Liters | Standard Deviation 0.4 |
Secondary
Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup
Left ventricular function was assessed by echocardiography which was performed according to local routine practice. Echocardiography parameters were left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), interventricular septal wall thickness (IVSTd), and posterior wall thickness (PWTd). A positive change score indicates improved left ventricular function.
Time frame: Baseline to end of study (Month 24)
Population: Patients in the heart transplant subgroup of the intent-to-treat (ITT) population which included all randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Everolimus + CNI Reduction | Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | LVEDD | -0.1 cm | Standard Deviation 0.8 |
| Everolimus + CNI Reduction | Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | LVESD | 0.1 cm | Standard Deviation 0.7 |
| Everolimus + CNI Reduction | Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | IVSTd | -0.4 cm | Standard Deviation 2.4 |
| Everolimus + CNI Reduction | Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | PWTd | -0.5 cm | Standard Deviation 2.1 |
| Control | Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | PWTd | -0.1 cm | Standard Deviation 1.1 |
| Control | Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | LVEDD | -0.0 cm | Standard Deviation 0.4 |
| Control | Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | IVSTd | -0.1 cm | Standard Deviation 1.2 |
| Control | Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | LVESD | 0.1 cm | Standard Deviation 0.6 |
Secondary
Change in Left Ventricular Function (Filling and Ejection Fraction Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup
Left ventricular function was assessed by echocardiography which was performed according to local routine practice. Echocardiography parameters were filling fraction (FF) and ejection fraction (EF). A positive change score indicates improved left ventricular function.
Time frame: Baseline to end of study (Month 24)
Population: Patients in the heart transplant subgroup of the intent-to-treat (ITT) population which included all randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Everolimus + CNI Reduction | Change in Left Ventricular Function (Filling and Ejection Fraction Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | FF | 0 percentage | Standard Deviation 1 |
| Everolimus + CNI Reduction | Change in Left Ventricular Function (Filling and Ejection Fraction Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | EF | -0.6 percentage | Standard Deviation 8.5 |
| Control | Change in Left Ventricular Function (Filling and Ejection Fraction Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | EF | 0.1 percentage | Standard Deviation 7.9 |
| Control | Change in Left Ventricular Function (Filling and Ejection Fraction Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup | FF | 0 percentage | Standard Deviation 1 |
Secondary
Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24)
Renal function was assessed by determining the measured glomerular filtration rate (mGFR) using creatinine ethylenediamine tetraacetic acid (Cr-EDTA) clearance or an equivalent method. A positive change score indicates improved renal function.
Time frame: Baseline to end of study (Month 24)
Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Everolimus + CNI Reduction | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24) | Month 0 | 49.3 mL/min | Standard Deviation 14.7 |
| Everolimus + CNI Reduction | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24) | Month 24 | 52.5 mL/min | Standard Deviation 16.4 |
| Everolimus + CNI Reduction | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24) | Change | 3.2 mL/min | Standard Deviation 12.3 |
| Control | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24) | Month 0 | 49.1 mL/min | Standard Deviation 13 |
| Control | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24) | Month 24 | 46.8 mL/min | Standard Deviation 15.2 |
| Control | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24) | Change | -2.4 mL/min | Standard Deviation 9 |
Secondary
Change in Serum Creatinine From Baseline to End of Study (Month 24)
Renal function was assessed by determining serum creatinine using standard laboratory methods. A positive change score indicates improved renal function.
Time frame: Baseline to end of study (Month 24)
Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Everolimus + CNI Reduction | Change in Serum Creatinine From Baseline to End of Study (Month 24) | Month 0 | 126 μmol/L | Standard Deviation 30 |
| Everolimus + CNI Reduction | Change in Serum Creatinine From Baseline to End of Study (Month 24) | Month 24 | 126 μmol/L | Standard Deviation 64 |
| Everolimus + CNI Reduction | Change in Serum Creatinine From Baseline to End of Study (Month 24) | Change | 0 μmol/L | Standard Deviation 53 |
| Control | Change in Serum Creatinine From Baseline to End of Study (Month 24) | Month 0 | 129 μmol/L | Standard Deviation 29 |
| Control | Change in Serum Creatinine From Baseline to End of Study (Month 24) | Month 24 | 132 μmol/L | Standard Deviation 37 |
| Control | Change in Serum Creatinine From Baseline to End of Study (Month 24) | Change | 3 μmol/L | Standard Deviation 23 |
Secondary
Mean Days of Hospitalization From Baseline to End of Study (Month 24)
Time frame: Baseline to end of study (Month 24)
Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Everolimus + CNI Reduction | Mean Days of Hospitalization From Baseline to End of Study (Month 24) | 8.5 Days | Standard Deviation 7.4 |
| Control | Mean Days of Hospitalization From Baseline to End of Study (Month 24) | 16.2 Days | Standard Deviation 19.3 |
Secondary
Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24)
Time frame: Month 12 to end of study (Month 24)
Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus + CNI Reduction | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Total discontinued due to AE(s) | 8 Participants |
| Everolimus + CNI Reduction | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Pulmonary embolism | 2 Participants |
| Everolimus + CNI Reduction | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Skin problems | 1 Participants |
| Everolimus + CNI Reduction | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Hypercholesterolemia | 1 Participants |
| Everolimus + CNI Reduction | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Stroke | 1 Participants |
| Everolimus + CNI Reduction | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Muscular pain | 1 Participants |
| Everolimus + CNI Reduction | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Diarrhea | 1 Participants |
| Everolimus + CNI Reduction | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Edema | 1 Participants |
| Control | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Edema | 0 Participants |
| Control | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Total discontinued due to AE(s) | 0 Participants |
| Control | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Stroke | 0 Participants |
| Control | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Pulmonary embolism | 0 Participants |
| Control | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Diarrhea | 0 Participants |
| Control | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Skin problems | 0 Participants |
| Control | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Muscular pain | 0 Participants |
| Control | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) | Hypercholesterolemia | 0 Participants |
Secondary
Number of Patients in Need of Dialysis From Month 12 to End of Study (Month 24)
Time frame: Month 12 to end of study (Month 24)
Population: The intent-to-treat (ITT) population consisted of all patients as randomized, who were given at least one dose of study drug and had at least one post-baseline assessment. (Extension study)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus + CNI Reduction | Number of Patients in Need of Dialysis From Month 12 to End of Study (Month 24) | 0 Participants |
| Control | Number of Patients in Need of Dialysis From Month 12 to End of Study (Month 24) | 2 Participants |
Secondary
Number of Patients Who Died and Number of Patients With Graft Loss From Month 12 to End of Study (Month 24)
Number of patients not alive and number of patients with loss of their graft.
Time frame: Month 12 to end of study (Month 24)
Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus + CNI Reduction | Number of Patients Who Died and Number of Patients With Graft Loss From Month 12 to End of Study (Month 24) | Death | 3 Participants |
| Everolimus + CNI Reduction | Number of Patients Who Died and Number of Patients With Graft Loss From Month 12 to End of Study (Month 24) | Graft Loss | 0 Participants |
| Control | Number of Patients Who Died and Number of Patients With Graft Loss From Month 12 to End of Study (Month 24) | Death | 0 Participants |
| Control | Number of Patients Who Died and Number of Patients With Graft Loss From Month 12 to End of Study (Month 24) | Graft Loss | 0 Participants |
Secondary
Number of Patients With Biopsy-proven Acute Rejection From Month 12 to End of Study (Month 24)
Biopsy-proved acute rejection was defined as a treated acute rejection confirmed by biopsy, graded locally according to the International Society for Heart & Lung Transplantation (ISHLT) criteria. A treated acute rejection was defined as an acute rejection clinically suspected, whether biopsy-proven or not, which had been treated and confirmed by the investigator according to the response to therapy.
Time frame: Month 12 to end of study (Month 24)
Population: Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus + CNI Reduction | Number of Patients With Biopsy-proven Acute Rejection From Month 12 to End of Study (Month 24) | 6 Participants |
| Control | Number of Patients With Biopsy-proven Acute Rejection From Month 12 to End of Study (Month 24) | 5 Participants |