Nordic Everolimus (Certican) Trial in Heart and Lung Transplantation
- Conditions
- Disorder Related to Cardiac Transplantation
- Interventions
- Drug: Mycophenolic acid (MPA)/azathioprine (AZA)Drug: Calcineurin inhibitors (CNI)Drug: Steroids
- Registration Number
- NCT00377962
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 282
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Everolimus + CNI reduction Calcineurin inhibitors (CNI) 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. Control Mycophenolic acid (MPA)/azathioprine (AZA) 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. Control Calcineurin inhibitors (CNI) 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. Everolimus + CNI reduction Steroids 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. Control Steroids 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. Everolimus + CNI reduction Everolimus 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
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.
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 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.
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 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.
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.
Number of Patients in Need of Dialysis From Month 12 to End of Study (Month 24) Month 12 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)
Trial Locations
- Locations (1)
Novartis Investigative Site
🇸🇪Lund, Sweden