SCHEDULE Follow Up Visit 5-7 yr

Study Overview
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Brief Summary
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The major aim of this extension study was to evaluate the long-term effect (i.e. 5 to 7 years) of early initiation of everolimus and early elimination of CsA compared to standard immunosuppressive regimen including CsA on primary and secondary endpoints investigated in the SCHEDULE (NCT01266148) main study.

Detailed Description
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This protocol was written to describe the procedures for a single 5, 6 or 7 year follow-up control visit of patients who participated in the 12-month SCHEDULE (NCT01266148) study and the following 3-year follow-up examination/visit. The aim of this 5 to 7-year follow-up visit was to examine the effect of long term treatment, i.e. 5, 6 or 7 years, with early initiation of everolimus (Certican®) and early elimination of cyclosporine (CsA), compared to standard immunosuppressive regimen including CsA, on renal and heart function. During the time period of this follow-up examinations, this visit was performed as part of a routine annual visit 5, 6 or 7 years since transplantation (and inclusion in the original SCHEDULE study). Study code of SCHEDULE, the core study: CRAD001ANO02 (EudraCT No.: 2009-013074-41)

Official Title
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5, 6 or 7 Year Follow-up Control After the SCHEDULE Study (SCANDINAVIAN HEART TRANSPLANT EVEROLIMUS DE NOVO STUDY WITH EARLY CNI AVOIDANCE)

Conditions
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Heart Transplantation

Intervention / Treatment
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* Drug: Everolimus
* Drug: Cyclosporine
* Drug: Mycophenolate mofetil
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who participated in the SCHEDULE 12-month main study, and who completed the 3 year follow-up visit Patients who are coming for a regular annual clinic visit 5 to 7 years after randomization in the main study Obtaining of a separate signed patient informed consent will be required for participation in this follow-up examination. Exclusion Criteria: Patients with a retransplanted heart since the original SCHEDULE study
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EVEROLIMUS<br>patients received everolimus (Certican), low-exposure CsA (Neoral), mycophenolate mofetil (MMF) and corticosteroids with CsA withdrawal after 7-11 weeks | Drug: Everolimus<br>* All patients, independent of their initial randomization in the core study, were followed up as in one single group Commercially available everolimus (Certican®), oral route, was used.<br>|
| Active Comparator: Control<br>patients received standard CsA, MMF and corticosteroids | Drug: Cyclosporine<br>* Cyclosporine (CsA) control group target blood level: 150-350 ng/mL (month 1-3); 100-250 ng/mL (month 4-6); 60-200 ng/mL (month 7-12); everolimus group target blood level: 75-175 ng/mL (month 1-3)<br>Drug: Mycophenolate mofetil<br>* Mycophenolate mofetil (MMF) target dose for control group: 2000-3000 mg/day everolimus group target dose: 1500-2000 mg/day and 75-175 ng/mL after week 11<br>Drug: Corticosteroids<br>* Corticosteroids (CS) initiated at 0.2-0.5 mg/kg/day. Tapered to no less than 0.1 mg/kg at Month 3 for control and everolimus groups.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measured Glomerular Filtration Rate (mGFR) | Renal function as assessed by measured Glomerular Filtration Rate (mGFR) (Cr-EDTA or iohexol clearance). Baseline Visit 1 and Patient 4252 excluded from the intent treat analysis set. | at the 5-7 year follow-up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of Cardiac Allograft Vasculopathy (CAV) Recorded by Intravascular Ultrasound (IVUS) | Cardiac Allograft Vasculopathy (CAV) was defined as mean maximal intimal thickness (MIT) ≥0.5 mm, measured for the entire matched pullback recording by intravascular ultrasound (IVUS). The incidence of CAV at 5-7 years was compared between groups using the Cochran-Mantel-Haenszel test with stratification according to baseline distribution of CAV incidence. | within 5-7 years | 
| Percent of Participants With Incidence of Coronary Allograft Vasculopathy (CAV) | Cardiac Allograft Vasculopathy (CAV) was defined as mean maximal intimal thickness (MIT) ≥0.5 mm, measured for the entire matched pullback recording by intravascular ultrasound (IVUS). The incidence of CAV at 5-7 years was compared between groups using the Cochran-Mantel-Haenszel test with stratification according to baseline distribution of CAV incidence. | at the 5-7 year follow-up | 
| Myocardial Structure and Function | Myocardial structure and function by echocardiography assessment measured by ventricular end systolic diameter. | within 5-7 years | 
| Quality of Life by SF-36 Change From Pre-transplantation to 5-7 Year Follow-up | This Quality of life Short Form Survey with 36 items (Minnesota Living with Heart Failure Questionnaire)was administered to patients pre-transplantation and after transplantation at the 5-7 year visit. This data represents the change. The survey consist of scores on a scale. Each form is scaled from 0 t 100. 0 = maximum disability and 100 equals no disability. | at the 5-7 year visit | 
| Change From Baseline in the Euro Quality of Life 5D | Change from baseline in Euro Quality of Life-5D from 3 Year Follow-Up to 5 to 7 Year Follow-Up Baseline Visit 1 (ITT Set) Euro Quality of Life 5D (EQ-5D): is a descriptive system of healthrelated quality of life states consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) each of which can be assessed as one of three levels of severity (no problems/some or moderate problems/extreme problems). A Visual Analogue Scale (VAS)-scale is also included in the EQ-5D questionnaire. The EQ-5D index is calculated based on the United Kingdom Time Trade-Off (TTO) N3 value set which converts the five dimensions scores into a single measure with a possible range from -0.163 (worst possible health state) to +1 (perfect health). A positive change from baseline indicates an improvement in Quality of Life. | Baseline, 5-7 year visit | 
| Change From Baseline in Visual Analog Scale (VAS) | Change in visual analog scale (VAS) from baseline to the 5 to 7 Year follow up visit. 0 is no pain; and 10 is the worst possible pain | baseline, at the 5-7 year visit | 
| Number of Participants With Beck Depression Inventory (BDI) | Beck Depression Inventory (BDI) Score has the following categories of depression. Normal, Mild, Moderate Severe and Missing. | at the 5-7 year visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allograft rejection, xenograft rejection, host vs graft disease, transplant