SCHEDULE Follow Up Visit 5-7 yr

Phase 4

Completed

Conditions: Heart Transplantation

Interventions: Drug: Everolimus
Drug: Cyclosporine
Drug: Mycophenolate mofetil
Drug: Corticosteroids

Registration Number: NCT02864706

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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: 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)

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 95

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Control	Corticosteroids	patients received standard CsA, MMF and corticosteroids
EVEROLIMUS	Everolimus	patients received everolimus (Certican), low-exposure CsA (Neoral), mycophenolate mofetil (MMF) and corticosteroids with CsA withdrawal after 7-11 weeks
Control	Cyclosporine	patients received standard CsA, MMF and corticosteroids
Control	Mycophenolate mofetil	patients received standard CsA, MMF and corticosteroids

Primary Outcome Measures

Name	Time	Method
Measured Glomerular Filtration Rate (mGFR)	at the 5-7 year follow-up visit	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.

Secondary Outcome Measures

Name	Time	Method
Percent of Participants With Incidence of Coronary Allograft Vasculopathy (CAV)	at the 5-7 year follow-up	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.
Change From Baseline in Visual Analog Scale (VAS)	baseline, at the 5-7 year visit	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
Number of Participants With Beck Depression Inventory (BDI)	at the 5-7 year visit	Beck Depression Inventory (BDI) Score has the following categories of depression. Normal, Mild, Moderate Severe and Missing.
Progression of Cardiac Allograft Vasculopathy (CAV) Recorded by Intravascular Ultrasound (IVUS)	within 5-7 years	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.
Myocardial Structure and Function	within 5-7 years	Myocardial structure and function by echocardiography assessment measured by ventricular end systolic diameter.
Quality of Life by SF-36 Change From Pre-transplantation to 5-7 Year Follow-up	at the 5-7 year visit	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.
Change From Baseline in the Euro Quality of Life 5D	Baseline, 5-7 year visit	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.