SCHEDULE Follow Up Visit 5-7 yr

Heart Transplantation Clinical Trial

— CRAD001ANO05  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02864706
• Other study ID #: CRAD001ANO05
• Secondary ID: CRAD001ANO026YFU
• Status: Completed
• Phase: Phase 4
• Start date: January 18, 2016
• Est. completion date: September 25, 2017

Study information

• Verified date: October 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: September 25, 2017
• Est. primary completion date: September 25, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Transplantation

Intervention

Drug:
• Everolimus
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.
• Cyclosporine
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)
• Mycophenolate mofetil
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
• Corticosteroids
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.

Locations

Country	Name	City	State
Denmark	Novartis Investigative Site	Århus N
Denmark	Novartis Investigative Site	Copenhagen
Norway	Novartis Investigative Site	Oslo
Sweden	Novartis Investigative Site	Göteborg
Sweden	Novartis Investigative Site	Linkoping
Sweden	Novartis Investigative Site	Lund

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Denmark,  Norway,  Sweden, 

References & Publications (1)

Andreassen AK, Andersson B, Gustafsson F, Eiskjaer H, Rådegran G, Gude E, Jansson K, Solbu D, Karason K, Arora S, Dellgren G, Gullestad L; SCHEDULE investigators. Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study. Am J Transplant. 2016 Apr;16(4):1238-47. doi: 10.1111/ajt.13588. Epub 2016 Jan 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Myocardial Structure and Function	Myocardial structure and function by echocardiography assessment measured by ventricular end systolic diameter.	within 5-7 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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