SCHEDULE - Scandinavian Heart Transplant Everolimus de Novo Study With Early Calcineurin Inhibitor (CNI) Avoidance

Phase 4

Completed

Conditions: Renal Function and Chronic Allograft Vasculopathy

Interventions: Drug: Cyclosporine
Drug: Mycophenolate mofetil
Drug: Corticosteroids
Drug: Everolimus
Drug: Anti Thymocyte Globulin

Registration Number: NCT01266148

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: A controlled, randomized, open-label, multicenter study evaluating if early initiation of everolimus and early elimination of cyclosporine in de novo heart transplant recipients can improve long-term renal function and slow down the progression of chronic allograft vasculopathy

Detailed Description: This was a prospective, multi-center, randomized, controlled, parallel group, open label study in de novo heart transplant recipients. Patients eligibility for randomization was assessed 5 days after heart transplant.. Patients fulfilling the inclusion and exclusion criteria were randomized to one of two treatment groups: either conventional treatment with Cyclosporine A (CsA), Mycophenolate mofetil (MMF), and corticosteroids (Group A), or low-dose CsA and everolimus, reduced dose MMF, and corticosteroids (Group B). After 7 to 11 weeks, CsA was discontinued in Group B, while the standard triple-drug immunosuppressive regimen was maintained in Group A.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 115

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Everolimus	Anti Thymocyte Globulin	Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.
Control	Mycophenolate mofetil	Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Everolimus	Cyclosporine	Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.
Everolimus	Corticosteroids	Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.
Everolimus	Everolimus	Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.
Control	Corticosteroids	Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Control	Anti Thymocyte Globulin	Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Everolimus	Mycophenolate mofetil	Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.
Control	Cyclosporine	Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.

Primary Outcome Measures

Name	Time	Method
Measured Glomerular Filtration Rate (mGFR), 12 Months After Heart Transplantation	Week 52	Measured Glomerular Filtration Rate (mGFR) describes the flow rate of filtered fluid through the kidney. GFR is equal to the clearance rate when any solute is freely filtered and is neither reabsorbed nor secreted by the kidneys. The rate therefore measured is the quantity of the substance in the urine that originated from a calculable volume of blood. Participants' urine was used for this assessment at week 52 after heart transplant.

Secondary Outcome Measures

Name	Time	Method
Average Level of Protenuria at Week 52	52 weeks	Proteinuria is measured as the ratio of albumin/creatinine mg/mmol. Measurements were taken from participants urine samples.
Lipid Profile at 12 Months	52 weeks	Total Cholesterol, LDL-Chol, HDL-Chol and TG at week 52. Measurements were taken via participants blood samples.
Progression of Chronic Allograft Vasculopathy (CAV) Based on Maximal Intimal Thickness (MIT) From Baseline to Week 52	Baseline and week 52	The progression of chronic allograft vasculopathy (CAV) was assessed by intravascular ultrasound (IVUS) examinations and measured Maximal Intimal Thickness (MIT)(in mm). A major coronary epicardial artery (preferentially the left-anterior descending coronary artery) was imaged, and the MIT parameters were recorded at baseline and at week 52.
Progression of Chronic Allograft Vasculopathy (CAV) Based on Incidence of Chronic Allograft Vasculopathy (CAV) From Baseline to Week 52	Baseline and week 52	the progression of chronic allograft vasculopathy (CAV) assessed by intravascular ultrasound (IVUS) examinations, measured the incidence of CAV (in percent of patients) at baseline and at week 52. Incidence of CAV represents percent of patients having a MIT (maximal intima thickness) \> 0.5 mm.
Change in Calculated Glomerular Filtration Rate From Pre-transplantation to Week 52	Day 1, weeks 7 to 11(baseline) and of week 52	Change in calculated glomerular filtration rate from pre-transplantation to week 52 was calculated according to the Modification of Diet in Renal Disease (MDRD) method. Measurements were taken prior to transplant (day 1), between weeks 7 to 11 and end week 52.
Occurrence of Treatment Failures up to 12 Months After Transplant	52 weeks	Treatment failure was defined as the number of participants who died or lost their graft at any timepoint througout the duration of the study.
Calculated Glomerular Filtration Rate From Pre-Transplantation to Week 52	Day 1, weeks 7 to 11 and of week 52	Calculated Glomerular Filtration Rate from pre-transplantation to week 52 was calculated according to the Modification of Diet in Renal Disease (MDRD) method. Measurements were taken prior to transplant (day 1), between weeks 7 to 11 and end of week 52.
Number of Rejections Leading to Hemodynamic Compromise	52 weeks	Number of all rejections were recorded through the duration of the study with the intent to identify rejections leading to hemodynamic compromise.
Change in Quality of Life Assessed by SF-36 (Minnesota Living With Heart Failure Questionnaire ([MLHF)]) From Pre-transplant to Week 52 of Treatment	Pre transplant and 52 weeks	Change in Quality of Life was assessed via the SF-36 (Minnesota Living with Heart Failure questionnaire (\[MLHF)\]) before transplant surgery and at week 52 of treatment. The SF-36 is a validated, self-administered questionnaire. The questionnaire, which includes 36 questions measures 8 dimensions of health: physical function, role-physical, bodily pain, general health, vitality, social function, role-emotional, and mental health. Scores can be summarized in 2 summary components assessing physical and mental health. Items in each dimension are coded, aggregated, summed, and transformed into a scale ranging from 0 (worse health) to 100 (best health).
Change in Quality of Life - Euro Quality of Life 5D (EQ-5D)	Pre transplant and 52 weeks	Change in Quality of Life was assessed via the EQ-5D questionnaire which consists of: EQ-5D-5L descriptive system and EQ Visual Analogue scale (EQ VAS). The EQ-5D-5L comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems). The patient indicates his/her health state by checking the most appropriate statement. This decision results in a 1-digit number expressing the level selected for that dimension. The digits for 5 dimensions are combined in a 5-digit number describing the respondent's health state. The possible score is 1 to 5 where a lower number indicates improvement. The EQ VAS records the patient's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine'. The score is 0 to 100 where a higher score represents improvement.