Paitents will be enrolled at least one year after heart transplant MedDRA version: 9.1 Level: SOC Classification code 10007541
Conditions
Interventions
Trade Name: CERTICAN
Pharmaceutical Form: Tablet
INN or Proposed INN: Everolimus
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 250-
Trade Name: CELLCEPT
Pharmace
Sponsors
AZIENDA OSPEDALIERA OSPEDALE NIGUARDA CA` GRANDA (A.O. DI RILIEVO NAZIONALE)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients eligible for inclusion have to fulfil all the following criteria: age >= 18 years at the time of enrolment; HTx at least 1 year before; be able and willing to give informed consent; baseline maintenance immunosuppression including CyA (for at least 1 month) at randomization; presence of one or more of the following conditions: 1) recurrent rejection within the first year (three or more treatments with additional steroids, either orally or intravenously, for acute rejection); 2) late (> 1 year after HTx) acute rejection treated with steroids; 3) cardiac allograft vasculopathy/chronic rejection, defined as follows: >50% stenosis of at least 1 vessel/branch, or diffuse disease, according to Gao criteria, and/or intimal thickness at IVUS >= 0.5 mm in at least 1 segment. Qualifying angiography/IVUS should be dated less than 1 year prior to randomization; 4) renal dysfunction, defined as GFR, calculated with MDRD formula, between 30 and 60 ml/min/1.73 square meters, or =/> 15% reduction of GFR within the last 12 months, confirmed by two or more measurements obtained at least two weeks apart Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - ongoing or planned pregnancy; - severe left ventricular dysfunction: ejection fraction = 800mg/day); - severe dyslipidemia: total cholesterol >350 mg/dl, triglycerides >750 mg/dl;- severe anemia: hemoglobin (Hb) < 10 g/dl; - platelet count < 100000/mm3; - white blood cell count <4000/mm3; - current cancer (with the exception of skin cancer); - history of prior cancer (except skin cancer) with a disease-free interval <3 years; - active hepatitis B or C (HBV-DNA positive, or HCV-RNA positive; or HBsAg positive or antiHCV positive associated with AST/ALT levels more than normal upper limit x 4); - need for oral anticoagulation; - known intolerance to any of the study drugs; - ongoing major infection (patient may be evaluated for enrolment after resolution); - ongoing acute rejection (patient may be evaluated for enrolment after resolution); - comorbidities that could independently reduce life expectancy. - baseline maintenance immunosuppression including Tacrolimus (pts may be evaluated at least 1 month after switching to CyA) - baseline maintenance immunosuppression including Everolimus or Sirolimus.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare the cumulative incidence of the primary outcome, that is a composite endpoint at three years defined as hierarchical occurrence of death, retransplantation, hospitalization for cardiovascular causes (i.e. resuscitated cardiac arrest, heart failure, acute coronary syndrome, revascularization procedures), reduction of ejection fraction of at least 10 points, progression of allograft vasculopathy detected with coronary angiography +/- intravascular ultrasound (IVUS), renal function worsening and cancer.;Secondary Objective: Secondary objectives of the study are to compare the experimental treatments with respect to: - Mortality at three years; deaths will be also divided into cardiovascular and non-cardiovascular deaths. - First occurrence of retransplantation at three years. - First occurrence of resuscitated cardiac arrest at three years. - First occurrence of hospitalization for heart failure at three years; total number of hospitalizations for heart failure at three years. - First occurrence of hospitalization for acute coronary syndrome; total number of hospitalizations for acute coronary syndrome at three years. - First occurrence of revascularization; total number of revascularization procedures at three years.- Proportion of patients (pts) showing a loss of ejection fraction >/= 10 points at three years; - Proportion of pts showing progression of allograft vasculopathy at three years;- Economic evaluation through a cost-benefit analysis.;Primary end point(s): The primary outcome of the study is a composite endpoint at three years, defined as hierarchical occurrence of death, retransplantation, hospitalization for cardiovascular causes (i.e. resuscitated cardiac arrest, heart failure, acute coronary syndrome, revascularization procedures), reduction of ejection fraction of at least 10 points, progression of allograft vasculopathy detected with coronary angiography +/- IVUS (as defin | — |
Countries
Italy
Outcome results
None listed