Cholesterol Lowering With EVOLocumab to Prevent Cardiac Allograft Vasculopathy in De-novo Heart Transplant Recipients
Condition: Cardiac Allograft Vasculopathy
MeSH terms: Vascular Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      The main goal of this study is to evaluate the effect of the proprotein convertase
      subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab on cardiac allograft vasculopathy in de
      novo heart transplant recipients.

      Secondary objectives are to assess the impact of treatment on: i) cholesterol levels, ii)
      renal function, iii) inflammation, iv) quality of life, v) cardiac function as assessed by
      biomarkers and echocardiography, vi) the number of rejections, and (vii) safety and
      tolerability. As an exploratory outcome, the investigators will asses the effect of treatment
      on clinical events (death, myocardial infarction, cerebral stroke, cancer, end stage renal
      disease).
    

Detailed description: 
      Cardiac allograft vasculopathy is an important cause of morbidity and mortality in heart
      transplant recipients. Previous data show that, although clinical coronary artery disease
      often manifests years after heart transplantation, there are substantial changes in the
      coronary artery intima thickness over the first year after transplantation, suggesting that
      the adverse process starts shortly after transplantation. Moreover, the investigator's
      previous data have suggested that, whereas early intervention can prevent the long-term
      progression of cardiac allograft vasculopathy, the same intervention is less effective when
      administered late after heart transplantation. Thus, there seems to be a window of
      opportunity for preventive measures against cardiac allograft vasculopathy in de-novo
      transplant recipients.

      The strong association between cholesterol levels and coronary heart disease in the general
      population, the high cholesterol levels in heart transplant recipients, the high prevalence
      of vasculopathy in the cardiac allograft, and the association between cholesterol levels and
      cardiac allograft vasculopathy together provide a strong rationale for aggressive cholesterol
      lowering in heart transplant recipients. Statins improve outcomes in heart transplant
      recipients, but their limited effect on post-transplant cholesterol levels, adverse effects,
      and drug interactions contribute to their not providing sufficient prophylaxis against
      post-transplant atherosclerotic disease.

      Evolocumab is a well-tested drug with a favourable safety profile. It effectively reduces
      cholesterol levels on top of statin therapy in patients with coronary heart disease. The
      investigators hypothesise that evolocumab on top of statin therapy will significantly lower
      low density lipoprotein (LDL) levels in de novo heart transplant recipients. The
      investigators assume that this reduction in cholesterol levels will manifest as a reduced
      burden of cardiac allograft vasculopathy as measured by intracoronary ultrasound. Ultimately,
      the investigators believe that a reduced burden of vasculopathy will translate to reduced
      morbidity and long-term mortality in heart transplant recipients. The EVOLVD trial is a
      randomised, placebo-controlled, double-blind study designed to test the hypothesis that
      treatment with evolocumab can ameliorate cardiac allograft vasculopathy in heart transplant
      recipients.
    

Intervention name(s): Evolocumab; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 420 mg evolocumab will be administered subcutaneously by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector.; Placebo will be administered subcutaneously by giving 3 injections consecutively within 30 minutes using the single-use prefilled autoinjector.
Other intervention name(s): Repatha
Intervention MeSH terms: Evolocumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Evolocumab; Heart Transplantation; Vasculopathy