Table 1 Objectives and endpoints in PRADA II

In patients with early breast cancer scheduled for anthracycline-containing anti-cancer therapy, to assess whether the administration of sacubitril/valsartan can prevent or is associated with attenuation of the reduction in left ventricular systolic function measured by CMR

Change in LVEF, as determined by CMR from randomization to end of blinded therapy (18 months)

Secondary

 To assess whether the administration of sacubitril/valsartan is associated with:

(1)

prevention of reduction in left ventricular systolic function measured by echocardiography or CMR

a. Change in LVEF, as determined by echocardiography from randomization to end of blinded therapy (18 months)

b. Change in GLS, as determined by echocardiography from randomization to end of blinded therapy (18 months)

c. Change in GLS, as determined by CMR from randomization to end of blinded therapy (18 months)

d. Change in end-systolic volume measured by CMR

(2)

reduced incidence of a significant reduction in left ventricular systolic function measured by CMR or echocardiography

Incidence of clinically significant reduction in left ventricular systolic function expressed as

a. An absolute reduction in LVEF ≥ 5% on CMR

or

b. A relative percentage reduction of GLS > 15%

(3)

reduced incidence of cardiotoxicity measured by CMR or echocardiography

Incidence of cardiotoxicity expressed as:

a. An absolute reduction in LVEF ≥ 10% to a value below 50% as measured by CMR or echocardiography

or

b. clinical heart failure

(4)

reduced early, acute and late, chronic cardiotoxic injury measured by cardiac biomarkers

Cardiotoxic injury expressed as change in circulating concentrations of hs-cTnI, hs-cTnT and NT-proBNP