The purpose of this study is to determine the effects on heart failure signs and symptoms of
the use of either ertugliflozin, metolazone or placebo, in conjunction with intravenous loop
diuretic use in acute settings and chronic oral loop diuretic therapy.
There are two general purposes for this study. The proposed study is both larger and more
rigorous than essentially all PK/PD studies that form the basis of current practice with loop
diuretics as well as all studies looking at add-on thiazide therapy (current
guideline-recommended adjuvant). The second is to generate a mechanistic understanding of the
pleotropic cardio-renal factors with chronic therapy that differentiate ertugliflozin from
traditional diuretics particularly in how they maintain reduced blood volume without the
complication of over-diuresis and volume depletion.