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.
Age range
18 Years
Sex
ALL
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Change from baseline to day 7 of plasma volume by add-on to loop diuretic therapy
Timeframe: 7 days
Change from baseline to 6 weeks of plasma volume by add-on to loop diuretic therapy
Timeframe: 6 weeks
Natriuretic effect of adjuvant to loop diuretic therapy
Timeframe: 1 day