The trial had two coprimary end points. The primary efficacy end point was the patient's global assessment of symptoms, measured with the use of a visual-analogue scale and quantified as the area under the curve (AUC) of serial assessments from baseline to 72 hours (see Section 3 in the Supplementary Appendix for a description of the method used for quantification of the area under the curve).17 (link) For this assessment, patients were asked to evaluate their general well-being by marking a 10-cm vertical line, with the top labeled “best you have ever felt” and the bottom labeled “worst you have ever felt.” We scored the patients' markings on a scale of 0 to 100 by measuring the distance in millimeters from the bottom of the line. The primary safety end point was the change in the serum creatinine level from baseline to 72 hours. See Section 3 in the Supplementary Appendix for more detailed definitions of the study end points.
Prespecified secondary end points included the following: patient-reported dyspnea (as assessed with the use of a visual-analogue scale such as that described above and quantified as the AUC of serial assessments from baseline to 72 hours); changes in body weight and net fluid loss; the proportion of patients who were free from congestion (defined as jugular venous pressure of <8 cm, with no orthopnea and with trace peripheral edema or no edema) at 72 hours; worsening renal function (defined as an increase in the serum creatinine level of more than 0.3 mg per deciliter) at any time from randomization to 72 hours; worsening or persistent heart failure; treatment failure (see Section 3 in the Supplementary Appendix); changes in biomarker levels at 72 hours, day 7 or discharge, and day 60; and clinical end points, including the composite of death, rehospitalization, or an emergency room visit within 60 days, as well as the composite of total number of days hospitalized or dead during the 60 days after randomization.