Early Sequential Nephron Blockade in Acute Heart Failure Patients: A Randomised, Controlled Study
Early Sequential Nephron Blockade in Acute Heart Failure Patients: A Randomised, Controlled Study
This study aims to demonstrate the efficacy of sequential nephron blockade by adding
 hydrochlorothiazide or spironolactone on intravenous furosemide compared to intravenous
 furosemide alone in the treatments of volume overload in patients with acute heart failure
 who have diuretic resistance from furosemide stress test.
This study is a randomised, double-blinded, double-dummy, placebo-controlled study to
 demonstrate the efficacy of oral hydrochlorothiazide or spironolactone in combination with
 intravenous furosemide compared to intravenous furosemide in combination with placebo. Dosage
 of intravenous furosemide will be adjusted according to pre-defined protocol. The primary
 outcome is urine volume during 72 hours after randomisation.
Inclusion Criteria:

 -  Age ≥18 years

 -  Diagnosis of acute heart failure which is defined by 2 of the 3 following features:
 ≥2+ leg edema, jugular venous pressure >10 cm from physical examination or central
 venous pressure >10 mmHg, and bilateral pulmonary edema or bilateral pleural effusion
 from chest radiography

 -  Patients consent to participate into the study

 Exclusion Criteria:

 -  Patients who receive furosemide ≥500 mg/day or hydrochlorothiazide ≥100 mg/day or
 spironolactone ≥100 mg/day or tolvaptan of any doses

 -  Patients who have systolic blood pressure <100 mmHg or who need vasoactive drugs
 inotropic agents (except dobutamine)

 -  Patients with intravascular volume depletion from clinical evaluation

 -  Patients with chronic kidney disease stage 5 (estimated glomerular filtration rate <15
 ml/min/1.73 m2) or patients who receive maintenance dialysis

 -  Patients who require renal replacement therapy at the time of admission

 -  Patients whom diagnosed hypertrophic obstructive cardiomyopathy, severe valvular
 stenosis or complex congenital heart disease

 -  Patients with sepsis or systemic infection

 -  Pregnant women

 -  Patients who have history of furosemide, spironolactone or hydrochlorothiazide allergy