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

Request for individual participant data (IPD) has to be submitted to the Institutional Review Board (IRB) of Faculty of Medicine, Chiang Mai University, Chiang Mai, THAILAND.