Early Sequential Nephron Blockade in Acute Heart Failure Patients: A Randomised, Controlled Study (NEB-HF)

Chiang Mai University

Status and phase: Unknown; Phase 3

Conditions: Acute Kidney Injury; Acute Heart Failure

Treatments: Drug: Spironolactone or hydrochlorothiazide; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04465123

MED-2563-07080 (2)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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100 participants in 2 patient groups

Furosemide with spironolactone or hydrochlorothiazide

Experimental group

Description:

IV furosemide dosage will be adjusted according to the protocol as follows. Level 1: previous oral furosemide dose ≤80 mg/day; furosemide 80 mg IV bolus every 6 hours Level 2: previous oral furosemide dose 81-160 mg/day; furosemide 160 mg IV bolus every 6 hours Level 3: previous oral furosemide dose \>160 mg/day; furosemide 250 mg IV bolus every 6 hours Furosemide dosage will be adjusted to keep urine output between 3,000 and 5,000 ml/day and \>600 ml during 6 hours after furosemide administration. If the urine output \<3,000 ml/day or \<600 ml per 6 hours, furosemide dosage will be increase 1-level up per protocol above. If the urine output \>5,000 ml/day, furosemide dosage will be reduced 1-level down per protocol above. Patients will be received spironolactone or hydrochlorothiazide in combination with intravenous furosemide according to patients' serum potassium levels.

Treatment:

Drug: Spironolactone or hydrochlorothiazide

Furosemide with placebo

Active Comparator group

Description:

IV furosemide dosage will be adjusted according to the pre-defined protocol as shown in the experimental group. Patients will be received spironolactone placebo or hydrochlorothiazide placebo in combination with intravenous furosemide according to patients' serum potassium levels.

Treatment:

Drug: Placebo