Clinical trial NCT04465123: Early Sequential Nephron Blockade in Acute Heart Failure Patients: A Randomised, Controlled Study
Official title: Furosemide With Early Sequential Nephron Blockade Versus Furosemide Alone in Acute Heart Failure Patients With Furosemide-guided Diuretic Resistance: A Double-blinded, Randomized, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Acute Heart Failure
Acute Kidney Injury
Keywords: Acute heart failure
Diuretic resistance
Sequential nephron blockade
Diuretic combination
Lead sponsor: Chiang Mai University
Sponsor class: OTHER
First posted: 2020-07-09
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Urine volume
timeFrame: 72 hours
Secondary outcomes:
measure: Urine volume
timeFrame: 24 and 48 hours
measure: Body weight
timeFrame: 72 hours after randomisation
measure: Length of hospital admission
timeFrame: During hospital admission period
measure: Furosemide dose
timeFrame: 72 hours after randomisation
measure: Levels of B-type atrial natriuretic peptide (BNP)
timeFrame: 72 hours and 7 days after randomisation
measure: Number of participants with adverse events
timeFrame: During hospital admission
measure: Dyspnea score assessed by visual analogue scale
timeFrame: At randomization, and 6, 12, 24, 48 and 72 hours after randomization
Other outcomes:
Locations:
city: Chiang Mai
country: Thailand
facility: Chiang Mai University Hospital, Faculty of Medicine, Chiang Mai University
Study officials:
affiliation: Instructor, Division of Nephrology, Department of Internal Medicine
name: Kajohnsak Noppakun, MD
role: PRINCIPAL_INVESTIGATOR
References: