Acute Heart Failure
Conditions
Keywords
acute heart failure, worsening renal function, loop diuretic resistance, vasopressin-2 receptor antagonist
Brief summary
Renal dysfunction, which comprises 10%-40% of acute heart failure patients (AHF), plays an important role in diuretic resistance mechanism. DR-AHF was designed to demonstrate the effectiveness of early tolvaptan (a vasopressin-2 receptor antagonist) add-on therapy in acute heart failure patients with renal dysfunction and clinical evidence of loop diuretic resistance.
Detailed description
This is a single-center, open-label, randomized controlled trial, which will enroll 128 patients hospitalized due to AHF. These patients with wet-warm phenotype whose estimated glomerular filtration rates at admission are above 15 and below 60 mL/min/1.73 m2, and cumulative urine output \<300 mL in 2 hours after the first dose of intravenous furosemide will be randomly assigned 1:1 to receive a standard care with uptitrating intravenous furosemide alone or a combination therapy with tolvaptan 15mg once daily for 2 days. The standard furosemide treatment will follow the modified 2019 Position Statement from the ESC Heart Failure Association. The primary endpoint is the cumulative urine output at 48 hour. Key secondary endpoints include the improvement of fractional excretion of sodium at 6 hour, the total dose of furosemide, the changes in the body weights, the net fluid loss, the lessening of diastolic dysfunction parameters on echocardiography, and the incidence of clinically relevant worsening renal function at 48 hour.
Interventions
DRUGTolvaptan 15 MG
vasopressin-2 receptor antagonist 15mg once daily is added-on to the conventional diuretic strategy
Sponsors
Otsuka Pharmaceutical Vietnam
Gia Dinh People Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Acute heart failure patients with wet-warm phenotype whose estimated glomerular filtration rates at admission are above 15 and below 60 mL/min/1.73 m2, and cumulative urine output \<300 mL in 2 hours after the first dose of intravenous furosemide will be randomly assigned 1:1 to receive a standard care with uptitrating intravenous furosemide alone or a combination therapy with tolvaptan 15mg once daily for 2 days
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Admitted to hospital with a primary diagnosis of acute heart failure with wet-warm phenotype * Cumulative urine volume output \< 300ml within 2 hours after the first dose of intravenous furosemide * eGFR at admission 15-60ml/min/1.73m2
Exclusion criteria
* Acute coronary syndrome * Anuria * Sepsis * Consciousness impairment * Pregnant or breastfeeding women * Severe valvular heart diseases (severe valvular stenosis or regurgitation) * Admission sodium level \> 140 mEq/L * Serum total bilirubin \> 3 mg/dL * Serum potassium \> 5.5 mmol/L * Allergy or contraindication for tolvaptan * Emergency indication for hemodialysis * Cardiogenic shock or mechanical circulation support
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative urine volume output at 48h after randomization | Hour 48 | Urine volume in mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptom of dyspnea by 7-point Likert scale at 24h and 48h after randomization | Hour 24, Hour 48 | 3: markedly better, 2: moderately better, 1: minimally better, 0: no change, -1: minimally worse, -2: moderately worse, -3: markedly worse |
| Changes in body weight at 24h and 48h after randomization | Hour 24, Hour 48 | weight in gram |
| Incidence of clinically relevant worsening renal function at 24h and 48h after randomization | Hour 24, Hour 48 | An increase in serum creatinine ≥ 0.3 mg/dL within 48 hours accompanying doubling the dose of furosemide according to the diuretic treatment protocol |
| Changes in serum electrolytes measured at 12h, 24h and 48h after randomization | Hour 12, Hour 24, Hour 48 | Changes in serum sodium (mmol/L), potassium (mmol/L), chloride (mmol/L) |
| Changes in urine electrolyte excretion at 6h, 24h and 48h | Hour 6, Hour 24, Hour 48 | Increase in sodium (mmol/L), potassium (mmol/L) and chloride (mmol/L) excretion adjusted for urine creatinine (umol/L) |
| Cumulative dose of furosemide at 48h after randomization | Hour 48 | Furosemide dose in mg |
| Changes in mitral e' on echocardiography | Hour 24, Hour 48 | Average of septal e' (cm/s) and lateral e' (cm/s) on tissue doppler imaging in apical 4-chamber view |
| Changes in E/e' ratio on echocardiography | Hour 24, Hour 48 | The ratio between mitral E (cm/s) and average e' (cm/s) |
| Changes in left atrial volume on echocardiography | Hour 24, Hour 48 | Average of left atrial volumes (ml) by Simpson's rule in apical 4-chamber and 2-chamber view |
| Changes in tricuspid regurgitation maximal velocity on echocardiography | Hour 24, Hour 48 | Tricuspid regurgitation maximal velocity (m/s) by continuous wave doppler in apical 4-chamber view |
| Changes in inferior vena cava maximal diameter on echocardiography | Hour 24, Hour 48 | Inferior vena cava maximal diameter (mm) in subcostal view |
| Changes in NT-proBNP at 48h after randomization | Hour 0, Hour 48 | Changes in NT-proBNP (pg/mL) |
Countries
Vietnam
Contacts
Primary ContactNhat M. Giang, M.D
Backup ContactHai H. Nguyen, Ph.D
Outcome results
None listed