Tolvaptan add-on Therapy to Overcome Loop Diuretic Resistance in Acute Heart Failure With Renal Dysfunction
- Registration Number
- NCT04331132
- Lead Sponsor
- Gia Dinh People Hospital
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 128
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vasopressin-2 antagonist group Tolvaptan 15 MG Tolvaptan 15mg once daily for 2 days will be added-on the furosemide strategy based on the modified 2019 Position Statement from the ESC Heart Failure Association Conventional diuretic group Tolvaptan 15 MG The conventional furosemide treatment will follow the modified 2019 Position Statement from the ESC Heart Failure Association
- Primary Outcome Measures
Name Time Method Cumulative urine volume output at 48h after randomization Hour 48 Urine volume in mL
- Secondary Outcome Measures
Name Time Method 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
Cumulative dose of furosemide at 48h after randomization Hour 48 Furosemide dose in mg
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)
Changes in NT-proBNP at 48h after randomization Hour 0, Hour 48 Changes in NT-proBNP (pg/mL)
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
Trial Locations
- Locations (1)
Cardiology Department
🇻🇳Ho Chi Minh City, Vietnam