Tolvaptan add-on Therapy to Overcome Loop Diuretic Resistance in Acute Heart Failure With Renal Dysfunction (DR-AHF)

Gia Dinh People Hospital

Status: Unknown

Conditions: Acute Heart Failure

Treatments: Drug: Tolvaptan 15 MG

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04331132

92/CN-HĐĐĐ

Details and patient eligibility

About

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.

Full 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.

Enrollment: 128 estimated patients

Sex: All

Ages: 20 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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128 participants in 2 patient groups, including a placebo group

Conventional diuretic group

Placebo Comparator group

Description:

The conventional furosemide treatment will follow the modified 2019 Position Statement from the ESC Heart Failure Association

Treatment:

Drug: Tolvaptan 15 MG

Vasopressin-2 antagonist group

Active Comparator group

Description:

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

Treatment:

Drug: Tolvaptan 15 MG