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| Name | Class |
|---|---|
| Otsuka Pharmaceutical Vietnam | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Conventional diuretic group | Placebo Comparator | The conventional furosemide treatment will follow the modified 2019 Position Statement from the ESC Heart Failure Association |
|
| Vasopressin-2 antagonist group | Active Comparator | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tolvaptan 15 MG | Drug | vasopressin-2 receptor antagonist 15mg once daily is added-on to the conventional diuretic strategy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative urine volume output at 48h after randomization | Urine volume in mL | Hour 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative dose of furosemide at 48h after randomization | Furosemide dose in mg | Hour 48 |
| Symptom of dyspnea by 7-point Likert scale at 24h and 48h after randomization | 3: markedly better, 2: moderately better, 1: minimally better, 0: no change, -1: minimally worse, -2: moderately worse, -3: markedly worse |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Nhat M. Giang, M.D | Contact | +84919963999 | minhnhat_210189@yahoo.com | |
| Hai H. Nguyen, Ph.D | Contact | +84908247359 | bsnguyenhoanghai@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Hai H. Nguyen, Ph.D | Cardiology Department | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cardiology Department | Recruiting | Ho Chi Minh City | 70000 | Vietnam |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27206819 | Background | Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016 Jul 14;37(27):2129-2200. doi: 10.1093/eurheartj/ehw128. Epub 2016 May 20. No abstract available. | |
| 32164892 |
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| ID | Term |
|---|---|
| D000077602 | Tolvaptan |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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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
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|
| Hour 24, Hour 48 |
| Changes in body weight at 24h and 48h after randomization | weight in gram | Hour 24, Hour 48 |
| Incidence of clinically relevant worsening renal function at 24h and 48h after randomization | An increase in serum creatinine ≥ 0.3 mg/dL within 48 hours accompanying doubling the dose of furosemide according to the diuretic treatment protocol | Hour 24, Hour 48 |
| Changes in serum electrolytes measured at 12h, 24h and 48h after randomization | Changes in serum sodium (mmol/L), potassium (mmol/L), chloride (mmol/L) | Hour 12, Hour 24, Hour 48 |
| Changes in urine electrolyte excretion at 6h, 24h and 48h | Increase in sodium (mmol/L), potassium (mmol/L) and chloride (mmol/L) excretion adjusted for urine creatinine (umol/L) | Hour 6, Hour 24, Hour 48 |
| Changes in NT-proBNP at 48h after randomization | Changes in NT-proBNP (pg/mL) | Hour 0, Hour 48 |
| Changes in mitral e' on echocardiography | Average of septal e' (cm/s) and lateral e' (cm/s) on tissue doppler imaging in apical 4-chamber view | Hour 24, Hour 48 |
| Changes in E/e' ratio on echocardiography | The ratio between mitral E (cm/s) and average e' (cm/s) | Hour 24, Hour 48 |
| Changes in left atrial volume on echocardiography | Average of left atrial volumes (ml) by Simpson's rule in apical 4-chamber and 2-chamber view | Hour 24, Hour 48 |
| Changes in tricuspid regurgitation maximal velocity on echocardiography | Tricuspid regurgitation maximal velocity (m/s) by continuous wave doppler in apical 4-chamber view | Hour 24, Hour 48 |
| Changes in inferior vena cava maximal diameter on echocardiography | Inferior vena cava maximal diameter (mm) in subcostal view | Hour 24, Hour 48 |
| Background |
| Felker GM, Ellison DH, Mullens W, Cox ZL, Testani JM. Diuretic Therapy for Patients With Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Mar 17;75(10):1178-1195. doi: 10.1016/j.jacc.2019.12.059. |
| 30600580 | Background | Mullens W, Damman K, Harjola VP, Mebazaa A, Brunner-La Rocca HP, Martens P, Testani JM, Tang WHW, Orso F, Rossignol P, Metra M, Filippatos G, Seferovic PM, Ruschitzka F, Coats AJ. The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019 Feb;21(2):137-155. doi: 10.1002/ejhf.1369. Epub 2019 Jan 1. |
| 35155599 | Derived | Minh NG, Hoang HN, Maeda D, Matsue Y. Tolvaptan Add-on Therapy to Overcome Loop Diuretic Resistance in Acute Heart Failure With Renal Dysfunction (DR-AHF): Design and Rationale. Front Cardiovasc Med. 2022 Jan 27;8:783181. doi: 10.3389/fcvm.2021.783181. eCollection 2021. |