To evaluate the overall safety and efficacy of TRV027 when administered in addition to standard of care (SOC) on mortality, morbidity, dyspnea, and length of stay in patients hospitalized with Acute Decompensated Heart Failure (ADHF).

Elegibilidad

Edad mínima: 21 YearsEdad máxima: 85 YearsSexo: ALL

Criterios de inclusión

Men or women aged ≥21 years and ≤ 85 years 1a.Women of non-child-bearing potential
Able to provide written informed consent
Pre-existing diagnosis of heart failure and at least 30 days treatment with daily oral loop diuretics
Systolic blood pressure ≥105 mmHg and ≤ 160 mmHg within 30 minutes of randomization
Ventricular rate ≤125 bpm. Patients with rate-controlled persistent or permanent atrial fibrillation (aFib) at screening are permitted.
Presence of ADHF defined by:
BNP \> 400 pg/mL or NT-proBNP \> 1600 pg/mL
For patients with BMI \>30 kg/m2: BNP \> 200 pg/mL or NT-proBNP \> 800 pg/mL
For patients with rate-controlled persistent or permanent aFib: BNP \> 600 pg/mL or NT-proBNP \> 2400 pg/mL
Congestion on chest radiograph (CXR)
AND at least two (2) of the following:
Rales by chest auscultation
Edema ≥ +1 on a 0-3 + scale, indicating indentation of skin with mild digital pressure that requires 10 or more seconds to resolve in any dependent area including extremities or sacral region.
Elevated jugular venous pressure (≥8 cm H2O)
Receipt of a IV loop diuretic at a minimum dose 40 mg furosemide (or equivalent loop diuretic) for the treatment of dyspnea due to ADHF at least 1 hour prior to anticipated randomization and the initiation of study medication
Patient report of dyspnea at rest or upon minimal exertion during screening at least one hour after administration of IV loop diuretic

Criterios de exclusión

Post cardiac or renal transplant
Listed for renal transplant or cardiac transplant with anticipated transplant time to transplant \< 6 months
History of severe left ventricular outlet obstruction (either valvular or sub-valvular), severe mitral valve stenosis or severe aortic regurgitation
Women who are pregnant or breast-feeding
Clinical presentation:
Suspected ACS based on clinical judgment
Coronary revascularization in the 3 months prior to screening or planned during current admission.
Temperature \>38.5oC
Clinically significant anemia
Serum sodium \>145 mEq/L (145 mmol/L)
Current or planned ultrafiltration, paracentesis, hemofiltration or dialysis at time of screening
Any mechanical ventilation
CPAP/BiPAP discontinued less than 1 hour prior to randomization
History of LVAD or IABP within the last year
Intravenous radiographic contrast agent within 72 hours prior to screening or presence of acute contrast induced nephropathy at the time of screening
Presence of clinically significant arrhythmia
Uncertainty of ability to complete follow up
Medications:
nitroprusside or nesiritide
Intravenous nitrates
use of inotropes
Use of ARBs within 7 days of prior to randomization
Use of any investigational medication within 30 days
clinically significant hypersensitivity or allergy to, or intolerance of, angiotensin receptor blockers
Medical history:
Major surgery within 8 weeks prior to screening
Stroke within 3 months prior to screening
eGFR (sMDRD) \<20 mL/min/1.73m2 or \>75 mL/min/1.73m2 between presentation and randomization
Cardiac valvular abnormality that requires surgical correction
Complex congenital heart disease
Hypertrophic or restrictive cardiomyopathy
significant pulmonary or hepatic disease that could interfere with the evaluation of safety or efficacy of TRV027
life expectancy of less than 6 months

Ubicaciones

Research Site

Buenos Aires, Argentina

Research Site

Coronel Suárez, Argentina

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Corrientes, Argentina

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Córdoba, Argentina

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La Plata, Argentina

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Morón, Argentina

Research Site

Quilmes, Argentina

Research Site

Rosario, Argentina

Research Site

San Martín, Argentina

Research Site

San Miguel de Tucumán, Argentina

Research Site

Santa Fe, Argentina

A Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Explore the Efficacy of TRV027 in Patients Hospitalized for Acute Decompensated Heart Failure

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

TRV027 Dose #1

TRV027 Dose #2

TRV027 Dose #3

Placebo

Ubicaciones

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Patrocinadores