A Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Explore the Efficacy of TRV027 in Patients Hospitalized for Acute Decompensated Heart Failure
- Conditions
- Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]Heart Failure
- Registration Number
- EUCTR2013-002893-35-SK
- Lead Sponsor
- Trevena Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 500
Patients may be included in the study if all of the following criteria are met:
1.Men or women aged =21 years and = 85 years
a.Women of non-child-bearing potential must have:
i.Documentation of surgical sterilization (hysterectomy and/or bilateral oophorectomy) OR
ii.Experienced menopause: no menses for >12 months
b.Women of child bearing potential must have a:
i.A negative pregnancy test, AND
ii.Have had their most recent menstrual period = 2 weeks prior to presentation
2.Able to provide written informed consent
3.Pre-existing diagnosis of heart failure (treated by stable, heart failure therapy consistent with American College of Cardiology/American Heart Association and European Society of Cardiology practice guidelines for the treatment of chronic heart failure for at least 30 days prior to screening including any of the following classes of medications: diuretics, ACE inhibitors, beta-adrenergic blockers)
4.Systolic blood pressure =120 mmHg and = 200 mmHg within 30 minutes of randomization
5.Ventricular rate =125 bpm. Patients with rate-controlled persistent or permanent atrial fibrillation (aFib) at screening are permitted.
6. 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
AND at least two (2) of the following:
•Congestion on chest radiograph (CXR)
•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)
7.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
8.Patient report of dyspnea at rest or upon minimal exertion during screening at least one hour after administration of IV loop diuretic.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 125
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 375
Patients will be excluded if any of the following apply:
1.Women who are pregnant or breast-feeding
2.Clinical presentation:
a.Suspected acute coronary syndrome (ACS) based on clinical judgment or coronary revascularization in the 3 months prior to screening or planned during current admission. NOTE: the presence of elevated troponin concentrations in the absence of other clinical findings, is not sufficient for a diagnosis of ACS
b.Temperature >38.5oC (oral or equivalent) or suspected sepsis or active infection requiring IV antimicrobial treatment
c.Clinically significant anemia (hematocrit < 25%)
d.Current or planned ultrafiltration, paracentesis, hemofiltration or dialysis at time of screening
e.Any mechanical ventilation requiring tracheal intubation and sedation at the time of screening or during the during current hospitalization
f.CPAP/BiPAP discontinued less than 1 hour prior to randomization, unless prescribed for treatment of sleep apnea and used for >3 months
g.History of primary pulmonary hypertension
h.History or current use of left ventricular assist devices (LVADs) or intra-aortic balloon pumps (IABPs)
i.Administration of intravenous radiographic contrast agent within 72 hours prior to screening or presence of acute contrast induced nephropathy at the time of screening
j.Presence of clinically significant arrhythmia that, in the Investigator’s opinion, is the primary cause of worsening heart failure symptoms, including ventricular tachycardia or bradyarrhythmia with ventricular rate <45 bpm
3.Medications:
a.Use of intravenous nitroprusside or nesiritide within 2 hours prior to randomization
b.Intravenous nitrates (nitroglycerin at a dose > 0.1 mg/kg/hr or equivalent) or any IV nitrates if the patient’s screening systolic blood pressure is < 150 mmHg within 1 hour prior to randomization
c.Use for at least 4 hours or planned use of inotropes (milrinone, levosimendan, dobutamine, or >2.5 mcg/kg/min dopamine), within 48 hours prior to randomization or any use of IV inotropes or vasopressors within 2 hours prior to randomization
d.Use of angiotensin receptor blocking drugs (ARBs) within 7 days of prior to randomization. Angiotensin converting enzyme (ACE) inhibitors are permitted.
e.Use of any investigational medication within 30 days or 5 terminal elimination half-lives (whichever is longer) prior to randomization
f.As determined by the Investigator, clinically significant hypersensitivity or allergy to, or intolerance of, angiotensin receptor blockers
4.Medical history:
a.Major surgery within 8 weeks prior to screening
b.Stroke within 3 months prior to screening
c.eGFR (sMDRD) <20 mL/min/1.73m2 or >75 mL/min/1.73m2 between presentation and randomization
d.Post cardiac or renal transplant
e.Listed for renal transplant or cardiac transplant with anticipated transplant time to transplant < 6 months
f.History of severe left ventricular outlet obstruction (either valvular or sub-valvular), severe mitral valve stenosis or severe aortic regurgitation
g.Any cardiac valvular abnormality that requires surgical correction
h.Complex congenital heart disease
i.Diagnosis of hypertrophic or restrictive cardiomyopathy
j.In the opinion of the Investigator, significant pulmonary or hepatic disease that could interfere with the evaluation of safety or efficacy of TRV027
k.In the opinion of the Investigator has a life expectancy of less than 6 months
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method