Clinical trial NCT01966601: A Study to Explore the Efficacy of TRV027 in Patients Hospitalized for Acute Decompensated Heart Failure
Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Explore the Efficacy of TRV027 in Patients Hospitalized for Acute Decompensated Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Decompensated Heart Failure
Lead sponsor: Trevena Inc.
Sponsor class: INDUSTRY
First posted: 2013-10-21
Enrollment: 620
Sex: ALL
Minimum age (years): 21
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

1. Men or women aged ≥21 years and ≤ 85 years 1a.Women of non-child-bearing potential
2. Able to provide written informed consent
3. Pre-existing diagnosis of heart failure and at least 30 days treatment with daily oral loop diuretics
4. Systolic blood pressure ≥105 mmHg and ≤ 160 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
     * 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)
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

Exclusion Criteria:

1. Women who are pregnant or breast-feeding
2. Clinical presentation:

   1. Suspected ACS based on clinical judgment
   2. Coronary revascularization in the 3 months prior to screening or planned during current admission.
   3. Temperature \>38.5oC
   4. Clinically significant anemia
   5. Serum sodium \>145 mEq/L (145 mmol/L)
   6. Current or planned ultrafiltration, paracentesis, hemofiltration or dialysis at time of screening
   7. Any mechanical ventilation
   8. CPAP/BiPAP discontinued less than 1 hour prior to randomization
   9. History of LVAD or IABP within the last year
   10. Intravenous radiographic contrast agent within 72 hours prior to screening or presence of acute contrast induced nephropathy at the time of screening
   11. Presence of clinically significant arrhythmia
   12. Uncertainty of ability to complete follow up
3. Medications:

   1. nitroprusside or nesiritide
   2. Intravenous nitrates
   3. use of inotropes
   4. Use of ARBs within 7 days of prior to randomization
   5. Use of any investigational medication within 30 days
   6. clinically significant hypersensitivity or allergy to, or intolerance of, angiotensin receptor blockers
4. Medical history:

   1. Major surgery within 8 weeks prior to screening
   2. Stroke within 3 months prior to screening
   3. eGFR (sMDRD) \<20 mL/min/1.73m2 or \>75 mL/min/1.73m2 between presentation and randomization
   4. Post cardiac or renal transplant
   5. Listed for renal transplant or cardiac transplant with anticipated transplant time to transplant \< 6 months
   6. History of severe left ventricular outlet obstruction (either valvular or sub-valvular), severe mitral valve stenosis or severe aortic regurgitation
   7. Cardiac valvular abnormality that requires surgical correction
   8. Complex congenital heart disease
   9. Hypertrophic or restrictive cardiomyopathy
   10. significant pulmonary or hepatic disease that could interfere with the evaluation of safety or efficacy of TRV027
   11. life expectancy of less than 6 months

Primary outcomes:
measure: composite z score
timeFrame: 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Tullahoma
country: United States
facility: Tennessee Center for Clinical Trials
state: Tennessee
city: Houston
country: United States
facility: Michael E Debakey VA Medical Center
state: Texas
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad De Cordoba
country: Argentina
facility: Research Site
city: Cordoba
country: Argentina
facility: Research Site
city: Coronel Suarez
country: Argentina
facility: Research Site
city: Corrientes
country: Argentina
facility: Research Site
city: La Plata
country: Argentina
facility: Research Site
city: Moron
country: Argentina
facility: Research Site
city: Quilmes
country: Argentina
facility: Research Site
city: Rosario
country: Argentina
facility: Research Site
city: San Martin
country: Argentina
facility: Research Site
city: San Miguel de Tucumán
country: Argentina
facility: Research Site
city: Santa Fe
country: Argentina
facility: Research Site
city: Dimitrovgrad
country: Bulgaria
facility: Research Site
city: Kazanlak
country: Bulgaria
facility: Research Site
city: Pazardzhik
country: Bulgaria
facility: Research Site
city: Pleven
country: Bulgaria
facility: Research Site
city: Smolyan
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Sites
city: Sofia
country: Bulgaria
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Brno
country: Czechia
facility: Research Site
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Prague
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dortmund
country: Germany
facility: Research Site
city: Greifswald
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Kaposvar
country: Hungary
facility: Research Site
city: Pecs
country: Hungary
facility: Research Site
city: Afula
country: Israel
facility: Research Site
city: Ashkelon
country: Israel
facility: Research Site
city: Hadera
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Nahariya
country: Israel
facility: Research Site
city: Nazareth
country: Israel
facility: Research Site
city: Safed
country: Israel
facility: Research Site
city: Bad Nauheim
country: Poland
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Grodzisk Mazowiecki
country: Poland
facility: Research Site
city: Klodzko
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Ruda Slaska
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Baia Mare
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Craiova
country: Romania
facility: Research Site
city: Targu Mures
country: Romania
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saratov
country: Russian Federation
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Kocise
country: Slovakia
facility: Research Site
city: Martin
country: Slovakia
facility: Research Site
Study officials:
affiliation: Trevena Inc.
name: David Soergel, MD
role: STUDY_DIRECTOR
References: