A Study to Explore the Efficacy of TRV027 in Patients Hospitalized for Acute Decompensated Heart Failure

Acute Decompensated Heart Failure Clinical Trial

— BLAST-AHF  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01966601
• Other study ID #: CP027.2002
• Status: Completed
• Phase: Phase 2
• Start date: December 2013
• Est. completion date: September 2016

Study information

• Verified date: July 2018
• Source: Trevena Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 620
• Est. completion date: September 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Decompensated Heart Failure
• Heart Failure

Intervention

Drug:
• TRV027 Dose #1
TRV027 continuous intravenous infusion Dose #1
• TRV027 Dose #2
TRV027 continuous intravenous infusion Dose #2
• TRV027 Dose #3
TRV027 continuous intravenous infusion Dose #3
• Placebo
Placebo continuous intravenous infusion

Locations

Country	Name	City	State
Argentina	Research Site	Ciudad Autónoma de Buenos Aires
Argentina	Research Site	Ciudad De Cordoba
Argentina	Research Site	Cordoba
Argentina	Research Site	Coronel Suarez
Argentina	Research Site	Corrientes
Argentina	Research Site	La Plata
Argentina	Research Site	Moron
Argentina	Research Site	Quilmes
Argentina	Research Site	Rosario
Argentina	Research Site	San Martin
Argentina	Research Site	San Miguel de Tucumán
Argentina	Research Site	Santa Fe
Bulgaria	Research Site	Dimitrovgrad
Bulgaria	Research Site	Kazanlak
Bulgaria	Research Site	Pazardzhik
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Smolyan
Bulgaria	Research Site	Sofia
Bulgaria	Research Sites	Sofia
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Ottawa	Ontario
Czechia	Research Site	Brno
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Olomouc
Czechia	Research Site	Prague
Czechia	Research Site	Praha
Germany	Research Site	Berlin
Germany	Research Site	Dortmund
Germany	Research Site	Greifswald
Hungary	Research Site	Budapest
Hungary	Research Site	Kaposvar
Hungary	Research Site	Pecs
Israel	Research Site	Afula
Israel	Research Site	Ashkelon
Israel	Research Site	Hadera
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Nahariya
Israel	Research Site	Nazareth
Israel	Research Site	Safed
Poland	Research Site	Bad Nauheim
Poland	Research Site	Bialystok
Poland	Research Site	Grodzisk Mazowiecki
Poland	Research Site	Klodzko
Poland	Research Site	Kraków
Poland	Research Site	Lublin
Poland	Research Site	Ruda Slaska
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Romania	Research Site	Baia Mare
Romania	Research Site	Bucharest
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Craiova
Romania	Research Site	Targu Mures
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saratov
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Kocise
Slovakia	Research Site	Martin
United States	University of Cincinnati	Cincinnati	Ohio
United States	Wayne State University	Detroit	Michigan
United States	Michael E Debakey VA Medical Center	Houston	Texas
United States	Tennessee Center for Clinical Trials	Tullahoma	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Trevena Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Canada,  Czechia,  Germany,  Hungary,  Israel,  Poland,  Romania,  Russian Federation,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	composite z score	The primary clinical endpoint is a of the following outcomes: (1) time from randomization to death through day 30, (2) time from randomization to heart failure re-hospitalization through day 30, (3) time from randomization to worsening heart failure through day 5, (4) change in dyspnea VAS score (calculated area under the curve) from baseline through day 5, and (5) length of initial hospital stay (in days) from randomization. The component outcomes will be combined by deriving an average Z for each patient.	30 days