A Study to Explore the Efficacy of TRV027 in Patients Hospitalized for Acute Decompensated Heart Failure (BLAST-AHF)
Primary Purpose
Acute Decompensated Heart Failure
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TRV027 Dose #1
TRV027 Dose #2
TRV027 Dose #3
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Acute Decompensated Heart Failure
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
- 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
Sites / Locations
- Wayne State University
- University of Cincinnati
- Tennessee Center for Clinical Trials
- Michael E Debakey VA Medical Center
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
TRV027 dose #1
TRV027 dose #2
TRV027 dose #3
Placebo
Arm Description
TRV027 dose #1 via continuous IV infusion
TRV027 dose #2 via continuous IV infusion
TRV027 dose #3 via continuous IV infusion
Placebo via continuous IV infusion
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01966601
Brief Title
A Study to Explore the Efficacy of TRV027 in Patients Hospitalized for Acute Decompensated Heart Failure
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
December 2013 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
September 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Trevena Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Decompensated Heart Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
620 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TRV027 dose #1
Arm Type
Experimental
Arm Description
TRV027 dose #1 via continuous IV infusion
Arm Title
TRV027 dose #2
Arm Type
Experimental
Arm Description
TRV027 dose #2 via continuous IV infusion
Arm Title
TRV027 dose #3
Arm Type
Experimental
Arm Description
TRV027 dose #3 via continuous IV infusion
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo via continuous IV infusion
Intervention Type
Drug
Intervention Name(s)
TRV027 Dose #1
Other Intervention Name(s)
Formerly known as TRV120027
Intervention Description
TRV027 continuous intravenous infusion Dose #1
Intervention Type
Drug
Intervention Name(s)
TRV027 Dose #2
Other Intervention Name(s)
Formerly known as TRV120027
Intervention Description
TRV027 continuous intravenous infusion Dose #2
Intervention Type
Drug
Intervention Name(s)
TRV027 Dose #3
Other Intervention Name(s)
Formerly known as TRV120027
Intervention Description
TRV027 continuous intravenous infusion Dose #3
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo continuous intravenous infusion
Primary Outcome Measure Information:
Title
composite z score
Description
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.
Time Frame
30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Soergel, MD
Organizational Affiliation
Trevena Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Tennessee Center for Clinical Trials
City
Tullahoma
State/Province
Tennessee
ZIP/Postal Code
37388
Country
United States
Facility Name
Michael E Debakey VA Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
Ciudad Autónoma de Buenos Aires
Country
Argentina
Facility Name
Research Site
City
Ciudad De Cordoba
Country
Argentina
Facility Name
Research Site
City
Cordoba
Country
Argentina
Facility Name
Research Site
City
Coronel Suarez
Country
Argentina
Facility Name
Research Site
City
Corrientes
Country
Argentina
Facility Name
Research Site
City
La Plata
Country
Argentina
Facility Name
Research Site
City
Moron
Country
Argentina
Facility Name
Research Site
City
Quilmes
Country
Argentina
Facility Name
Research Site
City
Rosario
Country
Argentina
Facility Name
Research Site
City
San Martin
Country
Argentina
Facility Name
Research Site
City
San Miguel de Tucumán
Country
Argentina
Facility Name
Research Site
City
Santa Fe
Country
Argentina
Facility Name
Research Site
City
Dimitrovgrad
Country
Bulgaria
Facility Name
Research Site
City
Kazanlak
Country
Bulgaria
Facility Name
Research Site
City
Pazardzhik
Country
Bulgaria
Facility Name
Research Site
City
Pleven
Country
Bulgaria
Facility Name
Research Site
City
Smolyan
Country
Bulgaria
Facility Name
Research Sites
City
Sofia
Country
Bulgaria
Facility Name
Research Site
City
Sofia
Country
Bulgaria
Facility Name
Research Site
City
Edmonton
State/Province
Alberta
Country
Canada
Facility Name
Research Site
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
Research Site
City
Brno
Country
Czechia
Facility Name
Research Site
City
Hradec Kralove
Country
Czechia
Facility Name
Research Site
City
Olomouc
Country
Czechia
Facility Name
Research Site
City
Prague
Country
Czechia
Facility Name
Research Site
City
Praha
Country
Czechia
Facility Name
Research Site
City
Berlin
Country
Germany
Facility Name
Research Site
City
Dortmund
Country
Germany
Facility Name
Research Site
City
Greifswald
Country
Germany
Facility Name
Research Site
City
Budapest
Country
Hungary
Facility Name
Research Site
City
Kaposvar
Country
Hungary
Facility Name
Research Site
City
Pecs
Country
Hungary
Facility Name
Research Site
City
Afula
Country
Israel
Facility Name
Research Site
City
Ashkelon
Country
Israel
Facility Name
Research Site
City
Hadera
Country
Israel
Facility Name
Research Site
City
Haifa
Country
Israel
Facility Name
Research Site
City
Jerusalem
Country
Israel
Facility Name
Research Site
City
Nahariya
Country
Israel
Facility Name
Research Site
City
Nazareth
Country
Israel
Facility Name
Research Site
City
Safed
Country
Israel
Facility Name
Research Site
City
Bad Nauheim
Country
Poland
Facility Name
Research Site
City
Bialystok
Country
Poland
Facility Name
Research Site
City
Grodzisk Mazowiecki
Country
Poland
Facility Name
Research Site
City
Klodzko
Country
Poland
Facility Name
Research Site
City
Kraków
Country
Poland
Facility Name
Research Site
City
Lublin
Country
Poland
Facility Name
Research Site
City
Ruda Slaska
Country
Poland
Facility Name
Research Site
City
Warszawa
Country
Poland
Facility Name
Research Site
City
Wroclaw
Country
Poland
Facility Name
Research Site
City
Baia Mare
Country
Romania
Facility Name
Research Site
City
Bucharest
Country
Romania
Facility Name
Research Site
City
Cluj-Napoca
Country
Romania
Facility Name
Research Site
City
Craiova
Country
Romania
Facility Name
Research Site
City
Targu Mures
Country
Romania
Facility Name
Research Site
City
Moscow
Country
Russian Federation
Facility Name
Research Site
City
Saint Petersburg
Country
Russian Federation
Facility Name
Research Site
City
Saratov
Country
Russian Federation
Facility Name
Research Site
City
Bratislava
Country
Slovakia
Facility Name
Research Site
City
Kocise
Country
Slovakia
Facility Name
Research Site
City
Martin
Country
Slovakia
12. IPD Sharing Statement
Learn more about this trial
A Study to Explore the Efficacy of TRV027 in Patients Hospitalized for Acute Decompensated Heart Failure
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