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

NCT01966601 | Completed Phase 2 DMC

• 1 other identifier: CP027.2002
• Study Type: interventional
• Target: 620
• Locations: 12 countries
• Sites: 62

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).

Conditions

Acute Decompensated Heart Failure

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (4)

TRV027 dose #1

EXPERIMENTAL

TRV027 dose #1 via continuous IV infusion

Drug: TRV027 Dose #1

TRV027 dose #2

EXPERIMENTAL

TRV027 dose #2 via continuous IV infusion

Drug: TRV027 Dose #2

TRV027 dose #3

EXPERIMENTAL

TRV027 dose #3 via continuous IV infusion

Drug: TRV027 Dose #3

Placebo

PLACEBO COMPARATOR

Placebo via continuous IV infusion

Drug: Placebo

Interventions

TRV027 Dose #1 DRUG

TRV027 continuous intravenous infusion Dose #1

Also known as: Formerly known as TRV120027

TRV027 dose #1

TRV027 Dose #2 DRUG

TRV027 continuous intravenous infusion Dose #2

Also known as: Formerly known as TRV120027

TRV027 dose #2

TRV027 Dose #3 DRUG

TRV027 continuous intravenous infusion Dose #3

Also known as: Formerly known as TRV120027

TRV027 dose #3

Placebo DRUG

Placebo continuous intravenous infusion

Placebo

Eligibility Criteria

• Age: 21 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Trevena Inc.: lead

Study Sites (62)

Wayne State University

Detroit, Michigan, 48202, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

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Tennessee Center for Clinical Trials

Tullahoma, Tennessee, 37388, United States

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Michael E Debakey VA Medical Center

Houston, Texas, 77030, United States

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Buenos Aires, Argentina

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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

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Quilmes, Argentina

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Rosario, Argentina

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San Martín, Argentina

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San Miguel de Tucumán, Argentina

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Santa Fe, Argentina

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Dimitrovgrad, Bulgaria

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Kazanlak, Bulgaria

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Pazardzhik, Bulgaria

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Pleven, Bulgaria

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Smolyan, Bulgaria

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Sofia, Bulgaria

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Sofia, Bulgaria

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Edmonton, Alberta, Canada

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Ottawa, Ontario, Canada

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Brno, Czechia

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Hradec Králové, Czechia

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Olomouc, Czechia

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Prague, Czechia

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Berlin, Germany

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Dortmund, Germany

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Greifswald, Germany

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Budapest, Hungary

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Kaposvár, Hungary

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Pécs, Hungary

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Afula, Israel

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Ashkelon, Israel

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Hadera, Israel

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Haifa, Israel

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Jerusalem, Israel

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Nahariya, Israel

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Nazareth, Israel

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Safed, Israel

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Bad Nauheim, Poland

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Bialystok, Poland

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Grodzisk Mazowiecki, Poland

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Krakow, Poland

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Kłodzko, Poland

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Lublin, Poland

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Ruda Śląska, Poland

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Warsaw, Poland

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Wroclaw, Poland

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Baia Mare, Romania

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Bucharest, Romania

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Cluj-Napoca, Romania

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Craiova, Romania

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Târgu Mureş, Romania

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Moscow, Russia

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Saint Petersburg, Russia

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Saratov, Russia

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Bratislava, Slovakia

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Kocise, Slovakia

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Martin, Slovakia

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MeSH Terms

Interventions

Sar-Arg-Val-Tyr-Ile-His-Pro-Ala-OH

Study Officials

• David Soergel, MD

  Trevena Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2013
• First Posted: October 21, 2013
• Study Start: December 1, 2013
• Primary Completion: March 1, 2016
• Study Completion: September 1, 2016
• Last Updated: July 26, 2018

Record last verified: 2018-07

Locations

RU (3); IL (8); SL (3); PL (9); DE (3); US (4); CZ (4); AR (11); RO (5); BU (7); CA (2); HU (3)