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

Phase 2

Completed

• Conditions: Acute Decompensated Heart Failure
• Interventions: Drug: TRV027 Dose #1; Drug: TRV027 Dose #2; Drug: TRV027 Dose #3; Drug: Placebo

• Registration Number: NCT01966601
• Lead Sponsor: Trevena Inc.

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-09-02
• Study First Submitted QC: 2013-10-16
• Study First Posted: 2013-10-21
• Study Start: 2013-12
• Primary Completion: 2016-03
• Study Completion: 2016-09
• Status Verified: 2018-07
• Disposition First Submitted: 2018-07-23
• Disposition First Submitted QC: 2018-07-23
• Last Update Submitted: 2018-07-23
• Disposition First Posted: 2018-07-26
• Last Update Posted: 2018-07-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 620

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TRV027 dose #1	TRV027 Dose #1	TRV027 dose #1 via continuous IV infusion
TRV027 dose #2	TRV027 Dose #2	TRV027 dose #2 via continuous IV infusion
TRV027 dose #3	TRV027 Dose #3	TRV027 dose #3 via continuous IV infusion
Placebo	Placebo	Placebo via continuous IV infusion

Primary Outcome Measures

Name	Time	Method
composite z score	30 days	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.

Trial Locations

Locations (6)

Tennessee Center for Clinical Trials; 🇺🇸 Tullahoma, Tennessee, United States

Wayne State University; 🇺🇸 Detroit, Michigan, United States

Research Site; 🇸🇰 Martin, Slovakia

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Research Sites; 🇧🇬 Sofia, Bulgaria

Michael E Debakey VA Medical Center; 🇺🇸 Houston, Texas, United States