Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure

• Status: Terminated
• Trial end date: 2014-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is a multi-center, prospective, randomized, double blind, placebo-controlled clinical trial. Subjects in the study will be adults with New York Heart Association (NYHA) Class II-IV heart failure (HF) due to left ventricular systolic dysfunction (LVSD), left ventricular ejection fraction (LVEF) <0.40, and secondary pulmonary hypertension (PH). The purpose of the study is to evaluate the safety, effectiveness, and effects of tadalafil compared to placebo on the subjects' functional capacity / quality of life.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: HealthCore-NERI; New England Research Institutes
• Collaborators: Massachusetts General Hospital; National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Tadalafil

Criteria

Inclusion Criteria:

• Male or female age 21 years or older.

• NYHA Class II-IV HF with LVSD (most recent LVEF < 0.40).

• At high risk of future clinical instability, indicated by EITHER:

a hospitalization for the primary reason of decompensated HF within the 12 months prior to screening; OR a plasma B-type Natriuretic Peptide (BNP) level ≥ 300 pg/ml or N-terminal prohormone of brain natriuretic peptide (NT-proBNP) ≥1800pg/ml measured during a period of clinical stability in the 3 months prior to screening.

• Documented secondary PH within the last 6 months

• Medication and device treatment according to current American Heart Association/American College of Cardiology (AHA/ACC) guidelines.

• Stable medical therapy for 30 days prior to randomization

• African-American patients intolerant of or otherwise unable or unwilling to utilize isosorbide dinitrate/hydralazine therapy will be included.

• Willingness to comply with protocol, attend follow-up appointments, complete all study assessments and provide written informed consent.

Exclusion Criteria:

• Concurrent or anticipated nitrate use for any reason, or nitrate use within the 14 days prior to screening through the day of randomization.

• Known allergy, hypersensitivity (anaphylaxis), or adverse reaction to tadalafil or other Phosphodiesterase Type 5 (PDE5) inhibitor

• Erectile dysfunction treated with a PDE5 inhibitor.

• Severe renal dysfunction defined as an estimated glomerular filtration rate (GFR) < 30 ml/min/1.73 m^2 or requiring chronic dialysis

• Current use of alpha antagonists (except carvedilol or tamsulosin) or use of cytochrome P450 3A4 inhibitors (ketoconazole, itraconazole, erythromycin, or cimetidine). Patients who have used a protease inhibitor that is a P450 3A4 inhibitor for longer than one week can be enrolled.

• Pulmonary arterial hypertension (World Health Organization (WHO) Group I, III-V) for which PDE5 inhibitor therapy may be indicated

• Severe pulmonary disease requiring home oxygen therapy

• Comorbidities including clinically significant valvular stenosis (aortic valve area < 0.8 cm^2 or a mitral valve area <1.0 cm^2), uncontrolled hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg) or hypotension (systolic blood pressure <85 mmHg)

• Chronic intravenous inotrope therapy

• Non-arteritic anterior ischemic optic neuropathy (NAION)

• ST elevation MI (STEMI) within 90 days prior to screening

• Coronary Artery Bypass Grafting (CABG) or mitral valve surgery, initiation of cardiac resynchronization (CRT) or initiation of β-blocker therapy within the 6 months prior to screening

• Infiltrative or inflammatory myocardial disease (e.g. amyloid, sarcoid)

• Heart transplant recipient

• United Network Organ Sharing (UNOS) status 1A or 1B

• Mechanical circulatory support (MCS) use or planned MCS use at time of consent

• Active malignancy (except non-melanoma skin cancer) requiring therapy other than observation.

• Severe non-cardiac illness resulting in life expectancy judged less than three years

• Known chronic hepatic disease defined as aspartate aminotransferase (AST) and alanine transaminase (ALT) levels > 3.0 times the upper limit of normal

• Inability to walk even a few steps due to non-cardiac (e.g. orthopedic) reasons

• Participation in any clinical trial within the last 30 days (with exception of observational study)

• Previous randomization in PITCH-HF