Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure

Brief Title

Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure

Official Title

Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure

Brief 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.
    


Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Composite Outcome of Cardiovascular (CV) Mortality or Heart Failure (HF) Hospitalization

Secondary Outcome

 Cardiovascular Mortality

Condition

Heart Failure

Intervention

Tadalafil

Study Arms / Comparison Groups

 Tadalafil
Description:  Tadalafil is supplied in 20 mg tablets. Subjects will take 20 mg (one tablet) once per day and will be titrated to 40 mg (two tablets once per day) after one week. Subjects are on study drug for the duration of the trial.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

23

Start Date

November 2013

Completion Date

February 2014

Primary Completion Date

February 2014

Eligibility 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
      

Gender

All

Ages

21 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Marc J. Semigran, MD, , 

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT01910389

Organization ID

U01HL105463


Responsible Party

Sponsor

Study Sponsor

HealthCore-NERI

Collaborators

 National Heart, Lung, and Blood Institute (NHLBI)

Study Sponsor

Marc J. Semigran, MD, Principal Investigator, Massachusetts General Hospital


Verification Date

January 2014