Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure (PITCH-HF)

This study has been terminated.
(terminated by funding agency)
Sponsor:
Collaborators:
Massachusetts General Hospital
Information provided by (Responsible Party):
New England Research Institutes
ClinicalTrials.gov Identifier:
NCT01910389
First received: July 25, 2013
Last updated: February 19, 2014
Last verified: January 2014

July 25, 2013
February 19, 2014
November 2013
February 2014   (final data collection date for primary outcome measure)
Time to either cardiovascular (CV) mortality or HF hospitalization [ Time Frame: Through each subject's last semi-annual visit, up to a maximum of 3 years per subject ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01910389 on ClinicalTrials.gov Archive Site
  • Time to CV mortality [ Time Frame: Through each subject's last semi-annual visit, up to a maximum of 3 years per subject ] [ Designated as safety issue: No ]
  • Time to HF hospitalization [ Time Frame: Through each subject's last semi-annual visit, up to a maximum of 3 years per subject ] [ Designated as safety issue: No ]
  • Time to all-cause mortality [ Time Frame: Through each subject's last semi-annual visit, up to a maximum of 3 years per subject ] [ Designated as safety issue: No ]
  • Time to all-cause mortality or CV hospitalization (myocardial infarction, acute coronary syndrome, stroke, arrhythmia, or heart failure) [ Time Frame: Through each subject's last semi-annual visit, up to a maximum of 3 years per subject ] [ Designated as safety issue: No ]
  • Frequency of CV hospitalizations [ Time Frame: Through each subject's last semi-annual visit, up to a maximum of 3 years per subject ] [ Designated as safety issue: No ]
  • Frequency of HF hospitalizations [ Time Frame: Through each subject's last semi-annual visit, up to a maximum of 3 years per subject ] [ Designated as safety issue: No ]
  • Change in 6 minute walk distance from baseline to 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Change in MLHFQ score from baseline to 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Change in 6 minute walk distance from baseline to 18 months [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Trend in 6 minute walk distance from baseline through 18 months [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score from baseline to 18 months [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Trend in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score from baseline through 18 months [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure
Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Heart Failure
  • Pulmonary Hypertension
  • Drug: Tadalafil
    Other Name: Adcirca
  • Drug: Placebo for tadalafil
  • Active Comparator: Tadalafil
    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.
    Intervention: Drug: Tadalafil
  • Placebo Comparator: Placebo
    Placebo of tadalafil. Subjects will take one tablet once per day and will be titrated to two tablets once per day after one week. Subjects are on study drug for the duration of the trial.
    Intervention: Drug: Placebo for tadalafil
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
23
February 2014
February 2014   (final data collection date for primary outcome measure)

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
Both
21 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01910389
U01HL105463
Yes
New England Research Institutes
New England Research Institutes
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Massachusetts General Hospital
Principal Investigator: Marc J. Semigran, MD Massachusetts General Hospital
Principal Investigator: Susan F Assmann, PhD New England Research Institutes, Inc.
Principal Investigator: Flora S Siami, MPH New England Research Institutes, Inc.
New England Research Institutes
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP