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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
  Purpose

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.


Condition Intervention Phase
Heart Failure
Pulmonary Hypertension
Drug: Tadalafil
Drug: Placebo for tadalafil
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure

Resource links provided by NLM:


Further study details as provided by New England Research Institutes:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 23
Study Start Date: November 2013
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Tadalafil
Other Name: Adcirca
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.
Drug: Placebo for tadalafil

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01910389

  Show 63 Study Locations
Sponsors and Collaborators
New England Research Institutes
Massachusetts General Hospital
Investigators
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.
  More Information

No publications provided

Responsible Party: New England Research Institutes
ClinicalTrials.gov Identifier: NCT01910389     History of Changes
Other Study ID Numbers: U01HL105463
Study First Received: July 25, 2013
Last Updated: February 19, 2014
Health Authority: United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Keywords provided by New England Research Institutes:
Heart failure
Pulmonary hypertension
tadalafil
Phosphodiesterase Type 5 Inhibition

Additional relevant MeSH terms:
Heart Failure
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Heart Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Tadalafil
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Therapeutic Uses
Urological Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on November 27, 2014