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

  Hide Study Locations
Locations
United States, Alabama
Heart Center Inc - Research
Huntsville, Alabama, United States
United States, Arkansas
Baptist Health Transplant Institute
Little Rock, Arkansas, United States
United States, California
Allianz Medical and Research Center
Fountain Valley, California, United States
United States, Delaware
Christiana Care Health System
Newark, Delaware, United States
United States, Florida
Broward Health
Ft. Lauderdale, Florida, United States
Miller School of Medicine University of Miami
Miami, Florida, United States
Orlando Health
Orlando, Florida, United States
Charlotte Heart Group Research Center
Port Charlotte, Florida, United States
Brevard Cardiovascular Research Associates
Rockledge, Florida, United States
United States, Georgia
University Cardiology Associates LLC
Augusta, Georgia, United States
Eisenhower Army Medical Center
Fort Gordon, Georgia, United States
United States, Illinois
Northwestern University
Chicago, Illinois, United States
University of Illinois Hospital
Chicago, Illinois, United States
Methodist Medical Group Cardiology
Peoria, Illinois, United States
United States, Kentucky
Baptist Hospital East
Louisville, Kentucky, United States
Research Integrity LLC
Owensboro, Kentucky, United States
United States, Louisiana
LSU Health Sciences Center
New Orleans, Louisiana, United States
United States, Maine
Maine Research Associates
Auburn, Maine, United States
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States
United States, Massachusetts
Primary Care Cardiology Research, Inc.
Ayer, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
MGH West
Waltham, Massachusetts, United States
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States
Oakwood Hospital and Medical Center
Dearborn, Michigan, United States
Henry Ford Hospital
Detroit, Michigan, United States
William Beaumont Hospital
Royal Oak, Michigan, United States
Covenant Center for the Heart
Saginaw, Michigan, United States
United States, Minnesota
Essentia Health East
Duluth, Minnesota, United States
Metropolitan Heart and Vascular Institute
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
United States, Missouri
Missouri Cardiovascular Specialists
Columbia, Missouri, United States
St. Luke's Health System
Kansas City, Missouri, United States
United States, Montana
Glacier View Research Institute
Kalispell, Montana, United States
United States, New Jersey
Advanced Heart Care, LLC
Bridgewater, New Jersey, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Newark Beth Israel Medical Center
Newark, New Jersey, United States
Heart & Vascular Center of NJ/Cardio Metabolic Institute
Somerset, New Jersey, United States
United States, New York
Bronx - Lebanon Hospital Center
Bronx, New York, United States
New York Methodist Hospital
Brooklyn, New York, United States
Columbia University Medical Center
New York, New York, United States
Mount Sinai Medical Center
New York, New York, United States
Cardiology Associates of Schenectady
Schenectady, New York, United States
Stony Brook University Hospital
Stony Brook, New York, United States
SUNY Upstate Medical University
Syracuse, New York, United States
United States, North Carolina
LeBauer Cardiovascular Research Foundation
Greensboro, North Carolina, United States
United States, Ohio
The Lindner Center for Research & Education at The Christ Hospital
Cincinnati, Ohio, United States
Cleveland Clinic
Cleveland, Ohio, United States
Dayton VA Medical Center
Dayton, Ohio, United States
United States, Oklahoma
Oklahoma City VA
Oklahoma City, Oklahoma, United States
Warren Cancer Research Foundation
Tulsa, Oklahoma, United States
United States, Pennsylvania
Lancaster Heart and Stroke Foundation
Lancaster, Pennsylvania, United States
Temple University
Philadelphia, Pennsylvania, United States
Drexel University College of Medicine
Philadelphia, Pennsylvania, United States
Grand View - Lehigh Valley Health Service
Sellersville, Pennsylvania, United States
Lankenau Medical Center
Wynnewood, Pennsylvania, United States
United States, Tennessee
Stern Cardiovascular Foundation, Inc.
Germantown, Tennessee, United States
United States, Texas
CIVA/CArdiovascular Research Institute of Dallas
Dallas, Texas, United States
Michael E. Debakey VA Medical Center
Houston, Texas, United States
United States, Utah
University of Utah
Salt Lake City, Utah, United States
United States, Wisconsin
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, United States
Aspirus Wausau Hospital
Wausau, Wisconsin, United States
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada
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 October 22, 2014