Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure

Heart Failure Clinical Trial

— PITCH-HF  

Official title:

Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01910389
• Other study ID #: U01HL105463
• Status: Terminated
• Phase: Phase 3
• First received: July 25, 2013
• Last updated: April 16, 2015
• Start date: November 2013
• Est. completion date: February 2014

Study information

• Verified date: January 2014
• Source: New England Research Institutes
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Data and Safety Monitoring Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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 ß-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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Drug:
• Tadalafil

• Placebo for tadalafil

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
New England Research Institutes	Massachusetts General Hospital, National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite Outcome of Cardiovascular (CV) Mortality or Heart Failure (HF) Hospitalization		Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject	No
Secondary	Cardiovascular Mortality		Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject	No
Secondary	Heart Failure Hospitalization		Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject	No
Secondary	All-cause Mortality		Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject	No
Secondary	Composite Outcome of All-cause Mortality or CV Hospitalization (Myocardial Infarction, Acute Coronary Syndrome, Stroke, Arrhythmia, or Heart Failure)		Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject	No
Secondary	Frequency of CV Hospitalizations		Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject	No
Secondary	Frequency of HF Hospitalizations		Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject	No
Secondary	Change in 6 Minute Walk Distance From Baseline to 3 Months		Randomization to 3 months	No
Secondary	Change in MLHFQ Score From Baseline to 3 Months		Randomization to 3 months	No
Secondary	Change in 6 Minute Walk Distance From Baseline to 18 Months		Randomization to 18 months	No
Secondary	Trend in 6 Minute Walk Distance From Baseline Through 18 Months		Randomization to 18 months	No
Secondary	Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score From Baseline to 18 Months		Randomization to 18 months	No
Secondary	Trend in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score From Baseline Through 18 Months		Randomization to 18 months	No