Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure

NCT01910389 | Terminated Phase 3 Results DMC

• 1 other identifier: U01HL105463
• Study Type: interventional
• Target: 23
• Locations: 2 countries
• Sites: 63

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.

Conditions

Heart Failure; Pulmonary Hypertension

Keywords

Heart failure; Pulmonary hypertension; tadalafil; Phosphodiesterase Type 5 Inhibition

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (12)

• Cardiovascular Mortality

  Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject

• Heart Failure Hospitalization

  Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject

• All-cause Mortality

  Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject

• 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

• Frequency of CV Hospitalizations

  Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject

Study Arms (2)

Tadalafil

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Tadalafil DRUG

Also known as: Adcirca

Tadalafil

Placebo for tadalafil DRUG

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Carelon Research: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Massachusetts General Hospital: collaborator

Study Sites (63)

Heart Center Inc - Research

Huntsville, Alabama, United States

Location

Baptist Health Transplant Institute

Little Rock, Arkansas, United States

Location

Allianz Medical and Research Center

Fountain Valley, California, United States

Location

Christiana Care Health System

Newark, Delaware, United States

Location

Broward Health

Fort Lauderdale, Florida, United States

Location

Miller School of Medicine University of Miami

Miami, Florida, United States

Location

Orlando Health

Orlando, Florida, United States

Location

Charlotte Heart Group Research Center

Port Charlotte, Florida, United States

Location

Brevard Cardiovascular Research Associates

Rockledge, Florida, United States

Location

University Cardiology Associates LLC

Augusta, Georgia, United States

Location

Eisenhower Army Medical Center

Fort Gordon, Georgia, United States

Location

Northwestern University

Chicago, Illinois, United States

Location

University of Illinois Hospital

Chicago, Illinois, United States

Location

Methodist Medical Group Cardiology

Peoria, Illinois, United States

Location

Baptist Hospital East

Louisville, Kentucky, United States

Location

Research Integrity LLC

Owensboro, Kentucky, United States

Location

LSU Health Sciences Center

New Orleans, Louisiana, United States

Location

Maine Research Associates

Auburn, Maine, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, United States

Location

Primary Care Cardiology Research, Inc.

Ayer, Massachusetts, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, United States

Location

MGH West

Waltham, Massachusetts, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, United States

Location

Oakwood Hospital and Medical Center

Dearborn, Michigan, United States

Location

Henry Ford Hospital

Detroit, Michigan, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, United States

Location

Covenant Center for the Heart

Saginaw, Michigan, United States

Location

Essentia Health East

Duluth, Minnesota, United States

Location

Metropolitan Heart and Vascular Institute

Minneapolis, Minnesota, United States

Location

Mayo Clinic

Rochester, Minnesota, United States

Location

Missouri Cardiovascular Specialists

Columbia, Missouri, United States

Location

St. Luke's Health System

Kansas City, Missouri, United States

Location

Glacier View Research Institute

Kalispell, Montana, United States

Location

Advanced Heart Care, LLC

Bridgewater, New Jersey, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Location

Heart & Vascular Center of NJ/Cardio Metabolic Institute

Somerset, New Jersey, United States

Location

New York Methodist Hospital

Brooklyn, New York, United States

Location

Columbia University Medical Center

New York, New York, United States

Location

Mount Sinai Medical Center

New York, New York, United States

Location

Cardiology Associates of Schenectady

Schenectady, New York, United States

Location

Stony Brook University Hospital

Stony Brook, New York, United States

Location

SUNY Upstate Medical University

Syracuse, New York, United States

Location

Bronx - Lebanon Hospital Center

The Bronx, New York, United States

Location

LeBauer Cardiovascular Research Foundation

Greensboro, North Carolina, United States

Location

The Lindner Center for Research & Education at The Christ Hospital

Cincinnati, Ohio, United States

Location

Cleveland Clinic

Cleveland, Ohio, United States

Location

Dayton VA Medical Center

Dayton, Ohio, United States

Location

Oklahoma City VA

Oklahoma City, Oklahoma, United States

Location

Warren Cancer Research Foundation

Tulsa, Oklahoma, United States

Location

Lancaster Heart and Stroke Foundation

Lancaster, Pennsylvania, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, United States

Location

Temple University

Philadelphia, Pennsylvania, United States

Location

Grand View - Lehigh Valley Health Service

Sellersville, Pennsylvania, United States

Location

Lankenau Medical Center

Wynnewood, Pennsylvania, United States

Location

Stern Cardiovascular Foundation, Inc.

Germantown, Tennessee, United States

Location

CIVA/CArdiovascular Research Institute of Dallas

Dallas, Texas, United States

Location

Michael E. Debakey VA Medical Center

Houston, Texas, United States

Location

University of Utah

Salt Lake City, Utah, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Location

Aspirus Wausau Hospital

Wausau, Wisconsin, United States

Location

Jewish General Hospital

Montreal, Quebec, Canada

Location

MeSH Terms

Conditions

Heart Failure; Hypertension, Pulmonary

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Limitations and Caveats

Early termination leading to small numbers of subjects. Outcome measure data not obtained.

Results Point of Contact

• Title: Brian Harty
• Organization: New England Research Institutes

bhartY@neriscience.com

617-972-3224

Study Officials

• 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.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2013
• First Posted: July 29, 2013
• Study Start: November 1, 2013
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: May 4, 2015
• Results First Posted: May 4, 2015

Record last verified: 2014-01

Locations

US (62); CA (1)