Heart FailurePhase 3PITCH-HFNCT01910389
Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure
A Phase 3 study testing Tadalafil in people with Heart Failure and Pulmonary Hypertension, run by Carelon Research at 63 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Heart Failure, Pulmonary Hypertension
- What is being tested?
- Tadalafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 63 sitesin 2 countries
- Study dates
- Nov 2013to Feb 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
63 sites in 2 countries.
63 sites in 2 countries
United States62 sites
University of Michigan Health System
Ann Arbor, Michigan
Maine Research Associates
Auburn, Maine
University Cardiology Associates LLC
Augusta, Georgia
Primary Care Cardiology Research, Inc.
Ayer, Massachusetts
Johns Hopkins Hospital
Baltimore, Maryland
Brigham and Women's Hospital
Boston, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts
Advanced Heart Care, LLC
Bridgewater, New Jersey
New York Methodist Hospital
Brooklyn, New York
Northwestern University
Chicago, Illinois
University of Illinois Hospital
Chicago, Illinois
The Lindner Center for Research & Education at The Christ Hospital
Cincinnati, Ohio
Cleveland Clinic
Cleveland, Ohio
Missouri Cardiovascular Specialists
Columbia, Missouri
CIVA/CArdiovascular Research Institute of Dallas
Dallas, Texas
Dayton VA Medical Center
Dayton, Ohio
Oakwood Hospital and Medical Center
Dearborn, Michigan
Henry Ford Hospital
Detroit, Michigan
Essentia Health East
Duluth, Minnesota
Eisenhower Army Medical Center
Fort Gordon, Georgia
Broward Health
Fort Lauderdale, Florida
Allianz Medical and Research Center
Fountain Valley, California
Stern Cardiovascular Foundation, Inc.
Germantown, Tennessee
LeBauer Cardiovascular Research Foundation
Greensboro, North Carolina
Hackensack University Medical Center
Hackensack, New Jersey
Michael E. Debakey VA Medical Center
Houston, Texas
Heart Center Inc - Research
Huntsville, Alabama
Glacier View Research Institute
Kalispell, Montana
St. Luke's Health System
Kansas City, Missouri
Lancaster Heart and Stroke Foundation
Lancaster, Pennsylvania
Baptist Health Transplant Institute
Little Rock, Arkansas
Baptist Hospital East
Louisville, Kentucky
Miller School of Medicine University of Miami
Miami, Florida
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin
Metropolitan Heart and Vascular Institute
Minneapolis, Minnesota
LSU Health Sciences Center
New Orleans, Louisiana
Columbia University Medical Center
New York, New York
Mount Sinai Medical Center
New York, New York
Christiana Care Health System
Newark, Delaware
Newark Beth Israel Medical Center
Newark, New Jersey
Oklahoma City VA
Oklahoma City, Oklahoma
Orlando Health
Orlando, Florida
Research Integrity LLC
Owensboro, Kentucky
Methodist Medical Group Cardiology
Peoria, Illinois
Drexel University College of Medicine
Philadelphia, Pennsylvania
Temple University
Philadelphia, Pennsylvania
Charlotte Heart Group Research Center
Port Charlotte, Florida
Mayo Clinic
Rochester, Minnesota
Brevard Cardiovascular Research Associates
Rockledge, Florida
William Beaumont Hospital
Royal Oak, Michigan
Covenant Center for the Heart
Saginaw, Michigan
University of Utah
Salt Lake City, Utah
Cardiology Associates of Schenectady
Schenectady, New York
Grand View - Lehigh Valley Health Service
Sellersville, Pennsylvania
Heart & Vascular Center of NJ/Cardio Metabolic Institute
Somerset, New Jersey
Stony Brook University Hospital
Stony Brook, New York
SUNY Upstate Medical University
Syracuse, New York
Bronx - Lebanon Hospital Center
The Bronx, New York
Warren Cancer Research Foundation
Tulsa, Oklahoma
MGH West
Waltham, Massachusetts
Aspirus Wausau Hospital
Wausau, Wisconsin
Lankenau Medical Center
Wynnewood, Pennsylvania
About this study
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
- Being tested
- Tadalafil, Placebo for tadalafil
- Keywords
- Heart failure, Pulmonary hypertension, tadalafil, Phosphodiesterase Type 5 Inhibition
- Medical subject headings
- Heart Failure, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TadalafilDrug
Also called Adcirca
Placebo for tadalafilDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo for tadalafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Outcome of Cardiovascular (CV) Mortality or Heart Failure (HF) Hospitalization
Measured: Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject
Secondary outcomes (12)
Cardiovascular Mortality
Measured: Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject
Heart Failure Hospitalization
Measured: Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject
All-cause Mortality
Measured: 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)
Measured: Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject
Frequency of CV Hospitalizations
Measured: Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject
Frequency of HF Hospitalizations
Measured: Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject
Change in 6 Minute Walk Distance From Baseline to 3 Months
Measured: Randomization to 3 months
Change in MLHFQ Score From Baseline to 3 Months
Measured: Randomization to 3 months
Change in 6 Minute Walk Distance From Baseline to 18 Months
Measured: Randomization to 18 months
Trend in 6 Minute Walk Distance From Baseline Through 18 Months
Measured: Randomization to 18 months
Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score From Baseline to 18 Months
Measured: Randomization to 18 months
Trend in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score From Baseline Through 18 Months
Measured: Randomization to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2013 (estimated)
- Study startNov 2013
- Primary completionFeb 2014
- Study completionFeb 2014
Why it stopped: terminated by funding agency
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carelon Research
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marc J. Semigran, MD, Principal investigator, Massachusetts General HospitalSusan F Assmann, PhD, Principal investigator, New England Research Institutes, Inc.Flora S Siami, MPH, Principal investigator, New England Research Institutes, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01910389
- Sponsor's protocol ID
- U01HL105463
- Acronym
- PITCH-HF
- Status last verified
- Jan 2014
- First submitted
- 25 Jul 2013
- Last updated
- 4 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure
- ClinicalTrials.gov ID
- NCT01910389
- Acronym / sponsor ID
- PITCH-HF / U01HL105463
- Conditions
- Heart Failure, Pulmonary Hypertension
- Keywords
- Heart failure, Pulmonary hypertension, tadalafil, Phosphodiesterase Type 5 Inhibition
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: terminated by funding agency
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Carelon ResearchUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Massachusetts General Hospital
- Study start
- Nov 2013
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 29 Jul 2013 (estimated)
- Results
- Posted 4 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tadalafil | Active comparator | Drug: TadalafilTadalafil 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. |
| Placebo | Placebo comparator | Drug: Placebo for tadalafilPlacebo 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. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TadalafilAlso: Adcirca | Drug | Tadalafil |
| Placebo for tadalafil | Drug | Placebo |
Primary outcome
Composite Outcome of Cardiovascular (CV) Mortality or Heart Failure (HF) Hospitalization
Time frame: Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject
12 secondary outcomes
Cardiovascular Mortality
Time frame: Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject
Heart Failure Hospitalization
Time frame: Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject
All-cause Mortality
Time frame: 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)
Time frame: Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject
Frequency of CV Hospitalizations
Time frame: Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject
Frequency of HF Hospitalizations
Time frame: Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject
Change in 6 Minute Walk Distance From Baseline to 3 Months
Time frame: Randomization to 3 months
Change in MLHFQ Score From Baseline to 3 Months
Time frame: Randomization to 3 months
Change in 6 Minute Walk Distance From Baseline to 18 Months
Time frame: Randomization to 18 months
Trend in 6 Minute Walk Distance From Baseline Through 18 Months
Time frame: Randomization to 18 months
Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score From Baseline to 18 Months
Time frame: Randomization to 18 months
Trend in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score From Baseline Through 18 Months
Time frame: Randomization to 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc J. Semigran, MD principal investigator
Massachusetts General Hospital
Susan F Assmann, PhD principal investigator
New England Research Institutes, Inc.
Flora S Siami, MPH principal investigator
New England Research Institutes, Inc.
63 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tadalafil in people with Heart Failure and Pulmonary Hypertension, run by Carelon Research at 63 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 63 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite Outcome of Cardiovascular (CV) Mortality or Heart Failure (HF) Hospitalization (time frame: Randomization through each subject's last semi-annual visit, up to a maximum of 3 years per subject). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2015.