Phosphodiesterase Type 5 Inhibition With Tadalafil Change... | NCT01910389

NCT01910389

Status Module

Sponsor/Collaborators Module

Name	Class
National Heart, Lung, and Blood Institute (NHLBI)	NIH
Massachusetts General Hospital	OTHER

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Tadalafil	Drug		Tadalafil	Adcirca
Placebo for tadalafil

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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

Eligibility Module

Eligibility 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/Locations Module

Overall Officials

Name	Affiliation	Role
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

Facility	Status	City	State	ZIP	Country	Contacts
Heart Center Inc - Research		Huntsville	Alabama		United States
Baptist Health Transplant Institute

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Median

Inter-Quartile Range

years

Title

Denominators

Categories

Title	Measurements
	BG00062.6(42.3 to 72.5) BG00163.3(51.7 to 76.8) BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0002 BG0011 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0001 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Composite Outcome of Cardiovascular (CV) Mortality or Heart Failure (HF) Hospitalization

Trial was terminated early. Data for outcome not obtained.

Posted

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG0000 OG0010

Secondary

Cardiovascular Mortality

Trial was terminated early. Data for outcome not obtained.

Posted

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Heart Failure Hospitalization

Trial was terminated early. Data for outcome not obtained.

Posted

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

All-cause Mortality

Trial was terminated early. Data for outcome not obtained.

Posted

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Composite Outcome of All-cause Mortality or CV Hospitalization (Myocardial Infarction, Acute Coronary Syndrome, Stroke, Arrhythmia, or Heart Failure)

Trial was terminated early. Data for outcome not obtained.

Posted

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Frequency of CV Hospitalizations

Trial was terminated early. Data for outcome not obtained.

Posted

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Frequency of HF Hospitalizations

Trial was terminated early. Data for outcome not obtained.

Posted

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Change in 6 Minute Walk Distance From Baseline to 3 Months

Trial was terminated early. Data for outcome not obtained.

Posted

Randomization to 3 months

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Change in MLHFQ Score From Baseline to 3 Months

Trial was terminated early. Data for outcome not obtained.

Posted

Randomization to 3 months

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Change in 6 Minute Walk Distance From Baseline to 18 Months

Trial was terminated early. Data for outcome not obtained.

Posted

Randomization to 18 months

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Trend in 6 Minute Walk Distance From Baseline Through 18 Months

Trial was terminated early. Data for outcome not obtained.

Posted

Randomization to 18 months

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score From Baseline to 18 Months

Trial was terminated early. Data for outcome not obtained.

Posted

Randomization to 18 months

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Trend in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score From Baseline Through 18 Months

Trial was terminated early. Data for outcome not obtained.

Posted

Randomization to 18 months

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.			4	15	3	15
EG001	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.			2	8	0	8

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
CHF EXACERBATION	Cardiac disorders	Systematic Assessment	EG0000 events0 affected15 at risk EG0012 events1 affected8 at risk
CHF EXACERBATION, DYSPNEA	Cardiac disorders	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected8 at risk
CONGESTIVE HEART FAILURE	Cardiac disorders	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected8 at risk
HOSPITALIZATION FOR DECOMPENSATED HEART FAILURE	Cardiac disorders	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected8 at risk
ER ADMISSION; NOSEBLEED	General disorders	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected8 at risk
SEPSIS	Infections and infestations	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected8 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
DIARRHEA	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected8 at risk
FLUSHING	Vascular disorders	Systematic Assessment	EG0003 events1 affected15 at risk EG0010 events0 affected8 at risk
HEADACHE	Nervous system disorders	Systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected8 at risk
HYPOGLYCEMIA	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected8 at risk
INSOMNIA	Psychiatric disorders	Systematic Assessment	EG0002 events1 affected15 at risk EG0010 events0 affected8 at risk
METALLIC TASTE TO FOOD	General disorders	Systematic Assessment	EG0002 events1 affected15 at risk EG0010 events0 affected8 at risk
PALPITATIONS	Cardiac disorders	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected8 at risk
STOMACH UPSET	Gastrointestinal disorders	Systematic Assessment	EG0002 events1 affected15 at risk EG0010 events0 affected8 at risk

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

Certain Agreements

ID	Term
D006333	Heart Failure
D006976	Hypertension, Pulmonary

ID	Term
D000068581	Tadalafil

Ancestor Terms

ID	Term
D002243	Carbolines
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D026121	Indole Alkaloids
D007211	Indoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006575	Heterocyclic Compounds, 3-Ring

ID	Term
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D006973	Hypertension
D014652	Vascular Diseases