Tadalafil for Pulmonary Hypertension Due to Chronic Lung Disease (TADA-PHILD)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01862536 |
Recruitment Status :
Completed
First Posted : May 24, 2013
Results First Posted : March 9, 2021
Last Update Posted : March 9, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Pulmonary Hypertension Chronic Obstructive Pulmonary Disease (COPD) | Drug: Tadalafil Drug: placebo | Phase 2 |

Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 44 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | Tadalafil for Pulmonary Hypertension Associated With Chronic Lung Disease |
Actual Study Start Date : | October 1, 2013 |
Actual Primary Completion Date : | August 31, 2019 |
Actual Study Completion Date : | August 31, 2019 |

Arm | Intervention/treatment |
---|---|
Placebo Comparator: Placebo
Placebo tablet
|
Drug: placebo
Daily use in double blind study. |
Experimental: Tadalafil
Daily use of tadalafil (study drug) at 40 mg orally.
|
Drug: Tadalafil
Daily use of study drug to treat pulmonary hypertension.
Other Name: Cialis |
- Change in 6 Minute Walk Test [ Time Frame: The change in distance walked when assessed at 3 months following trial initiation as compared to baseline, similarly at 6 months compared to baseline, at 9 months compared to baseline and at 12 months compared to baseline. ]Change from baseline in distance walked in 6 minutes.
- Maximum VO2 [ Time Frame: 12 months ]Measure of aerobic fitness on exercise assessed by cardiopulmonary exercise test.
- Pulmonary Vascular Resistance [ Time Frame: 6 months ]Pulmonary vascular resistance assessed on right heart catheterization is a hemodynamic measurement of pulmonary vascular remodeling.
- Mean Pulmonary Artery Pressure [ Time Frame: 6 months ]Mean pulmonary artery pressure assessed by right heart catheterization is a hemodynamic measurement of pulmonary hypertension severity.
- Tricuspid Annular Plane Excursion (TAPSE) [ Time Frame: 12 months ]The tricuspid annular plane excursion is an echocardiographic measurement of right ventricular systolic dysfunction.
- St. George's Respiratory Questionnaire, Dyspnea and Health Related Quality of Life [ Time Frame: 12 months ]
Disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. There are 50 items, 2 parts, (3 components). Each item is accorded a weight determined by the degree of distress accorded to each symptom or state described.
Scores range from 0-100, with higher scores indicating more limitations
- N-type Brain Natriuretic Peptide (BNP) Concentration [ Time Frame: 12 months ]Plasma BNP concentration is a biochemical marker that correlates positively with pulmonary hypertension severity.
- Resting Hypoxemia [ Time Frame: Early (4 hours and 3 days following treatment) and late (1, 3, 6, 9, 12 months following treatment) ]Changes to resting peripheral oxyhemoglobin saturation levels will be used to assess the safety of the study drug in patients with chronic lung diseases.
- Exercise-induced Hypoxemia [ Time Frame: 12 months ]Changes to peripheral oxyhemoglobin saturation levels on exercise will be used to assess the safety of the study drug in patients with chronic lung diseases.

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, Learn About Clinical Studies.
Ages Eligible for Study: | 40 Years to 85 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male and female U.S. Veteran patients 40-85 years old, with Gold Stage II COPD by pulmonary function testing (FEV1/FVC <0.70; performed within 6 months of recruitment.
-
Eligible subjects must have PH documented on transthoracic echocardiogram within 6 months of baseline visit demonstrating an RV systolic pressure >40mmHg. To confirm the presence of PH, a right-heart catheterization will be performed, with subjects randomized to treatment only if catheterization shows a:
- mPAP >25 mm Hg
- PVR >2.5 Wood units
- pulmonary artery capillary wedge pressure 18 mm Hg or less at rest
-
PH belonging to the following subgroup of the updated Dana Point Clinical Classification:
- Group 3 (PH associated with lung disease and/or hypoxemia) specifically, Group 3.1 (chronic obstructive pulmonary disease [COPD]) as the major criteria. Patients may also have minor clinical features associated with 3.2 (Interstitial disease) (such as mild fibrosis on high resolution chest CT, but total lung capacity>80% predicted) and 3.3 (sleep disordered breathing) (AHI <15 or 20/hour).
- 6-minute walk distance between 50-450 meters at screening visit.
Exclusion Criteria:
- PH belonging to the following subgroups of the updated Dana Point Clinical Classification:
Group 1
- Idiopathic
- heritable
- drug or toxin-induced
-
Associated Pulmonary Arterial Hypertension (APAH) with:
- connective tissue disease
- congenital heart disease
- or HIV
Group 2
- left atrial hypertension
Group 4
- chronic thromboembolic PH
- or other forms of PH not associated with primary lung disease
Also
- Patients with a history of systemic hypotension in the ambulatory setting (reproducible measurements of systolic blood pressure <89 mmHg) on chart review.
- Patients with moderate or severe hepatic impairment (Child-Pugh B and C)
- Patients with severe renal insufficiency (GFR <30 ml/min/1.73 m2)
- Severe aortic stenosis (aortic valve area <1.0 cm2)
-
Patients with any acute or chronic impairment:
- (other than dyspnea), limiting the ability to comply with the study requirements, including the 6-minute walk test and right heart catheterization.
- Patients with a recent stroke
- Patients with untreated hypoxemia (SaO2 <92%) at rest
- Patients with untreated moderate or severe obstructive sleep apnea (AHI>15)
- Patients with any coagulopathy
- Patients requiring nitrate therapy for any clinical indication
- Patients with an active prescription for pulmonary vasodilator medication other than oxygen
- Patients with a history of nonarteritic anterior ischemic optic neuropathy
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Contraindication to tadalafil use including allergy to:
- any PDE-5 inhibitor
- anatomical deformations of the penis
- sickle cell anemia
- multiple myeloma
- leukemia
- bleeding disorders
- active peptic ulcer disease
- retinitis pigmentosa or other retinal disorders.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01862536
United States, California | |
VA Greater Los Angeles Healthcare System, West Los Angeles, CA | |
West Los Angeles, California, United States, 90073 | |
United States, Colorado | |
VA Eastern Colorado Health Care System, Denver, CO | |
Denver, Colorado, United States, 80220 | |
United States, Georgia | |
Atlanta VA Medical and Rehab Center, Decatur, GA | |
Decatur, Georgia, United States, 30033 | |
United States, Massachusetts | |
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA | |
Boston, Massachusetts, United States, 02130 | |
United States, Rhode Island | |
Providence VA Medical Center, Providence, RI | |
Providence, Rhode Island, United States, 02908 |
Principal Investigator: | Ronald H Goldstein, MD | VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA |
Documents provided by VA Office of Research and Development:
Responsible Party: | VA Office of Research and Development |
ClinicalTrials.gov Identifier: | NCT01862536 |
Other Study ID Numbers: |
CLIN-008-12F |
First Posted: | May 24, 2013 Key Record Dates |
Results First Posted: | March 9, 2021 |
Last Update Posted: | March 9, 2021 |
Last Verified: | February 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | The PI will create de-identified, study-specific datasets. The PI will replace social security and medical station numbers with study-specific numbers.
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Time Frame: | - Datasets meeting VA standards for disclosure to the public will be made available within 1 year of publication. |
Access Criteria: | Investigators requesting a copy of a dataset will sign a Letter of Agreement or a Data Use Agreement. The recipient will not attempt to identify any individual whose data are in the dataset. A local privacy officer will certify that a dataset contains no PHI, PII, or VA Sensitive Information prior to release outside VA. |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
Randomized trial COPD tadalafil Phosphodiesterase inhibitor Pulmonary hypertension |
Lung Diseases Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Hypertension, Pulmonary Hypertension Vascular Diseases Cardiovascular Diseases Respiratory Tract Diseases |
Tadalafil Vasodilator Agents Phosphodiesterase 5 Inhibitors Phosphodiesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Urological Agents |