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Tadalafil for Pulmonary Hypertension Due to Chronic Lung Disease (TADA-PHILD)

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. Identifier: NCT01862536
Recruitment Status : Completed
First Posted : May 24, 2013
Results First Posted : March 9, 2021
Last Update Posted : March 9, 2021
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:
The functional, social, and economic burden of chronic obstructive lung disease (COPD) on the healthcare system is extraordinary. COPD is the fourth leading cause of death in the United States, and some estimates attribute up to $33.2 billion in health care costs to COPD-associated morbidity and mortality annually. The burden of COPD to the VA Healthcare system parallels these findings. According to the VA HSR&D Health Economics Resource Center, COPD ranks 5th among the 40 most common chronic clinical conditions in the U.S. Veteran patient population, is responsible for >14,000 VA hospital admission annually, and increases by $1,051/patient the total annual health care cost burden on the VA Healthcare system. Importantly, COPD is associated with frequent emergency room visitation and/or hospitalization patients. Pulmonary hypertension is a common co-morbid condition that worsen morbidity and mortality in patients with COPD. This study will examine the potential for tadalafil, a phosphodiesterase type-5 (PDE-5) inhibitor to improve functional status by decreasing pulmonary hypertension. Results from this study are expected to define the potential use of PDE-5 inhibitors in COPD-induced pulmonary hypertension. If successful, this treatment option may improve quality of life and outcomes for the large number of Veterans afflicted with PH due to COPD.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Chronic Obstructive Pulmonary Disease (COPD) Drug: Tadalafil Drug: placebo Phase 2

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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

Resource links provided by the National Library of Medicine

Drug Information available for: Tadalafil

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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Maximum VO2 [ Time Frame: 12 months ]
    Measure of aerobic fitness on exercise assessed by cardiopulmonary exercise test.

  2. Pulmonary Vascular Resistance [ Time Frame: 6 months ]
    Pulmonary vascular resistance assessed on right heart catheterization is a hemodynamic measurement of pulmonary vascular remodeling.

  3. 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.

  4. Tricuspid Annular Plane Excursion (TAPSE) [ Time Frame: 12 months ]
    The tricuspid annular plane excursion is an echocardiographic measurement of right ventricular systolic dysfunction.

  5. 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

  6. 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.

  7. 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.

  8. 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.

Information from the National Library of Medicine

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.

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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


  • 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
  • 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.

Information from the National Library of Medicine

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 identifier (NCT number): NCT01862536

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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
Sponsors and Collaborators
VA Office of Research and Development
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Principal Investigator: Ronald H Goldstein, MD VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
  Study Documents (Full-Text)

Documents provided by VA Office of Research and Development:
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Responsible Party: VA Office of Research and Development 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.

  • A local privacy officer will certify that a dataset contains no PHI, PII, or VA Sensitive Information prior to release outside VA.
  • Final data sets will be maintained locally on a secure server or comparable data storage appliance inside the VA network until enterprise-level resources become available for long-term storage and access.
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.

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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
Keywords provided by VA Office of Research and Development:
Randomized trial
Phosphodiesterase inhibitor
Pulmonary hypertension
Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Respiratory Tract Diseases
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents