Effect of PDE5 Inhibitor on Respiratory Symptoms in COPD Complicated by Pulmonary Hypertension
The investigators will study whether the drug tadalafil improves shortness of breath in 126 Veterans with Chronic Obstructive Pulmonary Disease (COPD) and high blood pressure in the lungs. The investigators will also assess whether tadalafil improves quality of life, home daily physical activity, exercise endurance, the frequency of acute flares of COPD, blood pressure in the lungs, and lung function. Veterans who enroll in the trial will be allocated by chance to either active tadalafil or an inactive identical capsule (placebo). Neither the Veteran nor the investigator will know whether the Veteran is taking tadalafil or placebo. Veterans will be followed closely in clinic or by telephone at 1, 2, 3, 4, 5, and 6 months, with attention to side effects and safety. At 1,3, and 6 months the investigators will repeat the questionnaires and testing of blood pressures in the lung and lung function. The investigators anticipate that the results of this study will determine whether tadalafil improves shortness of breath when added to usual medications for COPD.
• Outpatients with COPD, defined as airflow limitation with post-bronchodilator obstruction on baseline visit spirometry, identified by FEV1/FVC \< 70% or \< the lower limit of normal (5th percentile of a normal population based on Global Lung Function Initiative reference equations), OR any emphysema on chest CT noted in a clinical radiology report confirmed by study investigator review.
• Eligible subjects must have PH documented as follows:
‣ Main Pulmonary Artery/Ascending Aorta (PA/A) diameter \> 1.0 on clinically available CT scans within 12 months OR
⁃ outpatient echocardiography done within 6 months of enrollment demonstrating PA sys \> 34 mmHg OR
⁃ Mean Pulmonary Artery Pressure \> 20 on Right Heart Catheterization done within 6 months of enrollment and when Veteran is clinically stable.
• Eligible subjects must be dyspneic, as quantitated by a score of at least 20 on the baseline UCSD Shortness of Breath Questionnaire, assessed at the time of the baseline visit.
• Treatment with at least one long-acting bronchodilator for at least 4 weeks, assessed at the time of the baseline visit by chart review and patient interview.
• Age 35-89 Years
• Women of childbearing potential must meet one of the following criteria for the previous three months AND must have a negative pregnancy test on the day of testing. If more than 36 hours since the participant's last pregnancy test, they will be tested again at the study visit.
‣ have been using a contraceptive measure (an intrauterine device (IUD), a contraceptive implant, oral contraceptives, barrier methods, or abstinence)
⁃ have a male partner with a vasectomy
⁃ have a tubal ligation procedure or a medical diagnosis (such as infertility) or therapies/procedures that precludes pregnancy (such as cancer treatments or endometrial ablation)
⁃ are in a same-sex relationship
⁃ have a male partner not capable of fathering children because of congenital anomalies, other surgery, or medical treatment
• Women who are not considered to be of childbearing potential who have been surgically sterilized (for example: removal of ovaries or fallopian tubes, or hysterectomy) or are post-menopausal (no menstrual period for more than 6 months).