RECRUITING

Breathe Easier With Tadalafil Therapy for Dyspnea in COPD-PH

Conditions

Chronic Obstructive Pulmonary Disease Pulmonary Hypertension Dyspnea COPD cigarette smoke lung echocardiography chest CT physical activity spirometry clinically important deterioration

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Effect of PDE5 Inhibitor on Respiratory Symptoms in COPD Complicated by Pulmonary Hypertension

Quick Facts

Study Start:2024-04-01

Study Completion:2027-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05937854

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:35 Years to 89 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. 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. 2. Eligible subjects must have PH documented as follows: * Main Pulmonary Artery/Ascending Aorta (PA/A) diameter \> 1.0 on clinically available CT scans AND transthoracic outpatient echocardiography showing normal LVEF with no evidence of greater than moderate aortic stenosis or mitral regurgitation or diastolic dysfunction. Previous CT scan within 12 months of enrollment and echocardiogram done within 3 months of enrollment. * outpatient echocardiography done within 3 months of enrollment demonstrating PA sys \> 40 mmHg AND normal LVEF with no evidence of greater than moderate aortic stenosis or mitral regurgitation or diastolic dysfunction 1. have been using a contraceptive measure (an intrauterine device (IUD), a contraceptive implant, oral contraceptives, barrier methods, or abstinence) 2. have a male partner with a vasectomy 3. 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) 4. are in a same-sex relationship 5. have a male partner not capable of fathering children because of congenital anomalies, other surgery, or medical treatment	3. Moderate or severe hepatic impairment (Child-Pugh B and C). 4. Severe renal insufficiency (GFR \<30 ml/min/1.73 m2) 5. Echocardiography showing greater than moderate aortic stenosis (aortic valve area \<1.0 cm2), greater than moderate mitral regurgitation, or diastolic dysfunction (Any two of the following: Average E/e' \>14, Septal e' velocity \< 7 or lateral e' velocity \<10, LA volume index \> 34 ml/m2). LVEF \< 50%. 6. Any acute or chronic impairment (other than dyspnea) that limits ability to comply with the study requirements. 7. Current unstable angina, myocardial infarction or stroke within 6 months. 8. Requirement for nitrate therapy for any clinical indication. 9. Active prescription for a PDE-5 inhibitor or other pulmonary vasodilator other than oxygen as a PH treatment. 10. History of retinal disorders including retinitis pigmentosa, non-arteritic anterior ischemic optic neuropathy or crowded optic disc noted on ophthalmology examinations recorded in CPRS. 11. Contraindications: PDE-5i allergy, penile anatomical deformations, sickle cell anemia, multiple myeloma, leukemia, bleeding disorders, active peptic ulcer disease, retinitis pigmentosa or other retinal disorders. In accordance with 38 USC 7332, this information will be kept confidential and will not be disclosed in presentations, publications, or any other dissemination of the study results, or to anyone outside of the IRB-approved study team. 12. Use of any of the following: rifampin, systemic anti-fungal azole agents, protease inhibitors, phenobarbitol, dilantin. 13. Pregnant, possibly pregnant by report, or breastfeeding women. 14. Pulmonary veno-occlusive disease 16. Hypoxia (reproducible ambulatory SaO2 \< 90% on supplemental oxygen at rest recorded by a health care provider over 1 week). 17. Diagnosis of Obstructive Sleep Apnea without a prescription for treatment. 18. Newly prescribed (less than 4 weeks duration) bronchodilator or diuretic therapy or new enrollment in pulmonary rehabilitation at the time of Screening. 19. Students, VA employees, persons with impaired decision making, illiterate and non-English speakers, and terminally ill patients. 20. Nonadherence to accepted GOLD guidelines for treatment of COPD. 21. COPD or CHF exacerbation within the past 4 weeks. 22. On-going therapy with doxazosin.

Inclusion Criteria

Exclusion Criteria

1. 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.
2. Eligible subjects must have PH documented as follows:
* Main Pulmonary Artery/Ascending Aorta (PA/A) diameter \> 1.0 on clinically available CT scans AND transthoracic outpatient echocardiography showing normal LVEF with no evidence of greater than moderate aortic stenosis or mitral regurgitation or diastolic dysfunction. Previous CT scan within 12 months of enrollment and echocardiogram done within 3 months of enrollment.
* outpatient echocardiography done within 3 months of enrollment demonstrating PA sys \> 40 mmHg AND normal LVEF with no evidence of greater than moderate aortic stenosis or mitral regurgitation or diastolic dysfunction
1. have been using a contraceptive measure (an intrauterine device (IUD), a contraceptive implant, oral contraceptives, barrier methods, or abstinence)
2. have a male partner with a vasectomy
3. 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)
4. are in a same-sex relationship
5. have a male partner not capable of fathering children because of congenital anomalies, other surgery, or medical treatment

3. Moderate or severe hepatic impairment (Child-Pugh B and C). 4. Severe renal insufficiency (GFR \<30 ml/min/1.73 m2) 5. Echocardiography showing greater than moderate aortic stenosis (aortic valve area \<1.0 cm2), greater than moderate mitral regurgitation, or diastolic dysfunction (Any two of the following: Average E/e' \>14, Septal e' velocity \< 7 or lateral e' velocity \<10, LA volume index \> 34 ml/m2). LVEF \< 50%.
6. Any acute or chronic impairment (other than dyspnea) that limits ability to comply with the study requirements.
7. Current unstable angina, myocardial infarction or stroke within 6 months. 8. Requirement for nitrate therapy for any clinical indication. 9. Active prescription for a PDE-5 inhibitor or other pulmonary vasodilator other than oxygen as a PH treatment.
10. History of retinal disorders including retinitis pigmentosa, non-arteritic anterior ischemic optic neuropathy or crowded optic disc noted on ophthalmology examinations recorded in CPRS.
11. Contraindications: PDE-5i allergy, penile anatomical deformations, sickle cell anemia, multiple myeloma, leukemia, bleeding disorders, active peptic ulcer disease, retinitis pigmentosa or other retinal disorders. In accordance with 38 USC 7332, this information will be kept confidential and will not be disclosed in presentations, publications, or any other dissemination of the study results, or to anyone outside of the IRB-approved study team.
12. Use of any of the following: rifampin, systemic anti-fungal azole agents, protease inhibitors, phenobarbitol, dilantin.
13. Pregnant, possibly pregnant by report, or breastfeeding women. 14. Pulmonary veno-occlusive disease 16. Hypoxia (reproducible ambulatory SaO2 \< 90% on supplemental oxygen at rest recorded by a health care provider over 1 week).
17. Diagnosis of Obstructive Sleep Apnea without a prescription for treatment. 18. Newly prescribed (less than 4 weeks duration) bronchodilator or diuretic therapy or new enrollment in pulmonary rehabilitation at the time of Screening.
19. Students, VA employees, persons with impaired decision making, illiterate and non-English speakers, and terminally ill patients.
20. Nonadherence to accepted GOLD guidelines for treatment of COPD. 21. COPD or CHF exacerbation within the past 4 weeks. 22. On-going therapy with doxazosin.

Contacts and Locations

Study Contact

Sharon I Rounds, MD

CONTACT

(401) 273-7100

sharon.rounds@va.gov

Ronald H Goldstein, MD

CONTACT

(857) 203-6578

Ronald.Goldstein@va.gov

Principal Investigator

Sharon I Rounds, MD

PRINCIPAL_INVESTIGATOR

Providence VA Medical Center, Providence, RI

Study Locations (Sites)

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, 80045

United States

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033-4004

United States

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, 02130-4817

United States

Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE

Omaha, Nebraska, 68105-1850

United States

Providence VA Medical Center, Providence, RI

Providence, Rhode Island, 02908-4734

United States

Collaborators and Investigators

Sponsor: VA Office of Research and Development

Sharon I Rounds, MD, PRINCIPAL_INVESTIGATOR, Providence VA Medical Center, Providence, RI

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-04-01

Study Completion Date2027-12-01

Study Record Updates

Study Start Date2024-04-01

Study Completion Date2027-12-01

Terms related to this study

Keywords Provided by Researchers

COPD
cigarette smoke
lung
echocardiography
chest CT
physical activity
spirometry
dyspnea
clinically important deterioration

Additional Relevant MeSH Terms

Chronic Obstructive Pulmonary Disease
Pulmonary Hypertension
Dyspnea