Breathe Easier With Tadalafil Therapy for Dyspnea in COPD-PH

NCT05937854 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: PULM-002-22FI01CX002543
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Chronic Obstructive Pulmonary Disease; Pulmonary Hypertension; Dyspnea

Keywords

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

Outcome Measures

Primary Outcomes (1)

• severity of patient-reported dyspnea

  Assessed by the University of California-San Diego Shortness of Breath Questionnaire (UCSD-SOBQ). Score range = 0-120 with higher scores indicating worse outcomes. Minimum score for inclusion in the study is 10.

  6 months

Secondary Outcomes (3)

• physical activity

  6 months

• clinically important deterioration

  6 months

• functional exercise capacity

  6 months

Other Outcomes (2)

• Pulmonary artery to aorta diameter ratio

  6 months

• Estimated PA systolic pressure in mm Hg

  6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Encapsulated placebo one or 2 encapsulated tablets po QD

Drug: Placebo

tadalafil

ACTIVE COMPARATOR

one or 2 encapsulated tablets of encapsulated tadalafil (20MG) po QD

Drug: Tadalafil

Interventions

Tadalafil DRUG

one or 2 encapsulated tablets of encapsulated tadalafil (20MG) po QD

Also known as: Adcirca, Cialis

tadalafil

Placebo DRUG

one or two encapsulated tablets of placebo po QD

Placebo

Eligibility Criteria

• Age: 35 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \> 0.90 on clinically available CT scans within 12 months OR
• Main Pulmonary Artery diameter \> 30.8mm 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

You may not qualify if:

• Diagnosis of PH in the following subgroups of the updated WHO Clinical Classification:
• Group 1 (Idiopathic, heritable, drug- or toxin-induced, Pulmonary Arterial Hypertension associated with connective tissue disease, congenital heart disease)
• Group 2 (left atrial hypertension)
• Group 3 PH not attributable to COPD
• Group 4 (chronic thromboembolic PH) or other forms of PH not associated with primary lung disease.
• Systemic hypotension in the ambulatory setting (at least 3 reproducible measurements of systolic BP \<89 mmHg, recorded by a health care provider over 1 week).
• Moderate or severe hepatic impairment (Child-Pugh B and C).
• Severe renal insufficiency (GFR \<30 ml/min/1.73 m2)
• Echocardiography within 3 months 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%. Any aortic or mitral valve replacement.
• Any acute or chronic impairment (other than dyspnea) that limits ability to comply with the study requirements.
• Current unstable angina, myocardial infarction or stroke within 6 months.
• Requirement for nitrate therapy for any clinical indication.
• Active prescription for a PDE-5 inhibitor or other pulmonary vasodilator other than oxygen as a PH treatment.
• History of the following retinal disorders: retinitis pigmentosa, non-arteritic anterior ischemic optic neuropathy, or crowded optic disc noted on ophthalmology examinations recorded in CPRS.
• 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 listed above. 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead
• VA Boston Healthcare System: collaborator
• Atlanta VA Medical Center: collaborator
• VA Eastern Colorado Health Care System: collaborator
• VA Nebraska Western Iowa Health Care System: collaborator

Study Sites (5)

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, 80045, United States

RECRUITING

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033-4004, United States

RECRUITING

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

Boston, Massachusetts, 02130-4817, United States

RECRUITING

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

Omaha, Nebraska, 68105-1850, United States

RECRUITING

Providence VA Medical Center, Providence, RI

Providence, Rhode Island, 02908-4734, United States

RECRUITING

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Hypertension, Pulmonary; Dyspnea; Cigarette Smoking; Motor Activity

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hypertension; Vascular Diseases; Cardiovascular Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Tobacco Smoking; Smoking; Behavior; Tobacco Use

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Sharon I Rounds, MD

  Providence VA Medical Center, Providence, RI

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sharon I Rounds, MD

CONTACT

(401) 273-7100; sharon.rounds@va.gov

Ronald H Goldstein, MD

CONTACT

(857) 203-6578; Ronald.Goldstein@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be assigned a study code
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: double blind placebo-controlled

Study Record Dates

• First Submitted: June 27, 2023
• First Posted: July 10, 2023
• Study Start: April 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Above will be shared upon approval of the study.
• Access Criteria: Individual participant data will be shared within one year of publication of results.

Locations

US (5)