What is the mechanism of action of this treatment?

Tadalafil, a Phosphodiesterase-5 (PDE-5) inhibitor, alleviates shortness of breath by relaxing blood vessels and improving blood flow, which is particularly beneficial for patients with COPD and pulmonary hypertension. This reduces the workload on the heart and lungs, easing breathing. Other common treatments include beta-2 agonists and muscarinic antagonists, which relax airway muscles, and inhaled glucocorticoids, which reduce airway inflammation. These mechanisms are essential for managing symptoms and enhancing the quality of life in patients with chronic respiratory conditions.

What side effects are associated with this type of intervention?

Phosphodiesterase-5 Inhibitors (PDE5Is) like tadalafil, used for treating conditions such as pulmonary hypertension that cause shortness of breath, commonly have side effects including headache, flushing, dyspepsia, nasal congestion, and visual disturbances. There is also a risk of hypotension, particularly when combined with other medications such as guanylate cyclase stimulants.

What prior FDA approvals exist?

Phosphodiesterase-5 Inhibitors, such as sildenafil, have been studied and used for the treatment of pulmonary arterial hypertension (PAH), which can cause shortness of breath. The STARTS-1 and STARTS-2 trials demonstrated that sildenafil improved exercise capacity and pulmonary hemodynamics in pediatric patients with PAH. Although there were initial concerns about increased mortality with higher doses, further analysis suggested potential benefits with careful monitoring. This background supports the investigation of tadalafil, another Phosphodiesterase-5 Inhibitor, for similar pulmonary conditions.

What other types of research exist?

Promising alternatives to Tadalafil for treating shortness of breath in patients with COPD and pulmonary hypertension include: <ol> <li>Roflumilast: A phosphodiesterase-4 inhibitor with anti-inflammatory effects, shown to reduce COPD exacerbations.</li> <li></li> </ol> Inhaled Treprostinil: A prostacyclin analog that has demonstrated improvements in exercise capacity and reduction in NT-proBNP levels in patients with pulmonary hypertension. 3. Riociguat: A soluble guanylate cyclase stimulator that improves exercise tolerance and pulmonary vascular resistance in patients with pulmonary hypertension. 4. Selexipag: An oral prostacyclin receptor agonist that reduces hospitalizations and slows disease progression in pulmonary arterial hypertension.

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Tadalafil for COPD with Pulmonary Hypertension (BETTER COPD-PH Trial)

Phase 2

Recruiting

Led By Sharon I Rounds, MD

Research Sponsored by VA Office of Research and Development

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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.

Be older than 18 years old

Must not have

Echocardiography showing moderate or greater aortic stenosis (aortic valve area <1.0 cm2), moderate-severe 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%.

Hypoxia (reproducible ambulatory SaO2 < 90% on supplemental oxygen at rest recorded by a health care provider over 1 week).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 months

Summary

This trial is testing whether tadalafil can help Veterans with COPD and high blood pressure in the lungs by reducing shortness of breath and improving overall health. The drug works by relaxing blood vessels to improve blood flow. The study will compare tadalafil to another group over several months to see if it makes a significant difference in symptoms and quality of life. Tadalafil received FDA approval in 2009 for the treatment of pulmonary arterial hypertension (PAH) and has shown to improve exercise capacity and quality of life in patients.

Who is the study for?

Veterans aged 35-89 with COPD and pulmonary hypertension (PH), experiencing shortness of breath, who are already on long-term bronchodilator therapy. They must have specific heart function and lung capacity as shown by recent tests. Excluded are those with certain heart conditions, recent major cardiovascular events, severe liver or kidney disease, other impairments affecting study compliance, pregnant or breastfeeding women, and those on conflicting medications.

What is being tested?

The trial is testing if tadalafil can help ease shortness of breath in veterans with COPD-PH compared to a placebo. It also looks at quality of life improvements and physical activity levels. Participants will be randomly assigned to either the drug or placebo group without knowing which one they're receiving and monitored for six months through clinic visits and calls.

What are the potential side effects?

Tadalafil may cause headaches, indigestion, back pain, muscle aches, flushing, stuffy or runny nose. These side effects usually go away after a few hours but back pain and muscle aches can last up to two days.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have COPD confirmed by a lung function test or chest CT.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My heart's valves are not working properly, or my heart is not pumping well.

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My oxygen levels fall below 90% even with extra oxygen.

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I am currently taking a protease inhibitor, anti-fungal agent, or rifampin.

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My liver is not working well (moderate to severe issues).

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I have a history of specific eye nerve damage or a crowded optic disc.

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I have been diagnosed with a specific type of pulmonary hypertension.

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I need nitrate therapy for my condition.

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I have been diagnosed with Obstructive Sleep Apnea but haven't been prescribed any treatment.

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I have had a worsening of my COPD or heart failure in the last 4 weeks.

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I am currently taking doxazosin.

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My kidney function is severely reduced.

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I am currently prescribed medication for pulmonary hypertension other than oxygen.

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I have been diagnosed with a rare lung blood vessel disorder.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

severity of patient-reported dyspnea

Secondary study objectives

clinically important deterioration

functional exercise capacity

physical activity

Other study objectives

Estimated PA systolic pressure in mm Hg

Pulmonary artery to aorta diameter ratio

Trial Design

2Treatment groups

Active Control

Placebo Group

Group I: tadalafilActive Control1 Intervention

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

Group II: PlaceboPlacebo Group1 Intervention

Encapsulated placebo one or 2 encapsulated tablets po QD

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Tadalafil, a Phosphodiesterase-5 (PDE-5) inhibitor, alleviates shortness of breath by relaxing blood vessels and improving blood flow, which is particularly beneficial for patients with COPD and pulmonary hypertension. This reduces the workload on the heart and lungs, easing breathing. Other common treatments include beta-2 agonists and muscarinic antagonists, which relax airway muscles, and inhaled glucocorticoids, which reduce airway inflammation. These mechanisms are essential for managing symptoms and enhancing the quality of life in patients with chronic respiratory conditions.

Measuring functional status in chronic lung disease: conclusions from a randomized control trial.[Peroral terbutaline in the treatment of patients with severe irreversible obstructive pulmonary disease].A comparison of the effects of different methods of administration of beta-2-sympathomimetics in patients with asthma.