Tadalafil for COPD with Pulmonary Hypertension

(BETTER COPD-PH Trial)

Recruiting at4 trial locations

Overseen by Sharon I Rounds, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: VA Office of Research and Development

Must be taking: Long-acting bronchodilators

Must not be taking: Nitrates, PDE-5 inhibitors

Disqualifiers: Pulmonary hypertension, Systemic hypotension, Hepatic impairment, Renal insufficiency, others

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that tadalafil will be added to usual medications for COPD. However, you cannot participate if you are currently using certain medications like nitrates, PDE-5 inhibitors, or specific drugs like rifampin and phenobarbitol.

What data supports the effectiveness of the drug tadalafil for COPD with pulmonary hypertension?

Some studies suggest that tadalafil may help improve exercise capacity and reduce shortness of breath in patients with pulmonary hypertension due to COPD, although results are mixed and more research is needed to confirm these benefits. ^{1 2 3 4 5}

Is tadalafil safe for humans, especially those with cardiovascular issues?

Tadalafil is generally considered safe and well-tolerated in humans, including those with cardiovascular conditions. It has been used for various conditions like erectile dysfunction and pulmonary hypertension, with studies showing it is well-tolerated and has a beneficial effect on the cardiovascular system. ^{1 3 5 6 7}

How does the drug tadalafil differ from other treatments for COPD with pulmonary hypertension?

Tadalafil is unique because it is a phosphodiesterase type 5 inhibitor (PDE-5i) that is being tested specifically for its effects on exercise capacity and pulmonary hemodynamics in patients with COPD and pulmonary hypertension. Unlike other treatments, tadalafil is taken orally once daily and has shown potential improvements in shortness of breath and exercise capacity, although its overall efficacy in this specific condition is still being evaluated. ^{1 2 3 4 5}

Research Team

Sharon I Rounds, MD

Principal Investigator

Providence VA Medical Center, Providence, RI

Eligibility Criteria

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.

Inclusion Criteria

Criterion Summarized: To be eligible for this study, you must have a documented condition called pulmonary hypertension and be 35-89 years old. Additionally, you need to have a score of at least 10 on a shortness of breath questionnaire and have been treated with a long-acting bronchodilator for at least 4 weeks.

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

Exclusion Criteria

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

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

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral tadalafil or placebo for 6 months to assess its effect on dyspnea and other health outcomes

6 months

Visits at 1, 2, 3, 4, 5, and 6 months (in-person or by telephone)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tadalafil (Phosphodiesterase-5 Inhibitor)

Trial Overview 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.

Participant Groups

Group I: tadalafil Active Control 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

Encapsulated placebo one or 2 encapsulated tablets po QD

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Dr. Grant Huang

VA Office of Research and Development

Acting Chief Research and Development Officer

PhD in Medical Psychology and Master of Public Health from the Uniformed Services University of Health Sciences

Dr. Erica M. Scavella

VA Office of Research and Development

Chief Medical Officer since 2022

MD from University of Massachusetts School of Medicine

Atlanta VA Medical Center

Collaborator

Trials

28

Recruited

69,700+

VA Boston Healthcare System

Collaborator

Trials

73

Recruited

971,000+

VA Eastern Colorado Health Care System

Collaborator

Trials

55

Recruited

26,200+

VA Nebraska Western Iowa Health Care System

Collaborator

Trials

9

Recruited

2,200+

Findings from Research

The TADA-PHiLD trial will evaluate the effects of tadalafil, a phosphodiesterase type 5 inhibitor, on exercise capacity and pulmonary hemodynamics in patients aged 40-85 with moderate to severe pulmonary hypertension associated with COPD, using a sample size that ensures robust results.

This study is significant as it is the first adequately powered randomized clinical trial to assess both the efficacy and safety of PDE-5 inhibitors in this patient population, focusing on key outcomes like the 6-minute walk distance and changes in pulmonary vascular resistance over a 12-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study design and rationale for investigating phosphodiesterase type 5 inhibition for the treatment of pulmonary hypertension due to chronic obstructive lung disease: the TADA-PHiLD (TADAlafil for Pulmonary Hypertension associated with chronic obstructive Lung Disease) trial. Maron, BA., Goldstein, RH., Rounds, SI., et al.[2021]

In a case study of two men with pulmonary arterial hypertension (PAH) due to chronic obstructive pulmonary disease (COPD), treatment with tadalafil led to significant improvements in pulmonary arterial pressure and right ventricular function without notable side effects.

After 4 weeks of tadalafil treatment, one patient showed an increase in exercise capacity from 10.9 mL/kg/min to 13.8 mL/kg/min, indicating enhanced physical performance alongside improved hemodynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of tadalafil for treating pulmonary arterial hypertension secondary to chronic obstructive pulmonary disease. Kim, HS., Park, JH., Park, SJ., et al.[2019]

In a study involving 42 male veterans with COPD complicated by pulmonary hypertension, tadalafil (40 mg/day) did not significantly improve the primary endpoint of 6-minute walk distance or cardiopulmonary hemodynamics compared to placebo over 12 months.

However, tadalafil treatment resulted in a clinically meaningful reduction in shortness of breath at 6 months, and it was well tolerated with no significant difference in major adverse events between the treatment and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tadalafil for veterans with chronic obstructive pulmonary disease-pulmonary hypertension: A multicenter, placebo-controlled randomized trial. Maron, BA., Choudhary, G., Goldstein, RL., et al.[2023]

In a randomized, double-blind trial involving 120 patients with moderate to severe COPD, tadalafil did not significantly improve exercise capacity or quality of life compared to placebo after 12 weeks, despite its known effects on pulmonary vasodilation.

The treatment group experienced a higher incidence of side effects, including dyspepsia (32% vs. 8% in placebo) and headaches (28% vs. 8% in placebo), indicating that while tadalafil was safe, its benefits did not outweigh the adverse effects in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tadalafil in patients with chronic obstructive pulmonary disease: a randomised, double-blind, parallel-group, placebo-controlled trial. Goudie, AR., Lipworth, BJ., Hopkinson, PJ., et al.[2015]

In a study of 1676 patients with pulmonary arterial hypertension (PAH) monitored for up to 2 years, tadalafil was found to have a favorable safety profile, with an overall adverse drug reaction (ADR) incidence of 31.2%, including common side effects like headache and diarrhea.

Tadalafil also demonstrated long-term effectiveness, with significant improvements in WHO functional classification and 6-minute walk test results over 2 years, indicating its beneficial impact on patients' functional status and exercise capacity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension: Japanese post-marketing surveillance data. Yamazaki, H., Kobayashi, N., Taketsuna, M., et al.[2018]

Tadalafil, a PDE-5 inhibitor, is effective for treating erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia, showing good tolerance in patients.

The drug is considered safe for patients with cardiovascular comorbidities and may even provide beneficial effects on cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety of tadalafil in patients with cardiovascular comorbidities]. Nikitina, IL., Gaysina, GG., Galimov, SN., et al.[2019]

Tadalafil is a safe and effective treatment option for patients with class II and III pulmonary hypertension, as recommended by the European Society of Cardiology and the European Respiratory Society, showing benefits in exercise tolerance and quality of life.

With a longer half-life allowing for a single daily dose of 40 mg, tadalafil may enhance patient adherence to treatment, making it easier for patients to manage their condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tadalafil: novel aspects of phosphodiesterase-5 inhibition in the treatment of pulmonary hypertension]. Gaudó Navarro, J., Sueiro Bendito, A.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Study design and rationale for investigating phosphodiesterase type 5 inhibition for the treatment of pulmonary hypertension due to chronic obstructive lung disease: the TADA-PHiLD (TADAlafil for Pulmonary Hypertension associated with chronic obstructive Lung Disease) trial. [2021]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Use of tadalafil for treating pulmonary arterial hypertension secondary to chronic obstructive pulmonary disease. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Tadalafil for veterans with chronic obstructive pulmonary disease-pulmonary hypertension: A multicenter, placebo-controlled randomized trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Tadalafil in patients with chronic obstructive pulmonary disease: a randomised, double-blind, parallel-group, placebo-controlled trial. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension: Japanese post-marketing surveillance data. [2018]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Safety of tadalafil in patients with cardiovascular comorbidities]. [2019]

7. Spain pubmed.ncbi.nlm.nih.gov

[Tadalafil: novel aspects of phosphodiesterase-5 inhibition in the treatment of pulmonary hypertension]. [2015]