Tadalafil for COPD with Pulmonary Hypertension

(BETTER COPD-PH Trial)

Recruiting at 4 trial locations

Overseen By Ronald H Goldstein, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 6 months

126 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether tadalafil (also known as Cialis), typically used for other conditions, can improve breathing and quality of life in Veterans with COPD and pulmonary hypertension. Participants will receive either tadalafil or a placebo (a pill with no active ingredient) to assess improvements in symptoms and daily activities. Veterans with COPD who frequently experience breathing difficulties might be suitable for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important medical research.

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.

Is there any evidence suggesting that tadalafil is likely to be safe for humans?

Research has shown that tadalafil has been tested in patients with conditions similar to those in this trial, such as high blood pressure in the lungs caused by COPD. Studies have found that tadalafil was generally safe and well-tolerated in these patients. For instance, one study found that tadalafil improved patients' ability to function without major safety issues. However, another study noted that it might not be suitable for those with moderate to severe COPD and mild lung high blood pressure. These findings suggest that while tadalafil has been safe for some, it may not be right for everyone with COPD and lung high blood pressure. Participants should consider these findings and discuss them with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for COPD?

Tadalafil is unique because it's being explored for use in COPD patients with pulmonary hypertension, a condition where treatment options are limited. Most current treatments for pulmonary hypertension in COPD focus on symptom management with bronchodilators or oxygen therapy. However, Tadalafil, known for treating erectile dysfunction and pulmonary arterial hypertension, works by relaxing blood vessels and improving blood flow, which could directly target the underlying issues in the lungs. Researchers are excited about this treatment because it has the potential to address pulmonary hypertension in COPD more effectively by enhancing blood flow, which could lead to better breathing and overall health outcomes for patients.

What evidence suggests that tadalafil might be an effective treatment for COPD with pulmonary hypertension?

This trial will compare tadalafil with a placebo to evaluate its effects on Pulmonary Hypertension in patients with COPD. Research has shown that tadalafil might help with Pulmonary Hypertension, which is high blood pressure in the lungs. In some individuals with this condition, it increased walking distance and reduced lung pressure. However, other studies found no significant improvement in exercise ability for people with COPD. Despite these mixed results, some patients reported feeling less short of breath, suggesting possible benefits. It's important to note that while tadalafil might help with lung pressure, its effects can vary among individuals. ^{4 6 7 8 9}

Who Is on the Research Team?

Sharon I Rounds, MD

Principal Investigator

Providence VA Medical Center, Providence, RI

Are You a Good Fit for This Trial?

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 oxygen levels fall below 90% even with extra oxygen.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Tadalafil

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.

How Is the Trial Designed?

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+

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9053004/

Tadalafil for veterans with chronic obstructive pulmonary ... In this study, no significant change in exercise capacity measured using 6‐MWD was observed in the tadalafil group compared to placebo. These findings were ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01862536?term=AREA%5BConditionSearch%5D(%22Lung%20Disease%22)%20AND%20AREA%5BInterventionSearch%5D(%22Tadalafil%22)&rank=4

Tadalafil for Pulmonary Hypertension Due to Chronic Lung ... Results from this study are expected to define the potential use of PDE-5 inhibitors in COPD-induced pulmonary hypertension.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12479374/

Study Design and Rationale for The Breathe Easier With ... In WHO group 1 patients, tadalafil was effective in improving 6MWD and time to clinical worsening, as well as mean pulmonary artery pressure ...

4. thelancet.com thelancet.com/journals/lanres/article/PIIS2213-2600(14)70013-X/fulltext

Tadalafil in patients with chronic obstructive pulmonary ... We aimed to assess the effects of tadalafil—a PDE5 inhibitor—on exercise capacity and quality of life in patients with COPD and mild pulmonary ...

5. pvrinstitute.org pvrinstitute.org/learning-hub/material/study-design-and-rationale-breathe-easier-tadalafil-therapy-exercise-related

Study Design and Rationale for The Breathe Easier With ... While tadalafil did not change 6MWD at 12 months, the treatment group experienced clinically meaningful improvements in patient-reported dyspnea ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2687595/

Use of Tadalafil for Treating Pulmonary Arterial ... Tadalafil showed promising results for treating pulmonary arterial hypertension secondary to COPD. It was safe and efficacious in improving the functional ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4070834/

the TADA-PHiLD (TADAlafil for Pulmonary Hypertension ... Changes in systemic blood pressure and/or oxyhemoglobin saturation (Sao2) at rest and during exercise will function as safety outcome measures. TADA-PHiLD ( ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05844462

Tadalafil for Severe Pulmonary Hypertension Due to ... The main objective to this randomized controlled trial (16 weeks) is to evaluate the efficacy and safety of an oral PDE5i, tadalafil, in patients with severe PH ...

9. trialx.com trialx.com/clinical-trials/listings/287127/tadalafil-for-severe-pulmonary-hypertension-due-to-chronic-obstructive-pulmonary-disease/

Tadalafil for Severe Pulmonary Hypertension Due to ... Data are lacking regarding the benefit/risk ratio of these treatments in the context of severe PH due to COPD. The main objective to this ...