Antiplatelet Therapy for COPD

Overseen By Maria A Cinelli

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must not be taking: Antiplatelets, Blood thinners, NSAIDs, Steroids

Disqualifiers: Bleeding disorders, Obesity, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of two medications, aspirin and clopidogrel (known as Dual Anti-Platelet Therapy), can improve blood flow in the lungs for individuals who smoke or used to smoke, including some with chronic obstructive pulmonary disease (COPD). Participants will take the medications and a placebo at different times over a short-term, six-week period to compare the effects. The trial seeks individuals who have smoked for at least 10 years, with or without COPD, and who do not regularly use certain blood-related medications or have a history of severe bleeding issues. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as aspirin, clopidogrel, other antiplatelet medications, blood thinners, NSAIDs, oral steroids, and some other specific drugs. If you are on any of these, you may need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking aspirin and clopidogrel together, known as dual antiplatelet therapy, is usually safe for most people. This combination can significantly reduce the risk of heart attacks and death in individuals with heart problems. However, it may also increase the risk of bleeding, as both medications prevent blood clots, potentially leading to bleeding issues.

Some studies have found that discontinuing this therapy after a certain period might reduce long-term bleeding problems. While the treatment is effective, monitoring health closely is crucial. Prospective trial participants should consult a healthcare provider to understand the benefits and risks. ^{1 2 3 4 5}

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

Researchers are excited about using dual antiplatelet therapy for COPD because it targets the underlying inflammation and clotting issues that can worsen lung function in COPD patients. Unlike standard COPD treatments, which typically focus on bronchodilators and steroids to open airways and reduce inflammation, this therapy uses aspirin and clopidogrel to prevent blood platelets from clumping. This novel approach could potentially improve blood flow and oxygen delivery in the lungs, offering a new avenue for managing COPD symptoms. Additionally, the treatment is administered in short, two-week bursts, which might lead to quicker results compared to the longer treatment periods required by current options.

What evidence suggests that dual antiplatelet therapy could be effective for COPD?

Research has shown that using two medications together, aspirin and clopidogrel, may improve lung health in people with chronic obstructive pulmonary disease (COPD). In earlier studies, patients who took this combination experienced better health outcomes, suggesting it might enhance lung function. This trial will evaluate the effects of dual antiplatelet therapy, consisting of aspirin and clopidogrel, on lung health in COPD patients. Participants will receive either dual antiplatelet therapy followed by a placebo or a placebo followed by dual antiplatelet therapy. This treatment likely works by improving blood flow in the lungs, which can be especially beneficial for those with COPD. While these findings are encouraging, more research is needed to fully understand the benefits. Overall, this therapy could be a useful option for improving lung blood flow in COPD patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Carrie Pistenmaa, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for former smokers, with or without Chronic Obstructive Pulmonary Disease (COPD), who have a history of significant smoking. Participants must show signs of emphysema on a CT scan and meet specific lung function criteria (FEV1/FVC < 0.7 and FVC >= 80%). Those with normal lung function but no visual emphysema are also eligible.

Inclusion Criteria

Your previous CT scan shows signs of visual emphysema in your lungs.

I have mild to moderate COPD with specific lung function levels.

Your previous CT scan doesn't show signs of visual emphysema.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dual antiplatelet therapy (aspirin 81mg and clopidogrel 75mg) for 2 weeks, followed by a 2-week washout period, and then 2 weeks of placebo, or vice versa

6 weeks

2 visits (in-person) for CT scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dual Anti-Platelet Therapy
• Placebo

Trial Overview The study is testing if dual anti-platelet therapy (aspirin and clopidogrel) over two weeks can improve blood flow in the lungs compared to a placebo. This six-week crossover study involves participants switching between the treatment and placebo.

How Is the Trial Designed?

Group I: COPD Cases: Dual antiplatelet therapy first, then placebo Experimental Treatment 2 Interventions

Dual antiplatelet therapy (aspirin 81mg and clopidogrel 75mg) will be given for 2 weeks, followed by 2 weeks without intervention, then 2 weeks of placebo

Group II: Controls: Dual antiplatelet therapy first, then placebo Active Control 2 Interventions

Dual antiplatelet therapy (aspirin 81mg and clopidogrel 75mg) will be given for 2 weeks, followed by 2 weeks without intervention, then 2 weeks of placebo

Group III: COPD Cases: Placebo first, then dual antiplatelet therapy Placebo Group 2 Interventions

Placebos for each therapy (2 pills) will be given for 2 weeks, followed by 2 weeks without intervention, then 2 weeks of dual antiplatelet therapy

Group IV: Controls: Placebo first, then dual antiplatelet therapy Placebo Group 2 Interventions

Placebos for each therapy (2 pills) will be given for 2 weeks, followed by 2 weeks without intervention, then 2 weeks of dual antiplatelet therapy

Dual Anti-Platelet Therapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as DAPT for:

• Prevention of thrombotic events after percutaneous coronary intervention (PCI) with drug-eluting stents (DES)
• Acute coronary syndrome (ACS)
• Chronic coronary syndrome

Approved in United States as DAPT for:

• Prevention of thrombotic events after PCI with DES
• ACS
• Secondary prevention of cardiovascular events

Approved in Canada as DAPT for:

• Prevention of thrombotic events after PCI with DES
• ACS
• Chronic coronary syndrome

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study of 40 patients on dual-antiplatelet therapy (DAPT), significant variability in individual responses to antiplatelet therapy was observed within the first week after hospital discharge, particularly in platelet reactivity measures.

While responses stabilized after the first week, the findings suggest that relying on a single platelet function test before discharge may not accurately predict long-term responses to therapy, indicating a need for more tailored approaches in monitoring and adjusting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does the response to aspirin and clopidogrel vary over 6 months in patients with ischemic heart disease? Khanna, V., Mikael, R., Thayalasamy, K., et al.[2023]

Dual antiplatelet therapy (DAPT) using clopidogrel and aspirin is recommended for preventing recurrent ischemic events in patients with coronary heart disease and stroke, highlighting its efficacy in reducing complications.

However, clopidogrel has limitations, such as variable patient response and delayed recovery of platelet function, which may necessitate the exploration of newer antiplatelet agents like prasugrel, ticagrelor, and PAR-1 inhibitors for improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antiplatelet drugs]. Nishikawa, M.[2018]

In a study of 2,993 patients, those undergoing complex percutaneous coronary interventions (PCI) had a higher risk of major adverse cardiac and cerebrovascular events (MACCE) compared to those without complex PCIs, indicating that complexity in PCI procedures is associated with increased risk.

However, P2Y12 inhibitor monotherapy, primarily clopidogrel, after 3 months of dual antiplatelet therapy (DAPT) did not lead to an increase in ischemic events for patients with complex PCIs, suggesting it is a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

P2Y12 inhibitor monotherapy in complex percutaneous coronary intervention: A post-hoc analysis of SMART-CHOICE randomized clinical trial. Roh, JW., Hahn, JY., Oh, JH., et al.[2022]

Dual antiplatelet therapy (DAPT) with aspirin and ticagrelor is effective in treating acute coronary syndromes, but there is still a risk of ischemic events and bleeding complications, prompting research into alternative therapies.

A new subcutaneously administered P2Y12 inhibitor, selatogrel, has demonstrated rapid and consistent antiplatelet effects in a phase 2 study, suggesting it may be a promising option for patients requiring antiplatelet therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel approaches to P2Y12 inhibition and aspirin dosing. Parker, WAE., Storey, RF.[2021]

The SMART-CHOICE trial is a large-scale study involving 3000 patients that aims to determine if P2Y12 inhibitor monotherapy can effectively reduce thrombotic events while lowering the risk of bleeding compared to dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor after 3 months of treatment.

The primary outcome will assess the safety and efficacy of the treatment strategies by measuring all-cause death, myocardial infarction, and cerebrovascular events over 12 months, providing valuable insights into the optimal antiplatelet therapy following percutaneous coronary intervention with drug-eluting stents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of the comparison between a P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients undergoing implantation of coronary drug-eluting stents (SMART-CHOICE): A prospective multicenter randomized trial. Song, YB., Oh, SK., Oh, JH., et al.[2019]

Dual anti-platelet therapy, specifically the combination of aspirin and clopidogrel, significantly reduces the risk of recurrent heart attacks and death in patients with acute coronary syndromes, as shown in multiple randomized control trials.

Despite the benefits of this combination, many patients still face ischemic events due to the limitations of aspirin and clopidogrel, prompting the development of new anti-platelet agents that are currently being evaluated in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Platelet Therapy for Acute Coronary Syndrome: A Review of Currently Available Agents and What the Future Holds. Syed, FA., Bett, JH., Walters, DL.[2019]

In a study analyzing platelet reactivity in post-PCI patients, the VASP flow cytometric assay showed a 100% response rate in patients treated with prasugrel, compared to only 62% to 73% in those treated with clopidogrel, highlighting the variability in response to clopidogrel.

The study suggests that using the VASP-phosphorylation assay could be an effective method for monitoring and personalizing dual antiplatelet therapy, as only 7% of patients with therapeutic VASP-PRI values experienced major adverse cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring the efficacy of ADP inhibitor treatment in patients with acute STEMI post-PCI by VASP-P flow cytometry assay. Fedor, M., Samoš, M., Šimonová, R., et al.[2018]

Dual antiplatelet therapy (DAPT), which includes aspirin and a P2Y12 inhibitor, remains the standard treatment for patients undergoing percutaneous coronary interventions (PCI) to reduce thrombotic events.

Recent randomized controlled trials have focused on finding less aggressive antithrombotic regimens that balance the risks of ischemic events and bleeding, leading to updates in clinical practice guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiplatelet therapy in percutaneous coronary intervention: latest evidence from randomized controlled trials. Galli, M., Angiolillo, DJ.[2023]

The optimal duration of dual antiplatelet therapy (DAPT) for coronary artery disease (CAD) patients should be tailored based on individual thrombotic risk and bleeding risk, considering factors like the type of stent used and the patient's medical history.

Current guidelines provide a framework for clinicians, but special populations such as elderly patients or those with diabetes may require more nuanced decision-making due to the variability in study results regarding DAPT duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of Dual Antiplatelet Therapy After Coronary Stenting. Siasos, G., Mourouzis, K., Oikonomou, E., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11242589/

Clinical Outcomes of Aspirin and Clopidogrel among ... (1) Background: Aspirin and clopidogrel have been found helpful in improving clinical outcomes among patients with chronic obstructive lung ...

2. trialx.com trialx.com/clinical-trials/listings/269753/anti-platelets-in-chronic-obstructive-pulmonary-disease/

Anti-Platelets in Chronic Obstructive Pulmonary Disease This is a 6 week crossover study in former smokers with and without COPD to evaluate whether 2 weeks of dual antiplatelet therapy (aspirin 81mg ...

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.122.027055

Long‐Term Outcomes and Duration of Dual Antiplatelet ... Stopping DAPT after 9 months is associated with lower long‐term risks of adverse ischemic and bleeding events and supports recent guidelines of shorter ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5988059/

Antiplatelet therapy in the primary prevention of ... The primary goal of this trial is to investigate if treatment with antiplatelet therapy will produce the required response in platelet function.

5. jacc.org jacc.org/doi/10.1016/j.jacc.2023.10.013

Clopidogrel vs Aspirin Monotherapy Beyond 1 Year After ... It remains unclear whether clopidogrel is better suited than aspirin as the long-term antiplatelet monotherapy following dual antiplatelet therapy (DAPT) after ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa060989

Clopidogrel and Aspirin versus Aspirin Alone for ... Data on mortality rates suggest that dual antiplatelet therapy should not be used in patients without a history of established vascular disease. Notes. This ...

7. withpower.com withpower.com/trial/phase-2-emphysema-10-2022-43fd8

Antiplatelet Therapy for COPD · Info for Participants Dual anti-platelet therapy, specifically the combination of aspirin and clopidogrel, significantly reduces the risk of recurrent heart attacks and death in ...