Anti-Platelets in Chronic Obstructive Pulmonary Disease

Dual Anti-platelet Therapy in Chronic Obstructive Pulmonary Disease Study

This is a 6 week crossover study in current and former smokers with and without COPD to evaluate whether 2 weeks of dual antiplatelet therapy (aspirin 81mg and clopidogrel 75mg) improves pulmonary perfusion (i.e. blood flow in the lungs measured on a contrast CT scan) compared to placebo.

Study Overview

• Status: Completed
• Conditions: Emphysema; COPD; Emphysema or COPD
• Intervention / Treatment: Drug: Placebo; Combination product: dual anti-platelet therapy

Detailed Description

This is a single-center Phase IIa randomized double-blind crossover study in smokers with and without chronic obstructive pulmonary disease (COPD) to test whether dual antiplatelet therapy (aspirin 81mg and clopidogrel 75mg) improves pulmonary perfusion (i.e. blood flow in the lungs) compared to placebo.

We will enroll 30 subjects (20 with COPD, 10 without) who will each take part for 6 weeks. Participants and researchers will be blinded, they will not know which medications they are on first. Each participant will be asked to take aspirin and clopidogrel together for 2 weeks and also matching placebos for 2 weeks, with a 2 week washout period in between. Pulmonary blood flow will be evaluated with a contrast-enhanced CT scan of the chest two times over the 6 week study.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria - COPD Cases:

• COPD (FEV1/FVC < 0.7, FVC >= LLN), GOLD Stage I/II/III (FEV1 >= 40%)
• Current or former smoker of at least 10 pack years

Inclusion Criteria - Controls:

• Normal lung function (FEV1/FVC >= 0.7, FEV1 and FVC >= LLN)
• Current or former smoker of at least 10 pack years

Exclusion Criteria:

• Platelet count < 150,000/dL or self-report of a bleeding disorder;
• Regular use of aspirin, clopidogrel or another antiplatelet medication;
• Allergy to aspirin, clopidogrel, albuterol or iodine/IV contrast;
• BMI > 35;
• History of intracranial hemorrhage, severe GI bleed or other life-threatening bleed;
• Use of blood thinner (e.g. warfarin, lovenox or novel oral anti-coagulants);
• Continuous use of supplemental oxygen at home;
• Regular use of an NSAID;
• Daily use of oral steroids, theophylline, roflumilast, or loop diuretics;
• History of organ transplant or autoimmune disease on systemic therapy (rheumatoid arthritis, lupus);
• Use of a biologic medication with regular injections;
• Other current lung disease (interstitial lung disease, idiopathic pulmonary fibrosis, asthma);
• IV drug use within the last year;
• History of lung surgery to remove part of the lung;
• Known bullae or advanced destructive emphysema in more than 1/3 of the lungs;
• Treatment for cancer (systemic therapy or surgical/radiation within the thorax) in the last 12 months;
• Known diagnosis of pulmonary hypertension;
• Known systolic heart failure (RV or LV EF < 40%);
• Acute or chronic renal insufficiency (estimated glomerular filtration rate [GFR] <60 mL/min/1.73 m2 or self-report). GFR will be calculated using the CKD-EPI equation;
• Current or planned pregnancy in the next year;
• Regular marijuana smoking;
• Exacerbation of respiratory symptoms within the previous 6 weeks, such as that requiring hospitalization, oral prednisone or antibiotics to control symptoms, or longer and not yet returned to baseline; and
• Chest, abdominal or eye surgery, or a heart attack or stroke, within the last 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: COPD Cases: Dual antiplatelet therapy first, then placebo; 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	Drug: Placebo; Placebo; Combination product: dual anti-platelet therapy; dual anti-platelet therapy; Other Names: aspirin 81mg EC tab; clopidogrel 75mg tab
Placebo Comparator: COPD Cases: Placebo first, then dual antiplatelet therapy; 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	Drug: Placebo; Placebo; Combination product: dual anti-platelet therapy; dual anti-platelet therapy; Other Names: aspirin 81mg EC tab; clopidogrel 75mg tab
Active Comparator: Controls: Dual antiplatelet therapy first, then placebo; 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	Drug: Placebo; Placebo; Combination product: dual anti-platelet therapy; dual anti-platelet therapy; Other Names: aspirin 81mg EC tab; clopidogrel 75mg tab
Placebo Comparator: Controls: Placebo first, then dual antiplatelet therapy; 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	Drug: Placebo; Placebo; Combination product: dual anti-platelet therapy; dual anti-platelet therapy; Other Names: aspirin 81mg EC tab; clopidogrel 75mg tab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Microvascular Blood Volume, CV	Coefficient of variation (CV) of pulmonary microvascular blood volume on dual energy CT scan, comparing on dual antiplatelet therapy to placebo	After 2 weeks of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Microvascular Blood Volume	Pulmonary microvascular blood volume on dual energy CT scan, comparing on dual antiplatelet therapy to placebo	After 2 weeks of therapy
Oxygen Saturation	Resting oxygen saturation	After 2 weeks of therapy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Small Vessel Fraction on CT	Small vessel volume (vessels <5mm2 in CSA) as a percent of total lung volume, measured on non-contrast inspiratory CT	After 2 weeks of therapy
Percent Emphysema on CT	Percent of lung below -950HU on non-contrast inspiratory CT	After 2 weeks of therapy
Air Trapping on Expiratory CT	Percentage of lung volume with attenuation <-856HU on expiratory CT	After 2 weeks of therapy
Post-BD FEV1	Forced expiratory volume in 1 second, post-bronchodilator	After 2 weeks of therapy
Platelet Activation Measures	Platelet activation measures by flow cytometry: circulating monocyte-platelet aggregates (unstimulated), activated GPIIb/IIIa receptor, unstimulated, and stimulated by low and high dose arachidonic acid and adenosine diphosphate, and P-selectin on the platelet surface, unstimulated, and stimulated by low and high dose arachidonic acid and adenosine diphosphate.	After 2 weeks of therapy
FeNO	Fraction of exhaled nitric oxide	After 2 weeks of therapy

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Carrie L Pistenmaa, MD, MS, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2024
• Primary Completion (Actual): February 28, 2025
• Study Completion (Actual): February 28, 2025

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: October 3, 2022
• First Posted (Actual): October 5, 2022

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: COPD; Emphysema; Platelet Dysfunction; Pulmonary Blood Vessel Injury
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Emphysema; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Drug Therapy; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Thiophenes; Salicylates; Hydroxybenzoates; Ticlopidine; Thienopyridines; Drug Therapy, Combination; Clopidogrel; Aspirin; Dual Anti-Platelet Therapy
• Other Study ID Numbers: 2022P002327; K23HL141651 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is a small single-center study, we do not plan to share participant level data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No