Anti-Platelets in Chronic Obstructive Pulmonary Disease

Mass General Brigham

Status and phase: Completed; Phase 2

Conditions: Emphysema; COPD; Emphysema or COPD

Treatments: Combination Product: dual anti-platelet therapy; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05567562

2022P002327

K23HL141651 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 50 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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19 participants in 4 patient groups, including a placebo group

COPD Cases: Dual antiplatelet therapy first, then placebo

Experimental group

Description:

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

Treatment:

Drug: Placebo

Combination Product: dual anti-platelet therapy

COPD Cases: Placebo first, then dual antiplatelet therapy

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Combination Product: dual anti-platelet therapy

Controls: Dual antiplatelet therapy first, then placebo

Active Comparator group

Description:

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

Treatment:

Drug: Placebo

Combination Product: dual anti-platelet therapy

Controls: Placebo first, then dual antiplatelet therapy

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Combination Product: dual anti-platelet therapy