Anti-Platelets in Chronic Obstructive Pulmonary Disease

COPD Clinical Trial

Official title:

Dual Anti-platelet Therapy in Chronic Obstructive Pulmonary Disease Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05567562
• Other study ID #: 2022P002327
• Secondary ID: K23HL141651
• Status: Recruiting
• Phase: Phase 2
• Start date: December 8, 2023
• Est. completion date: June 1, 2025

Study information

• Verified date: December 2023
• Source: Brigham and Women's Hospital
• Contact: Carrie L Pistenmaa, MD, MS
• Phone: 617-732-8201
• Email: arc[@]partners.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 and clopidogrel 75mg) improves pulmonary perfusion (i.e. blood flow in the lungs measured on a contrast CT scan) compared to placebo.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 75 Years

Eligibility

Inclusion Criteria - COPD Cases:

• COPD (FEV1/FVC < 0.7, FVC >= 80%), GOLD Stage I/II (FEV1 >= 50%)
• Evidence of visual emphysema (centrilobular emphysema or panlobular emphysema) on prior CT scan
• Former smoker at least 10 pack years

Inclusion Criteria - Controls:

• Normal lung function (FEV1/FVC > 0.7, FEV1 and FVC >= 80%)
• No evidence of visual emphysema on prior CT scan
• Former smoker 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 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);
• Use of supplemental oxygen at home, other than only nocturnal use;
• Regular use of an NSAID;
• Daily use of oral steroids, theophylline, roflumilast, or diuretics;
• History of organ transplant or autoimmune disease (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;
• Chest CT scan within 5 years showing significant lung mass, infiltrate (ground glass or other consolidation), or scarring/fibrosis of the lungs;
• Bullae or advanced destructive emphysema in more than 1/3 of the lungs;
• Treatment for cancer within the last 12 months;
• Known diagnosis of pulmonary hypertension;
• Known systolic heart failure (RV or LV EF < 40%);
• Use of medications for diabetes (metformin, januvia, insulin, etc);
• 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;
• Allergy to iodine contrast;
• Use of tobacco products (cigarettes, cigars or pipes) or E-cigarettes within 1 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.

Related Conditions & MeSH terms

• COPD
• Emphysema
• Emphysema or COPD
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive
• Pulmonary Emphysema

Intervention

Combination Product:
• dual anti-platelet therapy
dual anti-platelet therapy

Drug:
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Vascular pruning on CT	Distal macrovascular pruning on non-contrast inspiratory CT	6 weeks
Other	Percent emphysema on CT	Percent emphysema-950 on non-contrast inspiratory CT	6 weeks
Other	Functional small airways disease on CT	Functional small airways disease, calculated from gas trapping on non-contrast expiratory and inspiratory CT	6 weeks
Other	Lung function	Spirometry measures of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC	6 weeks
Other	Plasma biomarkers	Biomarkers related to endothelial activation (sICAM-1, sVCAM-1, sP-selectin, sE-selectin, vWF), angiogenesis (VEGF, TIMP-1 and PAI-1) and inflammation (WBC, CRP, IL-6, TNF-a, myeloperoxidase).	6 weeks
Other	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. Also urine 11d-TXB2, plasma TXB2 and aspirin-triggered lipoxin A4	6 weeks
Other	FeNO	Fraction of exhaled nitric oxide	6 weeks
Primary	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	6 weeks
Secondary	Pulmonary microvascular blood volume	Pulmonary microvascular blood volume on dual energy CT scan, comparing on dual antiplatelet therapy to placebo	6 weeks
Secondary	Pulmonary microvascular blood flow, CV	Coefficient of variation (CV) of pulmonary microvascular blood flow on dual energy CT scan, comparing on dual antiplatelet therapy to placebo	6 weeks
Secondary	Pulmonary microvascular blood flow	Pulmonary microvascular blood flow on dual energy CT scan, comparing on dual antiplatelet therapy to placebo	6 weeks
Secondary	Diffusing capacity	DLCO	6 weeks
Secondary	Oxygen saturation	Resting oxygen saturation	6 weeks