Clinical trial NCT05567562: Anti-Platelets in Chronic Obstructive Pulmonary Disease
Official title: Dual Anti-platelet Therapy in Chronic Obstructive Pulmonary Disease Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COPD
Emphysema
Emphysema or COPD
Keywords: Platelet Dysfunction
Pulmonary Blood Vessel Injury
COPD
Emphysema
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-10-05
Enrollment: 19
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind crossover study is a Phase 2 interventional study to assess whether dual-anti platelet therapy improves pulmonary blood flow compared to placebo
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
measure: Pulmonary microvascular blood volume, CV
timeFrame: 6 weeks
Secondary outcomes:
measure: Pulmonary microvascular blood volume
timeFrame: 6 weeks
measure: Oxygen saturation
timeFrame: 6 weeks
Other outcomes:
measure: Vascular pruning on CT
timeFrame: 6 weeks
measure: Percent emphysema on CT
timeFrame: 6 weeks
measure: Functional small airways disease on CT
timeFrame: 6 weeks
measure: Lung function
timeFrame: 6 weeks
measure: Platelet activation measures
timeFrame: 6 weeks
measure: FeNO
timeFrame: 6 weeks
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Carrie L Pistenmaa, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: