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Anti-Platelets in Chronic Obstructive Pulmonary Disease

Primary Purpose

COPD, Emphysema, Emphysema or COPD

Status

Not yet recruiting

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

dual anti-platelet therapy

Placebo

About this trial

This is an interventional other trial for COPD focused on measuring Platelet Dysfunction, Pulmonary Blood Vessel Injury, COPD, Emphysema

Eligibility Criteria

50 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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 or clopidogrel;
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;
Daily use of oral steroids, theophylline, roflumilast, or diuretics;
History of major lung surgery or lung transplant;
Chest CT scan showing significant lung mass, infiltrate (ground glass or other consolidation), or scarring/fibrosis of the lungs;
Treatment for cancer within the last 12 months;
Pulmonary hypertension;
BMI > 30;
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 or E-cigarettes within 1 year;
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 (spirometry exclusion criteria).

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Active Comparator

Placebo Comparator

Arm Label

COPD Cases: Dual antiplatelet therapy first, then placebo

COPD Cases: Placebo first, then dual antiplatelet therapy

Controls: Dual antiplatelet therapy first, then placebo

Controls: Placebo first, then dual antiplatelet therapy

Arm 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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Pulmonary microvascular blood volume

Pulmonary microvascular blood volume on dual energy CT scan, comparing on dual antiplatelet therapy to placebo

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

Pulmonary microvascular blood flow

Pulmonary microvascular blood flow on dual energy CT scan, comparing on dual antiplatelet therapy to placebo

Diffusing capacity

DLCO

Oxygen saturation

Resting oxygen saturation

Full Information

NCT ID

NCT05567562

First Posted

October 3, 2022

Last Updated

March 15, 2023

Sponsor

Brigham and Women's Hospital

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT05567562

Brief Title

Anti-Platelets in Chronic Obstructive Pulmonary Disease

Official Title

Dual Anti-platelet Therapy in Chronic Obstructive Pulmonary Disease Study

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

April 24, 2023 (Anticipated)

Primary Completion Date

May 1, 2024 (Anticipated)

Study Completion Date

August 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Brigham and Women's Hospital

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a 6 week crossover study in 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COPD, Emphysema, Emphysema or COPD

Keywords

Platelet Dysfunction, Pulmonary Blood Vessel Injury, COPD, Emphysema

7. Study Design

Primary Purpose

Other

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

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

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

All participants, investigators and care providers will be blinded as to dual-anti platelet therapy or placebo treatment

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

COPD Cases: Dual antiplatelet therapy first, then placebo

Arm Type

Experimental

Arm 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

Arm Title

COPD Cases: Placebo first, then dual antiplatelet therapy

Arm Type

Placebo Comparator

Arm 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

Arm Title

Controls: Dual antiplatelet therapy first, then placebo

Arm Type

Active Comparator

Arm 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

Arm Title

Controls: Placebo first, then dual antiplatelet therapy

Arm Type

Placebo Comparator

Arm 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

Intervention Type

Combination Product

Intervention Name(s)

dual anti-platelet therapy

Other Intervention Name(s)

aspirin 81mg EC tab, clopidogrel 75mg tab

Intervention Description

dual anti-platelet therapy

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

Pulmonary microvascular blood volume, CV

Description

Coefficient of variation (CV) of pulmonary microvascular blood volume on dual energy CT scan, comparing on dual antiplatelet therapy to placebo

Time Frame

6 weeks

Secondary Outcome Measure Information:

Title

Pulmonary microvascular blood volume

Description

Pulmonary microvascular blood volume on dual energy CT scan, comparing on dual antiplatelet therapy to placebo

Time Frame

6 weeks

Title

Pulmonary microvascular blood flow, CV

Description

Coefficient of variation (CV) of pulmonary microvascular blood flow on dual energy CT scan, comparing on dual antiplatelet therapy to placebo

Time Frame

6 weeks

Title

Pulmonary microvascular blood flow

Description

Pulmonary microvascular blood flow on dual energy CT scan, comparing on dual antiplatelet therapy to placebo

Time Frame

6 weeks

Title

Diffusing capacity

Description

DLCO

Time Frame

6 weeks

Title

Oxygen saturation

Description

Resting oxygen saturation

Time Frame

6 weeks

Other Pre-specified Outcome Measures:

Title

Vascular pruning on CT

Description

Distal macrovascular pruning on non-contrast inspiratory CT

Time Frame

6 weeks

Title

Percent emphysema on CT

Description

Percent emphysema-950 on non-contrast inspiratory CT

Time Frame

6 weeks

Title

Functional small airways disease on CT

Description

Functional small airways disease, calculated from gas trapping on non-contrast expiratory and inspiratory CT

Time Frame

6 weeks

Title

Lung function

Description

Spirometry measures of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC

Time Frame

6 weeks

Title

Plasma biomarkers

Description

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).

Time Frame

6 weeks

Title

Platelet activation measures

Description

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

Time Frame

6 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 or clopidogrel; 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; Daily use of oral steroids, theophylline, roflumilast, or diuretics; History of major lung surgery or lung transplant; Chest CT scan showing significant lung mass, infiltrate (ground glass or other consolidation), or scarring/fibrosis of the lungs; Treatment for cancer within the last 12 months; Pulmonary hypertension; BMI > 30; 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 or E-cigarettes within 1 year; 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 (spirometry exclusion criteria).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Carrie L Pistenmaa, MD, MS

Phone

617-525-9805

cpistenmaa@bwh.harvard.edu

First Name & Middle Initial & Last Name or Official Title & Degree

George Washko, MD, MS

Phone

617-525-8029

gwashko@bwh.harvard.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Carrie L Pistenmaa, MD, MS

Organizational Affiliation

Brigham and Women's Hospital

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

This is a small single-center study, we do not plan to share participant level data

Learn more about this trial

Anti-Platelets in Chronic Obstructive Pulmonary Disease

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