Trial to Determine Effective Aspirin Dose in COPD

Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age40-80
SponsorJohns Hopkins University

About this trial

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States. Current treatments for COPD focus on inhaler therapies that do not address manifestations of the disease on other organ systems. Platelets, which are small blood cells that typically help with clotting, are also involved in generalized inflammation and dysfunctionality of immune cells when these cells become activated. Activated platelets have long been known to play a role in the development of cardiovascular disease. However, there is recent evidence that activated platelets may be involved in worse respiratory symptoms in COPD independent of cardiovascular disease. Individuals with COPD who are taking aspirin, which is an antiplatelet agent that blocks activation of platelets, have been shown to have improved respiratory symptoms, fewer COPD flares, and lower mortality. The investigators' ultimate goal is to study whether aspirin use improves respiratory symptoms independent of cardiovascular disease. The investigators are conducting the current pilot trial to determine the optimal dose of aspirin that blocks platelet activation in this population and investigate whether there are any blood or urine tests that can help with understanding response to therapy. The results will inform the design of a larger trial investigating clinical outcomes. The investigators hypothesize that daily low-dose aspirin will not be sufficient to adequately suppress platelet activation and that an aspirin dose of at least 162mg daily will be necessary.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥40 years

Former smoker

At least 10 pack-year smoking history

Post-bronchodilator ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) < 0.7

Disqualifiers

History of myocardial infarction, percutaneous coronary intervention, or stroke

Currently taking antiplatelet therapy (other than aspirin 81mg) or anticoagulant medication

Contraindication to aspirin (including low platelet count, hematocrit <25%, known aspirin-exacerbated respiratory disease, bleeding disorder, history of bleeding or gastrointestinal (GI) ulcer, coagulopathy, or major surgery within 6 weeks before randomization)

Oral corticosteroids within the past 6 weeks

Trial design

Design model

Sequential

Treatments tested in this trial

  • Aspirin 81mg

    Drug

    Aspirin 81mg once daily

  • Aspirin 162 mg

    Drug

    Aspirin 162 mg once daily

  • Aspirin 325mg

    Drug

    Aspirin 325mg once daily

Treatment groups

48 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Sequence 1Experimental treatment 3 interventions
Group B: Sequence 2Experimental treatment 3 interventions
Group C: Sequence 3Experimental treatment 3 interventions
Group D: Sequence 4Experimental treatment 3 interventions
Group E: Sequence 5Experimental treatment 3 interventions
Group F: Sequence 6Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Change in urinary 11-dehydro-thromboxane B2 level

Urine 11-dehydro-thromboxane B2 level (pg/mg Creatinine) - a urinary metabolite of thromboxane A2.

Time frame
Baseline, week 2, week 6, week 10
2

Change in serum thromboxane B2 level

Serum thromboxane B2

Time frame
Baseline, week 2, week 6, week 10

Secondary outcomes

1

Change in proportion of platelets displaying CD62P

Proportion of platelets displaying CD62P (activated platelets) following stimulation with U46619, a thromboxane A2 agonist.

Time frame
Baseline, 2 weeks, 6 weeks, 10 weeks
2

Change in proportion of platelets displaying CD63

Proportion of platelets displaying CD63 (activated platelets) following stimulation with U46619, a thromboxane A2 agonist.

Time frame
Baseline, 2 weeks, 6 weeks, 10 weeks
3

Change in proportion of platelets displaying CD154

Proportion of platelets displaying CD154 (activated platelets) following stimulation with U46619, a thromboxane A2 agonist

Time frame
Baseline, 2 weeks, 6 weeks, 10 weeks
4

Change in proportion of platelets displaying PAC1

Proportion of platelets displaying PAC1 (activated platelets) following stimulation with U46619, a thromboxane A2 agonist

Time frame
Baseline, 2 weeks, 6 weeks, 10 weeks

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Johns Hopkins University

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator