Trial to Determine Effective Aspirin Dose in COPD
Primary Purpose
Pulmonary Disease, Chronic Obstructive
Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Aspirin 81mg
Aspirin 162 mg
Aspirin 325mg
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- History of myocardial infarction, percutaneous coronary intervention, or stroke
- Presence of coronary artery calcification on computed tomography (CT) scan by visual assessment
- Currently taking antiplatelet therapy 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
- Currently taking immunosuppressant medication
- Active malignancy (other than non-melanoma skin cancer)
- Uncontrolled hypertension
- Pregnant or planning pregnancy in the next year
- Plans to move residence away from the immediate area within the next 3 months
Sites / Locations
- Johns Hopkins Bayview Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Sequence 1
Sequence 2
Sequence 3
Sequence 4
Sequence 5
Sequence 6
Arm Description
Week 1-2: aspirin 81mg Week 5-6: aspirin 162mg Week 9-10: aspirin 325mg
Week 1-2: aspirin 162mg Week 5-6: aspirin 81mg Week 9-10: aspirin 325mg
Week 1-2: aspirin 325mg Week 5-6: aspirin 81mg Week 9-10: aspirin 162mg
Week 1-2: aspirin 325mg Week 5-6: aspirin 162mg Week 9-10: aspirin 81mg
Week 1-2: aspirin 162mg Week 5-6: aspirin 325mg Week 9-10: aspirin 81mg
Week 1-2: aspirin 81mg Week 5-6: aspirin 325mg Week 9-10: aspirin 162mg
Outcomes
Primary Outcome Measures
Change in urinary 11-dehydro-thromboxane B2 level
Urine 11-dehydro-thromboxane B2 level (pg/mg Creatinine) - a urinary metabolite of thromboxane A2.
Change in serum thromboxane B2 level
Serum thromboxane B2
Secondary Outcome Measures
Change in proportion of platelets displaying CD62P
Proportion of platelets displaying CD62P (activated platelets) following stimulation with U46619, a thromboxane A2 agonist.
Change in proportion of platelets displaying CD63
Proportion of platelets displaying CD63 (activated platelets) following stimulation with U46619, a thromboxane A2 agonist.
Change in proportion of platelets displaying CD154
Proportion of platelets displaying CD154 (activated platelets) following stimulation with U46619, a thromboxane A2 agonist
Change in proportion of platelets displaying PAC1
Proportion of platelets displaying PAC1 (activated platelets) following stimulation with U46619, a thromboxane A2 agonist
Full Information
NCT ID
NCT05265299
First Posted
February 22, 2022
Last Updated
May 16, 2023
Sponsor
Johns Hopkins University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT05265299
Brief Title
Trial to Determine Effective Aspirin Dose in COPD
Official Title
Randomized Trial to Determine Effective Aspirin Dose in COPD
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 16, 2023 (Actual)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
The trial will enroll individuals with chronic obstructive pulmonary disease (COPD). The primary design will be a randomized double-blind 6-sequence, 3-period, 3-treatment sequential crossover trial for which the investigators will randomize participants to receive 81mg, 162mg, and 325mg aspirin in one of six pre-specified sequences with a 14-day washout period between doses. Participants will have three follow-up visits after randomization.
Individuals who agree to participate in the clinical trial will be randomized to one of six treatment sequences using a computer algorithm at the baseline study visit. Study drug will be provided by the Johns Hopkins Research Pharmacy and participants instructed to take one pill once per day at the same time. All study drug doses will be compounded to appear identical and placed in identical containers fitted with an electronic cap for monitoring medication adherence. Participants will be scheduled to return for a follow-up visit at two weeks, six weeks, and ten weeks after randomization. Blood and urine samples will be collected at each visit. Data will be collected by the principal investigator or trained study coordinator and will be electronically entered into a database stored on the secure Johns Hopkins servers through an online interface that is password protected. Urine will be collected and analyzed for 11-dehydro-thromboxane B2 at each study visit and constitutes the primary outcome of the study. Secondary outcomes will include measurement of platelet reactivity to U46619, a thromboxane A2 agonist, through identification of platelet surface markers CD62P, CD63, CD154 and PAC1.
The following adherence measurements will also be collected:
Drug discontinuation rate
Date and time of each dose of study medication obtained through electronic monitoring to assess adherence
The following clinical data will be collected at randomization:
1. Spirometry performed before and after administration of albuterol per American Thoracic Society protocol in a certified laboratory
The following clinical data will be collected at randomization and each subsequent study visit:
Respiratory symptom and quality of life questionnaires
Occurrence of COPD flares (exacerbations)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Sequential Assignment
Model Description
6-sequence, 3-period, 3-treatment sequential crossover trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sequence 1
Arm Type
Experimental
Arm Description
Week 1-2: aspirin 81mg
Week 5-6: aspirin 162mg
Week 9-10: aspirin 325mg
Arm Title
Sequence 2
Arm Type
Experimental
Arm Description
Week 1-2: aspirin 162mg
Week 5-6: aspirin 81mg
Week 9-10: aspirin 325mg
Arm Title
Sequence 3
Arm Type
Experimental
Arm Description
Week 1-2: aspirin 325mg
Week 5-6: aspirin 81mg
Week 9-10: aspirin 162mg
Arm Title
Sequence 4
Arm Type
Experimental
Arm Description
Week 1-2: aspirin 325mg
Week 5-6: aspirin 162mg
Week 9-10: aspirin 81mg
Arm Title
Sequence 5
Arm Type
Experimental
Arm Description
Week 1-2: aspirin 162mg
Week 5-6: aspirin 325mg
Week 9-10: aspirin 81mg
Arm Title
Sequence 6
Arm Type
Experimental
Arm Description
Week 1-2: aspirin 81mg
Week 5-6: aspirin 325mg
Week 9-10: aspirin 162mg
Intervention Type
Drug
Intervention Name(s)
Aspirin 81mg
Other Intervention Name(s)
Acetylsalicylic acid
Intervention Description
Aspirin 81mg once daily
Intervention Type
Drug
Intervention Name(s)
Aspirin 162 mg
Other Intervention Name(s)
Acetylsalicylic acid
Intervention Description
Aspirin 162 mg once daily
Intervention Type
Drug
Intervention Name(s)
Aspirin 325mg
Other Intervention Name(s)
Acetylsalicylic acid
Intervention Description
Aspirin 325mg once daily
Primary Outcome Measure Information:
Title
Change in urinary 11-dehydro-thromboxane B2 level
Description
Urine 11-dehydro-thromboxane B2 level (pg/mg Creatinine) - a urinary metabolite of thromboxane A2.
Time Frame
Baseline, week 2, week 6, week 10
Title
Change in serum thromboxane B2 level
Description
Serum thromboxane B2
Time Frame
Baseline, week 2, week 6, week 10
Secondary Outcome Measure Information:
Title
Change in proportion of platelets displaying CD62P
Description
Proportion of platelets displaying CD62P (activated platelets) following stimulation with U46619, a thromboxane A2 agonist.
Time Frame
Baseline, 2 weeks, 6 weeks, 10 weeks
Title
Change in proportion of platelets displaying CD63
Description
Proportion of platelets displaying CD63 (activated platelets) following stimulation with U46619, a thromboxane A2 agonist.
Time Frame
Baseline, 2 weeks, 6 weeks, 10 weeks
Title
Change in proportion of platelets displaying CD154
Description
Proportion of platelets displaying CD154 (activated platelets) following stimulation with U46619, a thromboxane A2 agonist
Time Frame
Baseline, 2 weeks, 6 weeks, 10 weeks
Title
Change in proportion of platelets displaying PAC1
Description
Proportion of platelets displaying PAC1 (activated platelets) following stimulation with U46619, a thromboxane A2 agonist
Time Frame
Baseline, 2 weeks, 6 weeks, 10 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
History of myocardial infarction, percutaneous coronary intervention, or stroke
Presence of coronary artery calcification on computed tomography (CT) scan by visual assessment
Currently taking antiplatelet therapy 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
Currently taking immunosuppressant medication
Active malignancy (other than non-melanoma skin cancer)
Uncontrolled hypertension
Pregnant or planning pregnancy in the next year
Plans to move residence away from the immediate area within the next 3 months
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wendy Lorizio, MD, MPH
Phone
410-510-2449
Email
wlorizi1@jhmi.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ashraf Fawzy, MD, MPH
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Bayview Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wendy Lorizio, MD, MPH
Phone
410-510-2449
Email
wlorizi1@jhmi.edu
12. IPD Sharing Statement
Plan to Share IPD
No
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Trial to Determine Effective Aspirin Dose in COPD
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