Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term

Not Applicable

Completed

Conditions: Atherosclerotic Cardiovascular Disease

Interventions: Drug: aspirin

Registration Number: NCT02697916

Lead Sponsor: Duke University

Brief Summary: ADAPTABLE is a pragmatic clinical trial in which 15,000 patients who are at high risk for ischemic events will be randomly assigned in a 1:1 ratio to receive an aspirin dose of 81 mg/day vs. 325 mg/day. Study participants will be enrolled over 38 months. Maximum follow-up will be 50 months. The purpose of the study is to identify the optimal dose of aspirin for secondary prevention in patients with Atherosclerotic cardiovascular disease (ASCVD). The primary endpoint is a composite of all-cause death, hospitalization for MI, or hospitalization for stroke. The primary safety endpoint is hospitalization for major bleeding with an associated blood product transfusion.

Detailed Description: In this pragmatic, patient-centered clinical trial, the investigators will compare the effectiveness of two doses of aspirin (81 mg and 325 mg) currently in widespread use in the United States in the secondary-prevention population of patients with established ASCVD. The trial will use a novel format that uses existing electronic health records (EHRs), as well as a web-based patient portal to collect patient-reported outcomes (PROs), and available patient encounter data to supplement/support the EHR. Patients who are identified as candidates for the trial will be directed to the electronic patient portal for the eConsent as well as an abbreviated eligibility confirmation and randomization. One of the important aims of ADAPTABLE is to engage patients, their healthcare providers, and trial investigators in using the infrastructure PCORnet has developed and continues to refine. A total of 15,000 high-risk patients with ASCVD will be randomly assigned (in an open-label fashion) in a 1:1 ratio to instructions to use a daily aspirin dose of either 81 mg or 325 mg daily. The investigators expect the entire sample of patients will be enrolled over 38 months, with a maximum follow-up of 50 months.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15076

Inclusion Criteria

Known atherosclerotic cardiovascular disease (ASCVD), defined by a history of prior myocardial infarction, prior coronary angiography showing ≥75% stenosis of at least one epicardial coronary vessel, or prior coronary revascularization procedures (either PCI or CABG), or history of chronic heart disease, CAD, ASCVD
Age ≥ 18 years
No known safety concerns or side effects considered to be related to aspirin, including
No history of significant allergy to aspirin such as anaphylaxis, urticaria, or significant gastrointestinal intolerances
No history of significant GI bleed within the past 12 months
Significant bleeding disorders that preclude the use of aspirin
Access to the Internet. In the event that the CDRNs are notified that a cohort of patients without internet access can be included, then patient agreement will be obtained during the consent process to provide follow-up information by telephone contact with the DCRI Call Center.
Not currently treated with an oral anticoagulant - either warfarin or a novel anticoagulant (dabigatran, rivaroxaban, apixaban, edoxaban) - and not planned to be treated in the future with an oral anticoagulant for existing indications such as atrial fibrillation, deep venous thrombosis, or pulmonary embolism.
Not currently treated with ticagrelor and not planned to be treated in the future with ticagrelor.
Female patients who are not pregnant or nursing an infant
Estimated risk of a major cardiovascular event (MACE) > 8% over next 3 years as defined by the presence of at least one or more of the following enrichment factors:
Age > 65 years
Serum creatinine > 1.5 mg/dL
Diabetes mellitus (Type 1 or Type 2)
3-vessel coronary artery disease
Cerebrovascular disease and/or peripheral arterial disease
Left ventricular ejection fraction (LVEF) < 50%
Current cigarette smoker
Chronic systolic or diastolic heart failure
SBP > 140 (within past 12 mos)
LDL > 130 (within past 12 mos)

Exclusion Criteria

There will be no exclusions for any upper age limit, comorbid conditions, or concomitant medications other than oral anticoagulants and ticagrelor that are used at the time of randomization, or are planned to be used during the study follow-up.
Patients and sites interested in participating must be part of the listed health systems collaborators.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ASA 325mg	aspirin	aspirin 325mg
ASA 81mg	aspirin	aspirin 81mg

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing All-cause Death, Hospitalization for Nonfatal MI, or Hospitalization for Nonfatal Stroke in High-risk Patients With a History of MI or Documented Atherosclerotic Cardiovascular Disease (ASCVD)	Time of randomization through study completion, approximately 4 years

Secondary Outcome Measures

Name	Time	Method
Number of Participants Experiencing Hospitalization for Nonfatal MI	Time of randomization through study completion, approximately 4 years
Number of Participants Requiring Coronary Revascularization Procedures (Percutaneous Coronary Intervention [PCI] or Coronary Artery Bypass Grafting [CABG])	Time of randomization through study completion, approximately 4 years
Number of Participants Experiencing All-cause Death	Time of randomization through study completion, approximately 4 years
Quality of Life and Functional Status, as Measured on a 5-point Scale	2 years	Quality of life measures are based on an ordinal scale from 1-5, where 1 corresponds to the best outcome and 5 to the worst. Model-based mean score estimates are obtained from mixed models of each quality of life measure.
Number of Participants Experiencing Hospitalization for Nonfatal Stroke	Time of randomization through study completion, approximately 4 years

Trial Locations

Locations (40): New York University School of Medicine
🇺🇸
New York, New York, United States
Weill Cornell Medicine of Cornell University
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New York, New York, United States
University of Iowa Hospitals & Clinics
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Iowa City, Iowa, United States
Florida Hospital
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Orlando, Florida, United States
University of Missouri
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Columbia, Missouri, United States
UNC Chapel Hill
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Chapel Hill, North Carolina, United States
Essentia Health St. Mary's Medical Center
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Duluth, Minnesota, United States
Tulane University Heart & Vascular Institute
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New Orleans, Louisiana, United States
Northwestern University
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Chicago, Illinois, United States
Rush University Medical Center
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Chicago, Illinois, United States
UCLA Medical Center
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Los Angeles, California, United States
Johns Hopkins Medical Center
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Baltimore, Maryland, United States
Ohio State Univerity
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Columbus, Ohio, United States
Temple University Hospital
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Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
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Pittsburgh, Pennsylvania, United States
Baylor Scott and White Heart and Vascular Hospital
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Dallas, Texas, United States
University of Texas-Southwestern
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Dallas, Texas, United States
Indiana University
🇺🇸
Indianapolis, Indiana, United States
Allina Health
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Minneapolis, Minnesota, United States
University of Chicago Medical Center
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Chicago, Illinois, United States
Icahn School of Medicine at Mount Sinai
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New York, New York, United States
Penn State Milton S Hershey Medical Center
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Hershey, Pennsylvania, United States
Orlando Health
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Orlando, Florida, United States
HealthCore
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Wilmington, Delaware, United States
University of Michigan
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Ann Arbor, Michigan, United States
Intermountain Medical Center
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Salt Lake City, Utah, United States
University of Nebraska Medical Center
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Omaha, Nebraska, United States
University of Florida Cardiology - Springhill
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Gainesville, Florida, United States
Duke University
🇺🇸
Durham, North Carolina, United States
Mayo Clinic
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Rochester, Minnesota, United States
Vanderbilt University
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Nashville, Tennessee, United States
Bond Community Health Center
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Tallahassee, Florida, United States
University of Utah Hospitals and Clinics
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Salt Lake City, Utah, United States
Ochsner Health System
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New Orleans, Louisiana, United States
Medical College of Wisconsin
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Milwaukee, Wisconsin, United States
Marshfield Clinic
🇺🇸
Marshfield, Wisconsin, United States
University of Texas Health Sciences Center at San Antonio
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San Antonio, Texas, United States
Wake Forest University Health Sciences
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Winston-Salem, North Carolina, United States
Montefiore Medical Center
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New York, New York, United States
University of Kansas Medical Center
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Kansas City, Kansas, United States