Clinical trial NCT02697916: Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term
Official title: Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atherosclerotic Cardiovascular Disease
Keywords: aspirin
ACSD
PCORI
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: Medidata Solutions
name: Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN)
name: Greater Plains Collaborative Clinical Data Research Network
name: Mid-South Clinical Data Research Network
name: Research Action for Health Network (REACHnet)
name: The Patient-Oriented Scalable National Network for Effectiveness Research
name: PaTH Clinical Data Research Network
name: New York City Clinical Data Research Network
name: The Health eHeart Alliance
name: OneFlorida Clinical Data Research Network
name: HealthCore-Anthem Research Network
name: Humana Inc.
name: The Patient-Centered Network of Learning Health Systems
First posted: 2016-03-03
Enrollment: 15076
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: Time of randomization through study completion, approximately 4 years
Secondary outcomes:
measure: Number of Participants Experiencing All-cause Death
timeFrame: Time of randomization through study completion, approximately 4 years
measure: Number of Participants Experiencing Hospitalization for Nonfatal MI
timeFrame: Time of randomization through study completion, approximately 4 years
measure: Number of Participants Experiencing Hospitalization for Nonfatal Stroke
timeFrame: Time of randomization through study completion, approximately 4 years
measure: Number of Participants Requiring Coronary Revascularization Procedures (Percutaneous Coronary Intervention [PCI] or Coronary Artery Bypass Grafting [CABG])
timeFrame: Time of randomization through study completion, approximately 4 years
measure: Quality of Life and Functional Status, as Measured on a 5-point Scale
timeFrame: 2 years
Other outcomes:
measure: Number of Participants Experiencing Hospitalization for Major Bleeding Complications With an Associated Blood Product Transfusion
timeFrame: Time of randomization through study completion, approximately 4 years
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Wilmington
country: United States
facility: HealthCore
state: Delaware
city: Gainesville
country: United States
facility: University of Florida Cardiology - Springhill
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Tallahassee
country: United States
facility: Bond Community Health Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Health System
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Heart & Vascular Institute
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Medical Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Duluth
country: United States
facility: Essentia Health St. Mary's Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: Allina Health
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine of Cornell University
state: New York
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: Ohio State Univerity
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: Baylor Scott and White Heart and Vascular Hospital
state: Texas
city: Dallas
country: United States
facility: University of Texas-Southwestern
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Sciences Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospitals and Clinics
state: Utah
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Duke Clinical Research Institute
name: William S. Jones, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke Clinical Research Institute
name: Adrian F. Hernandez, MD MHS FAHA
role: PRINCIPAL_INVESTIGATOR
References:
citation: O'Brien EC, Mulder H, Jones WS, Hammill BG, Sharlow A, Hernandez AF, Curtis LH. Concordance Between Patient-Reported Health Data and Electronic Health Data in the ADAPTABLE Trial. JAMA Cardiol. 2022 Dec 1;7(12):1235-1243. doi: 10.1001/jamacardio.2022.3844.
citation: Jones WS, Mulder H, Wruck LM, Pencina MJ, Kripalani S, Munoz D, Crenshaw DL, Effron MB, Re RN, Gupta K, Anderson RD, Pepine CJ, Handberg EM, Manning BR, Jain SK, Girotra S, Riley D, DeWalt DA, Whittle J, Goldberg YH, Roger VL, Hess R, Benziger CP, Farrehi P, Zhou L, Ford DE, Haynes K, VanWormer JJ, Knowlton KU, Kraschnewski JL, Polonsky TS, Fintel DJ, Ahmad FS, McClay JC, Campbell JR, Bell DS, Fonarow GC, Bradley SM, Paranjape A, Roe MT, Robertson HR, Curtis LH, Sharlow AG, Berdan LG, Hammill BG, Harris DF, Qualls LG, Marquis-Gravel G, Modrow MF, Marcus GM, Carton TW, Nauman E, Waitman LR, Kho AN, Shenkman EA, McTigue KM, Kaushal R, Masoudi FA, Antman EM, Davidson DR, Edgley K, Merritt JG, Brown LS, Zemon DN, McCormick TE 3rd, Alikhaani JD, Gregoire KC, Rothman RL, Harrington RA, Hernandez AF; ADAPTABLE Team. Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease. N Engl J Med. 2021 May 27;384(21):1981-1990. doi: 10.1056/NEJMoa2102137. Epub 2021 May 15.
citation: Ahmad FS, Ricket IM, Hammill BG, Eskenazi L, Robertson HR, Curtis LH, Dobi CD, Girotra S, Haynes K, Kizer JR, Kripalani S, Roe MT, Roumie CL, Waitman R, Jones WS, Weiner MG. Computable Phenotype Implementation for a National, Multicenter Pragmatic Clinical Trial: Lessons Learned From ADAPTABLE. Circ Cardiovasc Qual Outcomes. 2020 Jun;13(6):e006292. doi: 10.1161/CIRCOUTCOMES.119.006292. Epub 2020 May 29.
citation: Marquis-Gravel G, Roe MT, Robertson HR, Harrington RA, Pencina MJ, Berdan LG, Hammill BG, Faulkner M, Munoz D, Fonarow GC, Nallamothu BK, Fintel DJ, Ford DE, Zhou L, Daugherty SE, Nauman E, Kraschnewski J, Ahmad FS, Benziger CP, Haynes K, Merritt JG, Metkus T, Kripalani S, Gupta K, Shah RC, McClay JC, Re RN, Geary C, Lampert BC, Bradley SM, Jain SK, Seifein H, Whittle J, Roger VL, Effron MB, Alvarado G, Goldberg YH, VanWormer JL, Girotra S, Farrehi P, McTigue KM, Rothman R, Hernandez AF, Jones WS. Rationale and Design of the Aspirin Dosing-A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) Trial. JAMA Cardiol. 2020 May 1;5(5):598-607. doi: 10.1001/jamacardio.2020.0116.