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

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02697916
• Collaborator: Patient-Centered Outcomes Research Institute (Other), Mytrus (Other), Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN) (Other), Greater Plains Collaborative Clinical Data Research Network (Other), Mid-South Clinical Data Research Network (Other), Research Action for Health Network (REACHnet) (Other), Patient-Centered Scalable National Network for Effectiveness Research (Other), PaTH Clinical Data Research Network (Other), New York City Clinical Data Research Network (Other), Health eHeart Patient Powered Network (Other), OneFlorida Clinical Data Research Network (Other), HealthCore-Anthem Research Network (Other), Humana-HUMnet (Other), The Patient-Centered Network of Learning Health Systems (Other)
• Enrollment: 15,076
• Locations: 40
• Arms: 2
• Actual Duration (Months): 51
• Patients Per Site: 376.9
• Patients Per Site Per Month: 7.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerotic Cardiovascular Disease	Drug: aspirin	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15076 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness
• Actual Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Jun 30, 2020
• Actual Study Completion Date: Jun 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ASA 81mg aspirin 81mg	Drug: aspirin; 81mg of aspirin daily vs. 325mg of aspirin daily; Other Names: ASA
Active Comparator: ASA 325mg aspirin 325mg	Drug: aspirin; 81mg of aspirin daily vs. 325mg of aspirin daily; Other Names: ASA

Outcome Measures

Primary Outcome Measures

1. 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

1. Number of Participants Experiencing All-cause Death [Time of randomization through study completion, approximately 4 years]

2. Number of Participants Experiencing Hospitalization for Nonfatal MI [Time of randomization through study completion, approximately 4 years]

3. Number of Participants Experiencing Hospitalization for Nonfatal Stroke [Time of randomization through study completion, approximately 4 years]

4. 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]

5. 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.

Other Outcome Measures

1. Number of Participants Experiencing Hospitalization for Major Bleeding Complications With an Associated Blood Product Transfusion [Time of randomization through study completion, approximately 4 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Medical Center	Los Angeles	California	United States	90095
2	HealthCore	Wilmington	Delaware	United States	19801
3	University of Florida Cardiology - Springhill	Gainesville	Florida	United States	32606
4	Florida Hospital	Orlando	Florida	United States	32806
5	Orlando Health	Orlando	Florida	United States	32806
6	Bond Community Health Center	Tallahassee	Florida	United States	32301
7	Northwestern University	Chicago	Illinois	United States	60611
8	Rush University Medical Center	Chicago	Illinois	United States	60612
9	University of Chicago Medical Center	Chicago	Illinois	United States	60637
10	Indiana University	Indianapolis	Indiana	United States	46202
11	University of Iowa Hospitals & Clinics	Iowa City	Iowa	United States	52242
12	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
13	Ochsner Health System	New Orleans	Louisiana	United States	70112
14	Tulane University Heart & Vascular Institute	New Orleans	Louisiana	United States	70112
15	Johns Hopkins Medical Center	Baltimore	Maryland	United States	21287
16	University of Michigan	Ann Arbor	Michigan	United States	48109
17	Essentia Health St. Mary's Medical Center	Duluth	Minnesota	United States	55805
18	Allina Health	Minneapolis	Minnesota	United States	55407
19	Mayo Clinic	Rochester	Minnesota	United States	55905
20	University of Missouri	Columbia	Missouri	United States	65211
21	University of Nebraska Medical Center	Omaha	Nebraska	United States	68196
22	New York University School of Medicine	New York	New York	United States	10016
23	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
24	Weill Cornell Medicine of Cornell University	New York	New York	United States	10065
25	Montefiore Medical Center	New York	New York	United States	10461
26	UNC Chapel Hill	Chapel Hill	North Carolina	United States	27514
27	Duke University	Durham	North Carolina	United States	27701
28	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
29	Ohio State Univerity	Columbus	Ohio	United States	43210
30	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033
31	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
32	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
33	Vanderbilt University	Nashville	Tennessee	United States	37203
34	Baylor Scott and White Heart and Vascular Hospital	Dallas	Texas	United States	75226
35	University of Texas-Southwestern	Dallas	Texas	United States	75390
36	University of Texas Health Sciences Center at San Antonio	San Antonio	Texas	United States	78229
37	Intermountain Medical Center	Salt Lake City	Utah	United States	84107
38	University of Utah Hospitals and Clinics	Salt Lake City	Utah	United States	84112
39	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
40	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Duke University
• Patient-Centered Outcomes Research Institute
• Mytrus
• Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN)
• Greater Plains Collaborative Clinical Data Research Network
• Mid-South Clinical Data Research Network
• Research Action for Health Network (REACHnet)
• Patient-Centered Scalable National Network for Effectiveness Research
• PaTH Clinical Data Research Network
• New York City Clinical Data Research Network
• Health eHeart Patient Powered Network
• OneFlorida Clinical Data Research Network
• HealthCore-Anthem Research Network
• Humana-HUMnet
• The Patient-Centered Network of Learning Health Systems

Investigators

• Principal Investigator: William S. Jones, MD, Duke Clinical Research Institute
• Principal Investigator: Adrian F. Hernandez, MD MHS FAHA, Duke Clinical Research Institute

Study Documents (Full-Text)

• Study Protocol - Feb 12, 2020
• Statistical Analysis Plan - Feb 9, 2021

More Information

Additional Information:

• ADAPTABLE public website

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02697916
• Other Study ID Numbers: Pro00068525
• First Posted: Mar 3, 2016
• Last Update Posted: Jul 1, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Keywords provided by Duke University: aspirin; ACSD; PCORI
• Additional relevant MeSH terms: Cardiovascular Diseases; Atherosclerosis; Aspirin

Study Results

Participant Flow

Arm/Group Title	ASA 81mg	ASA 325mg
Arm/Group Description	aspirin 81mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily	aspirin 325mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily
Period Title: Overall Study
STARTED	7540	7536
COMPLETED	6962	6828
NOT COMPLETED	578	708

Baseline Characteristics

Arm/Group Title	ASA 81mg	ASA 325mg	Total
Arm/Group Description	aspirin 81mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily	aspirin 325mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily	Total of all reporting groups
Overall Participants	7540	7536	15076
Age (years) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [years]	66.9	66.8	66.8
Sex: Female, Male (Count of Participants)
Female	2307 30.6%	2417 32.1%	4724 31.3%
Male	5233 69.4%	5119 67.9%	10352 68.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	249 3.3%	232 3.1%	481 3.2%
Not Hispanic or Latino	6816 90.4%	6737 89.4%	13553 89.9%
Unknown or Not Reported	475 6.3%	567 7.5%	1042 6.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	69 0.9%	45 0.6%	114 0.8%
Asian	82 1.1%	64 0.8%	146 1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	664 8.8%	647 8.6%	1311 8.7%
White	6014 79.8%	5976 79.3%	11990 79.5%
More than one race	71 0.9%	63 0.8%	134 0.9%
Unknown or Not Reported	640 8.5%	741 9.8%	1381 9.2%

Outcome Measures

1. Primary Outcome

Title	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 Frame	Time of randomization through study completion, approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ASA 81mg	ASA 325mg
Arm/Group Description	aspirin 81mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily	aspirin 325mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily
Measure Participants	7434	7330
Count of Participants [Participants]	590 7.8%	569 7.6%

2. Secondary Outcome

Title	Number of Participants Experiencing All-cause Death
Time Frame	Time of randomization through study completion, approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ASA 81mg	ASA 325mg
Arm/Group Description	aspirin 81mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily	aspirin 325mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily
Measure Participants	7434	7330
Count of Participants [Participants]	315 4.2%	357 4.7%

3. Secondary Outcome

Title	Number of Participants Experiencing Hospitalization for Nonfatal MI
Time Frame	Time of randomization through study completion, approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ASA 81mg	ASA 325mg
Arm/Group Description	aspirin 81mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily	aspirin 325mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily
Measure Participants	7434	7330
Count of Participants [Participants]	228 3%	213 2.8%

4. Secondary Outcome

Title	Number of Participants Experiencing Hospitalization for Nonfatal Stroke
Time Frame	Time of randomization through study completion, approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ASA 81mg	ASA 325mg
Arm/Group Description	aspirin 81mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily	aspirin 325mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily
Measure Participants	7434	7330
Count of Participants [Participants]	102 1.4%	92 1.2%

5. Secondary Outcome

Title	Number of Participants Requiring Coronary Revascularization Procedures (Percutaneous Coronary Intervention [PCI] or Coronary Artery Bypass Grafting [CABG])
Time Frame	Time of randomization through study completion, approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ASA 81mg	ASA 325mg
Arm/Group Description	aspirin 81mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily	aspirin 325mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily
Measure Participants	7434	7330
Count of Participants [Participants]	471 6.2%	446 5.9%

6. Secondary Outcome

Title	Quality of Life and Functional Status, as Measured on a 5-point Scale
Description	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.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ASA 81mg	ASA 325mg
Arm/Group Description	aspirin 81mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily	aspirin 325mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily
Measure Participants	7540	7536
Describe Current Health	2.77 (.011)	2.8 (.011)
Able to Run Errands and Shop	1.65 (.011)	1.66 (.012)
In the past 7 Days, Felt Depressed	1.69 (.010)	1.7 (.011)
In the past 7 Days, Felt Fatigued	2.25 (.012)	2.27 (.012)
In the past 7 Days, Problems with Sleep	2.06 (.012)	2.10 (.012)
Trouble doing Regular Activities	1.84 (.012)	1.88 (.012)
In the past 7 Days, Pain interfered	2.06 (.013)	2.02 (.013)

7. Other Pre-specified Outcome

Title	Number of Participants Experiencing Hospitalization for Major Bleeding Complications With an Associated Blood Product Transfusion
Time Frame	Time of randomization through study completion, approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ASA 81mg	ASA 325mg
Arm/Group Description	aspirin 81mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily	aspirin 325mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily
Measure Participants	7434	7330
Count of Participants [Participants]	53 0.7%	44 0.6%

Adverse Events

Time Frame	Up to 50 months
Arm/Group Title	ASA 81mg		ASA 325mg
Arm/Group Description	aspirin 81mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily		aspirin 325mg aspirin: 81mg of aspirin daily vs. 325mg of aspirin daily
All Cause Mortality
	ASA 81mg		ASA 325mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	315/7434 (4.2%)		357/7330 (4.9%)
Serious Adverse Events
	ASA 81mg		ASA 325mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	383/7434 (5.2%)		349/7330 (4.8%)
Cardiac disorders
Non-Fatal MI	228/7434 (3.1%)	228	213/7330 (2.9%)	213
Major Bleeding	53/7434 (0.7%)	53	44/7330 (0.6%)	44
Vascular disorders
Non-Fatal Stroke	102/7434 (1.4%)	102	92/7330 (1.3%)	92
Other (Not Including Serious) Adverse Events
	ASA 81mg		ASA 325mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	491/7434 (6.6%)		471/7330 (6.4%)
Cardiac disorders
PCI or CABG	471/7434 (6.3%)	471	446/7330 (6.1%)	446
Transient ischemia attack (TIA)	20/7434 (0.3%)	20	25/7330 (0.3%)	25

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.