Clinical trial NCT04593030: Replication of the ARISTOTLE Anticoagulant Trial in Healthcare Claims Data
Official title: Replication of the ARISTOTLE Anticoagulant Trial in Healthcare Claims Data
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atrial Fibrillation
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2020-10-19
Enrollment: 220518
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study will involve a new user, parallel group, cohort study design comparing apixaban to warfarin. The patients will be required to have continuous enrollment during baseline period of 180 days before initiation of apixaban or the comparator drug (cohort entry date). Follow-up for the outcome, begins the day after drug initiation.

Brief summary: Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Detailed description: This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.

Eligibility criteria: Please see: https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions.

Eligible cohort entry dates: Market availability of apixaban in the U.S. started on December 28, 1012. For Marketscan: Jan 1, 2013 -Dec 31, 2018 (end of data availability). For Optum: Jan 1, 2013-Dec 31, 2019 (end of data availability). For Medicare: Jan 1, 2013 -Dec 31, 2017.

Inclusion Criteria:

* 1. Age ≥ 18 years
* 2. Atrial fibrillation - either of the following:

  * 2a. In atrial fibrillation or atrial flutter not due to a reversible cause and documented by ECG at the time of enrollment
  * 2b. If not in atrial fibrillation/flutter at the time of enrollment, must have atrial fibrillation/flutter documented on two separate occasions, not due to a reversible cause at least 2 weeks apart in the 12 months prior to enrollment. Atrial fibrillation/flutter may be documented by ECG, or as an episode lasting at least one minute on a rhythm strip, Holter recording, or intracardiac electrogram (from an implanted pacemaker or defibrillator)
* 3. One or more of the following risk factor(s) for stroke:

  * 3a. Age 75 years or older
  * 3b. Prior stroke, TIA, or systemic embolus
  * 3c. Either symptomatic congestive heart failure within 3 months or left ventricular dysfunction with an LV ejection fraction (LVEF) ≤ 40% by echocardiography, radionuclide study or contrast angiography
  * 3d. Diabetes mellitus
  * 3e. Hypertension requiring pharmacological treatment

Exclusion Criteria:

* 2. Clinically significant (moderate or severe) mitral stenosis
* 3. Increased bleeding risk that is believed to be a contraindication to oral anticoagulation (e.g. previous intracranial hemorrhage)
* 4. Conditions other than atrial fibrillation that require chronic anticoagulation (e.g. prosthetic mechanical heart valve)
* 5. Persistent, uncontrolled hypertension (systolic BP \> 180 mm Hg, or diastolic BP \> 100 mm Hg)
* 6. Active infective endocarditis
* 11. Simultaneous treatment with both aspirin and a thienopyridine (e.g., clopidogrel, ticlopidine)
* 12. Severe comorbid condition with life expectancy of ≤ 1 year
* 13. Active alcohol or drug abuse, or psychosocial reasons that make study participation impractical
* 14. Recent ischemic stroke (within 7 days)
* 15. Severe renal insufficiency (serum creatinine \> 2.5 mg/dL or a calculated creatinine clearance \< 25 mL/min, See Section 6.3.2.2)
* 17. Platelet count ≤ 100,000/ mm3
* 18. Hemoglobin \< 9 g/dL
* 19. Women of child bearing potential (WOCBP) unwilling or unable to use an acceptable method to avoid pregnancy

Primary outcomes:
measure: Relative hazard of composite outcome of Stroke and Systemic Embolism
timeFrame: [Time Frame: Through study completion (a median of 98 days)]
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham And Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Jessica Franklin, PhD
role: PRINCIPAL_INVESTIGATOR
References: