Trial Design
Cryptogenic Stroke and underlying Atrial Fibrillation (CRYSTAL AF): Design and rationale

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Background

Patients with atrial fibrillation (AF) are at increased risk for ischemic stroke. In patients who have suffered a stroke, screening for AF is routinely performed only for a short period after the stroke as part of the evaluation for possible causes. If AF is detected after an ischemic stroke, oral anticoagulation therapy is recommended for secondary stroke prevention. In 25% to 30% of stroke patients, the stroke mechanism cannot be determined (cryptogenic stroke). The incidence of paroxysmal AF undetected by short-term monitoring in patients with cryptogenic stroke is unknown, but has important therapeutic implications on patient care. The optimum monitoring duration and method of AF detection after stroke are unknown. The purpose of this study is to evaluate the incidence of AF and time to AF detection in patients with cryptogenic stroke using an insertable cardiac monitor.

Study Design

The CRYSTAL AF trial is a randomized prospective study to evaluate a novel approach to long-term monitoring for AF detection in patients with cryptogenic stroke. Four hundred fifty cryptogenic stroke patients (by definition, without a history of AF) will be enrolled at approximately 50 sites in Europe, Canada, and the United States. Patients will be randomized in a 1:1 fashion to standard arrhythmia monitoring (control arm) or implantation of the subcutaneous cardiac monitor (Reveal XT; Medtronic, Inc, Minneapolis, MN) (continuous monitoring arm).

Outcomes

The primary end point is time to detection of AF within 6 months after stroke. The clinical follow-up period will be at least 12 months. Study completion is expected at the end of 2012.

Section snippets

Background

Atrial fibrillation (AF) (permanent, persistent, and paroxysmal) is a potent risk factor for first and recurrent ischemic stroke. It is associated with a 5-fold increased risk for stroke and embolism and is responsible for at least one sixth of all ischemic strokes.1, 2 However, this may be an underestimate, as AF may be asymptomatic and paroxysmal and remain undetected with the short-term monitoring that most patients receive after an ischemic stroke.

In approximately 25% to 30% of cases of

Study design

The CRYSTAL AF trial (www.clinicaltrials.gov registration: NCT00924638) is a prospective, multicenter, randomized, unblinded study comparing the incidence of AF detection using REVEAL XT to routine monitoring in patients with cryptogenic stroke or TIA. The primary end point is time to AF detection in the 6 months after randomization. All end points will be adjudicated by an adjudication committee, blinded to the treatment arm, where possible. Approximately 50 centers in Europe, Canada, and the

Discussion

The CRYSTAL AF trial is a phase IV evaluation of the Reveal XT implantable cardiac monitor for the detection of AF in patients with a recent cryptogenic stroke.

The Reveal XT is currently the only implantable leadless device that has the ability to detect AF with a validated algorithm.15 A previous study has outlined the performance of the device under real-life conditions.14 Other implantable cardiac monitors might also have the capability of detecting AF; however, the safety and accuracy of

Disclosures

Authors Brachmann, Diener, Morillo, Sanna, Bernstein, Di Lazzaro, and Passman have all received grant support from the study sponsor of CRYSTAL AF, Medtronic, Inc (Minneapolis, MN). Dr Bernstein has served as a promotional speaker for Medtronic; Northwestern University receives payment for Dr Bernstein's work on the steering committee of CRYSTAL AF. Mr Beckers is an employee of Medtronic Bakken Research Center, the Netherlands. The authors are solely responsible for the design and conduct of

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Cited by (122)

  • Long-term detection of atrial fibrillation with insertable cardiac monitors in a real-world cryptogenic stroke population

    2017, International Journal of Cardiology
    Citation Excerpt :

    The CRYSTAL-AF study was a moderately sized trial which randomized patients with a recent cryptogenic stroke to standard of care monitoring or intensive monitoring with an ICM [12]. While the trial clearly demonstrated the superiority of monitoring with an ICM compared to standard of care monitoring [13], the study reflected the specific conditions and inclusion/exclusion criteria set forth by the trial design [12]. We previously reported the short-term (6-month) incidence of AF in a large, real-world cohort of patients with an ICM placed for AF detection following cryptogenic stroke [14].

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For a complete list of Steering Committee members see the online Appendix.

RCT# NCT00924638.

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