CRYptogenic STroke And underlying AF (CRYSTAL AF )

Stroke is a devastating disease. It has been shown that it is the third leading
cause of mortality in the US and the leading cause of long term disability.
Stroke of undetermined cause accounts for approximately 25-30% of ischemic
strokes and it is assumed that asymptomatic paroxysmal atrial fibrillation (AF)
may be an important underlying cause.
The American and European guidelines recommend patients with cryptogenic stroke
to take antiplatelets for secondary prevention (stroke recurrence). However,
when a stroke patient is found to have AF the guidelines recommend
anticoagulation due to its superior efficacy over antiplatelets for stroke
prevention. As several studies have shown that oral anticoagulation reduced the
risk of stroke in AF patients by up to 80% and given the fact that that stroke
with AF is associated with greater disability and mortality than those without
AF, establishing the presence of underlying AF is of clear clinical importance.
The current available technologies to identify episodes of AF seem to be
inadequate.
With this study we aim to provide clinical evidence that long term monitoring
by Reveal XT in patients with Cryptogenic Stroke has AF diagnostic superiority
compared to usual care and we investigate the true incidence of AF in this
population.

PRIMARY OBJECTIVE
To evaluate the time to first documented event of atrial fibrillation by 6
months continuous rhythm monitoring versus Standard of Care treatment in
patients with a recent cryptogenic stroke or TIA without documented history of
atrial fibrillation

SECONDARY OBJECTIVES
The key secondary objective with pre-specified hypotheses to be tested:
1. To evaluate the time to first documented event of atrial fibrillation by 12
months* continuous rhythm monitoring versus Control treatment in subjects with
a recent cryptogenic stroke or TIA without documented history of atrial
fibrillation
2. To compare the incidence of recurrent stroke or TIA in subjects with a
recent cryptogenic stroke or TIA randomized to long-term rhythm monitoring
versus Control treatment.
3. To compare the change, and reasons for change, in use of oral
anticoagulation and of antiarrhythmic drugs over time in both arms
4. To compare health outcome in both arms
5. To describe the economic and clinical disease burden and the care pathways
of enrolled subjects
6. To investigate the role of the Patient Assistant in the time to AF diagnosis
in subjects implanted with the Reveal XT

The CRYSTAL AF study is a 1:1 randomized prospective multicenter study in which
approximately 450 patients will be included in about 45 sites in the United
States, Europe, and Canada.

Randomization will be done based on 2 stratifiers:
1. Stroke or TIA
2. Presence of PFO (yes/no)

The study will be conducted using the commercially released Reveal XT
Insertable Cardiac Monitor System (CE marked), which consists of the following
components:
* Reveal XT model 9529 Insertable Cardiac Monitor or successor model
* Medtronic Model 2090 CareLink programmer with software model SW 0007 or
successor programmer/software
* Reveal XT Patient Assistant model 9539, or successor model

Risks of the Reveal XT implantation is comparable of the implantation would not
take place because of participation in this study.