Clinical trial NCT02937077: Atrial Fibrillation in Cryptogenic Stroke and TIA
Official title: The Nordic Atrial Fibrillation and Stroke Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atrial Fibrillation
Ischemic Stroke
TIA
Keywords: etiology
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Ostfold Hospital Trust
name: Haukeland University Hospital
name: Rigshospitalet, Denmark
name: Bispebjerg Hospital
name: The Hospital of Vestfold
name: Sykehuset Telemark
name: Herlev Hospital
name: Nordlandssykehuset HF
name: Vestre Viken Hospital Trust
name: Helse Stavanger HF
name: Molde Hospital
name: Drammen sykehus
name: Diakonhjemmet Hospital
name: University Hospital of North Norway
name: Ullevaal University Hospital
name: Sykehuset Innlandet HF
name: Skane University Hospital
First posted: 2016-10-18
Enrollment: 259
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients admitted to stroke units with cryptogenic ischemic stroke or TIA

Brief summary: Background:

Different studies with real-life data and randomized controlled trials have shown a detection rate of paroxysmal atrial fibrillation (AF) of 10-20% in patients with cryptogenic stroke using insertable continuous cardiac monitoring for 6 months. More studies are needed, however, to identify factors which can be used to select the patients where the possibility of detecting AF with prolonged rhythm monitoring is highest, to evaluate the best duration of rhythm monitoring, to determine the optimal deﬁnition of short-term AF that warrants intervention and to evaluate whether intervention results in improved clinical outcomes.

Methods: The NOR-FIB study is a multi-centre prospective observational trial, designed to evaluate detection of AF in cryptogenic stroke and transient ischemic attack (TIA). Patients admitted with cryptogenic stroke or TIA in stroke units in the Nordic countries, aged 18-80 years are included and have the Reveal LINQ® Insertable cardiac monitor system implanted for 12 months for the purpose of AF detection. Biomarkers that may identify patients, who could derive the most clinical benefit from the detection of AF by prolonged monitoring, are being studied.

Conclusion: This NOR-FIB study will increase our knowledge regarding the occurrence of AF in patients with cryptogenic stroke and TIA that potentially can improve secondary prevention. The study will provide information on biomarkers that may be used to select cryptogenic TIA and stroke patients for long-term monitoring as well as information on the significance of short-term AF and optimal duration of cardiac rhythm monitoring.


Eligibility criteria: Inclusion Criteria:

1. Cryptogenic ischemic stroke patients or symptomatic TIA \< 21 days from symptom start.
2. A stroke/TIA is considered to be cryptogenic if no cause can be determined despite an extensive workup according to the standard protocol of the participating center. Before inclusion to the study, the following tests are required as standard tests to establish the diagnosis of cryptogenic stroke or TIA:

   1. Brain MRI or CT†
   2. 12-lead ECG for AF detection
   3. 24-h ECG monitoring for AF detection and premature atrial complex analysis (e.g. Holter)
   4. TEE (transesophageal echocardiography) highly recommended or TTE (transthoracic echocardiography)
   5. Colour Duplex ultrasound examination of the pre-cerebral arteries
   6. CTA or MRA of head and neck to rule out other causes of stroke pathologies
3. Age 18 to 80 at onset of TIA/stroke
4. A participation consent form signed by the patient or a legally authorized representative.

   * TIA cases with acute non-lacunar infarct on Diffusion Weighted Imaging are included as TIA events.

Exclusion Criteria:

1. Known etiology of TIA or stroke.
2. TIA without documented cerebral ischemia on Diffusion Weighed Imaging.
3. Untreated hyperthyroidism
4. Myocardial infarction less than 1 month prior to the stroke or TIA.
5. Coronary bypass grafting less than 1 month prior to the stroke or TIA.
6. Valvular heart disease requiring immediate surgical intervention.
7. History of atrial fibrillation or atrial flutter.
8. Patent Foramen Ovale (PFO) or PFO where there is or was an indication to start oral anticoagulation
9. Permanent indication for OAC treatment at enrollment.
10. Permanent contra-indication for OAC.
11. Life expectancy less than 1 year.
12. Pregnancy
13. An indication for an Implantable Pulse Generator (IPG), Implantable Cardioverter-Defibrillator (ICD), Cardiac Resynchronization Therapy (CRT) or an implantable hemodynamic monitoring system.
14. Patient otherwise not eligible for the study or adherent for follow-up (e.g. non-resident) or has concurrent disease which may affect clinical outcome (e.g. multiple sclerosis, cancer).

Primary outcomes:
measure: Atrial fibrillation detection rate
timeFrame: within 6 months
Secondary outcomes:
measure: AF detection rate
timeFrame: within 12 months
measure: Levels of miRNAs related to atrial fibrillation
timeFrame: 12 months
measure: Levels of NT-proBNP
timeFrame: baseline and 12 months
measure: Levels of Troponin-T
timeFrame: baseline and 12 months
measure: Levels of inflammation biomarkers
timeFrame: baseline and 12 months
measure: Prestroke/pre-TIA CHA2DS2-VASc score
timeFrame: baseline
measure: Incidence of recurrent stroke or TIA - percentage of stroke/TIA within 12 9. Incidence of recurrent stroke or TIA - percentage of stroke/TIA
timeFrame: 12 months
measure: Use of oral anticoagulation - percentage of patients who are using OAC drugs
timeFrame: 12 months
measure: Use of antiarrhythmic drugs - percentage of patients who are using antiarrhythmic drugs
timeFrame: 12 month
measure: Health Outcome as Evaluated by an EQ-5D Questionnaire - EQ-5D quality of life score
timeFrame: 12 months
Other outcomes:
Locations:
city: Sarpsborg
country: Norway
facility: Østfold Hospital Trust
state: Grålum
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Oslo University Hospital
name: Anne Hege Aamodt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oslo University Hospital
name: Dan Atar, MD, PhD
role: STUDY_CHAIR
References:
citation: Li L, Yiin GS, Geraghty OC, Schulz UG, Kuker W, Mehta Z, Rothwell PM; Oxford Vascular Study. Incidence, outcome, risk factors, and long-term prognosis of cryptogenic transient ischaemic attack and ischaemic stroke: a population-based study. Lancet Neurol. 2015 Sep;14(9):903-913. doi: 10.1016/S1474-4422(15)00132-5. Epub 2015 Jul 27.
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citation: Sanna T, Diener HC, Passman RS, Di Lazzaro V, Bernstein RA, Morillo CA, Rymer MM, Thijs V, Rogers T, Beckers F, Lindborg K, Brachmann J; CRYSTAL AF Investigators. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014 Jun 26;370(26):2478-86. doi: 10.1056/NEJMoa1313600.
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citation: Wu N, Chen X, Cai T, Wu L, Xiang Y, Zhang M, Li Y, Song Z, Zhong L. Association of inflammatory and hemostatic markers with stroke and thromboembolic events in atrial fibrillation: a systematic review and meta-analysis. Can J Cardiol. 2015 Mar;31(3):278-86. doi: 10.1016/j.cjca.2014.12.002. Epub 2014 Dec 9.
citation: Howlett PJ, Hatch FS, Alexeenko V, Jabr RI, Leatham EW, Fry CH. Diagnosing Paroxysmal Atrial Fibrillation: Are Biomarkers the Solution to This Elusive Arrhythmia? Biomed Res Int. 2015;2015:910267. doi: 10.1155/2015/910267. Epub 2015 Jul 1.