Atrial Fibrillation in Cryptogenic Stroke and TIA

Atrial Fibrillation Clinical Trial

— NOR-FIB  

Official title:

The Nordic Atrial Fibrillation and Stroke Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02937077
• Other study ID #: 2013/2371
• Status: Completed
• Start date: December 2016
• Est. completion date: October 2021

Study information

• Verified date: January 2022
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 259
• Est. completion date: October 2021
• Est. primary completion date: October 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• Atrial Fibrillation
• Ischemic Stroke
• Stroke
• TIA

Intervention

Device:
• Medtronic Reveal LINQ

Locations

Country	Name	City	State
Norway	Oslo University Hospital	Oslo
Norway	Østfold Hospital Trust	Sarpsborg	Grålum

Sponsors (18)

Lead Sponsor

Collaborator

Oslo University Hospital

Bispebjerg Hospital, Diakonhjemmet Hospital, Drammen sykehus, Haukeland University Hospital, Helse Stavanger HF, Herlev Hospital, Molde Hospital, Nordlandssykehuset HF, Ostfold Hospital Trust, Rigshospitalet, Denmark, Skane University Hospital, Sykehuset Innlandet HF, Sykehuset Telemark, The Hospital of Vestfold, Ullevaal University Hospital, University Hospital of North Norway, Vestre Viken Hospital Trust

Country where clinical trial is conducted

Norway, 

References & Publications (7)

Christensen LM, Krieger DW, Højberg S, Pedersen OD, Karlsen FM, Jacobsen MD, Worck R, Nielsen H, Aegidius K, Jeppesen LL, Rosenbaum S, Marstrand J, Christensen H. Paroxysmal atrial fibrillation occurs often in cryptogenic ischaemic stroke. Final results from the SURPRISE study. Eur J Neurol. 2014 Jun;21(6):884-9. doi: 10.1111/ene.12400. Epub 2014 Mar 15. — View 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. Review. — View 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. — View 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. — View Citation

Tomson TT, Passman R. The Reveal LINQ insertable cardiac monitor. Expert Rev Med Devices. 2015 Jan;12(1):7-18. doi: 10.1586/17434440.2014.953059. Epub 2014 Aug 26. Review. — View 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. Review. — View Citation

Ziegler PD, Rogers JD, Ferreira SW, Nichols AJ, Sarkar S, Koehler JL, Warman EN, Richards M. Real-World Experience with Insertable Cardiac Monitors to Find Atrial Fibrillation in Cryptogenic Stroke. Cerebrovasc Dis. 2015;40(3-4):175-81. doi: 10.1159/000439063. Epub 2015 Aug 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Atrial fibrillation detection rate		within 6 months
Secondary	AF detection rate		within 12 months
Secondary	Levels of miRNAs related to atrial fibrillation		12 months
Secondary	Levels of NT-proBNP		baseline and 12 months
Secondary	Levels of Troponin-T		baseline and 12 months
Secondary	Levels of inflammation biomarkers		baseline and 12 months
Secondary	Prestroke/pre-TIA CHA2DS2-VASc score		baseline
Secondary	Incidence of recurrent stroke or TIA - percentage of stroke/TIA within 12 9. Incidence of recurrent stroke or TIA - percentage of stroke/TIA		12 months
Secondary	Use of oral anticoagulation - percentage of patients who are using OAC drugs		12 months
Secondary	Use of antiarrhythmic drugs - percentage of patients who are using antiarrhythmic drugs		12 month
Secondary	Health Outcome as Evaluated by an EQ-5D Questionnaire - EQ-5D quality of life score		12 months