Atrial Fibrillation Detected by Continuous ECG Monitoring

Stroke Clinical Trial

— LOOP  

Official title:

Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-risk Individuals.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02036450
• Other study ID #: H-4-2013-025
• Secondary ID: 13-135225
• Status: Completed
• Phase: N/A
• Start date: January 2014
• Est. completion date: March 2021

Study information

• Verified date: March 2021
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The LOOP study aims to determine whether screening for atrial fibrillation (AF) with implantable loop recorder and initiation of oral anticoagulation (OAC) if AF is detected will reduce the risk of stroke and systemic arterial embolism in patients with risk factors for stroke.

Description:

Background: Ischemic stroke is an increasing health problem world-wide (Heidenreich PA, et al. Circulation 2011; PMID 21262990). At least 20% of ischemic strokes are attributable to atrial fibrillation (AF) (Marini C, et al. Stroke J Cereb Circ 2005; PMID 15879330). Another 30% are so-called cryptogenic, possibly related to undiagnosed AF (Brachmann J, et al. Circ Arrhythm Electrophysiol 2015; PMID 26763225). In approximately 30% of a general population of pacemaker or cardioverter defibrillator patients, previously unknown AF will be detected during the first 2-3 years after implantation (Healey JS, et al. N Engl J Med 2012; PMID 22236222; ASSERT). Although the majority of these AF episodes are short-lasting and asymptomatic, the ASSERT study found that such AF is associated with risk of stroke. Since this was published, screening for AF has received intensified attention by researchers and the industry, although available evidence does not yet support systematic mass screening. - Aims: The LOOP study will determine whether long-term continuous screening and initiation of OAC for AF episodes lasting ≥6 minutes will reduce the risk of stroke in patients with stroke risk factors. - Methods: Patients from the general population will receive a letter of invitation from one of four study centers located in 3 of Denmark's 5 administrative regions. Eligible study participants must be ≥70 years old and have ≥1 of the following stroke risk factors; hypertension, diabetes, heart failure or previous stroke, while any history of AF or existing cardiac implantable electronic device are exclusion criteria. A total of 6000 participants will be randomized 3:1 to control (n=4500) or to receive an implantable loop recorder with continuous remote monitoring (n=1500) and initiation of OAC if AF is detected. The primary endpoint is time to first stroke or systemic arterial embolism. The trial is event-driven and planned to continue until 279 adjudicated primary events have occurred. Sub-studies include AF characterization, health economic analyses, quality-of-life assessments, cognitive function assessments, and studies of risk markers from 12-lead ECG, genetics, cardiac and brain imaging, biochemistry, and more.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6000
• Est. completion date: March 2021
• Est. primary completion date: February 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years to 90 Years

Eligibility

Inclusion Criteria:

• Age 70-90 years, and
• Previously diagnosed with =1 of:
• Diabetes mellitus (type 1 or type 2, with or without medical therapy)
• Hypertension (with or without medical therapy)
• Heart failure
• Previous diagnosed stroke (previous transient ischemic attack is not considered an inclusion criterion)

Exclusion Criteria:

• History of atrial fibrillation or flutter irrespective of type
• Cardiac pacemaker or defibrillator (with or without re-synchronization therapy)
• Contraindication to oral anticoagulation therapy
• Anticoagulation therapy; vitamin K antagonists, direct oral anticoagulants, or (low-molecular) heparins. Therapy with platelet inhibitors such as acetyl-salicylic acid, clopidogrel, persantine is not considered an exclusion criterion
• Renal failure treated with permanent dialysis
• Uncorrected congenital heart disease, or severe valvular stenosis, obstructive cardiomyopathy, active myocarditis, or constrictive pericarditis.
• On a waiting list for major surgery (cardiac, thoracic or abdominal)
• Cardiac or thoracic surgery has been performed within 3 months from inclusion
• Any major organ transplant (e.g. lung, liver, heart, or kidney)
• Cytotoxic or cytostatic chemotherapy and/or radiation therapy for treatment of a malignancy within 6 months before randomization or clinical evidence of current malignancy with the following exceptions: Basal or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia, prostate cancer (if stable, localized disease with a life expectancy of > 2.5 years in the opinion of the investigator)
• Life-expectancy shorter than 6 months
• Known to be human immunodeficiency virus (HIV) positive with an expected survival of less than 5 years due to HIV infection
• Recent (within 3 months) history of alcohol or drug abuse based on self-reporting
• Any condition (e.g. psychiatric illness, dementia) or situation, that in the investigators opinion could put the subject at significant risk, confound the study results, or interfere significantly with the subject participation in the study
• Unwillingness to participate or patient does not understand Danish language

Related Conditions & MeSH terms

• Atrial Fibrillation
• Diabetes
• Hypertension
• Stroke

Intervention

Device:
• Implantable loop recorder (Medtronic Reveal LINQ(TM))
The patients in the experimental arm receive an implantable loop recorder (Medtronic Reveal LINQ(TM)) with continuous monitoring, and are followed by daily automated remote transmissions. New arrhythmia episodes are reviewed daily by an experienced medical doctor. If AF lasting =6 minutes is detected and confirmed by at least two senior cardiologists, OAC is initiated. Decision about specific type of OAC, and possible further clinical work-up or treatment, is left to the treating physician and the patient. The remote monitoring continues until end of service of the device, patient withdrawal or other end-of-study.

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen

Sponsors (6)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Aalborg University, Bispebjerg Hospital, Odense University Hospital, University of Southern Denmark, Zealand University Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (4)

Brachmann J, Morillo CA, Sanna T, Di Lazzaro V, Diener HC, Bernstein RA, Rymer M, Ziegler PD, Liu S, Passman RS. Uncovering Atrial Fibrillation Beyond Short-Term Monitoring in Cryptogenic Stroke Patients: Three-Year Results From the Cryptogenic Stroke and Underlying Atrial Fibrillation Trial. Circ Arrhythm Electrophysiol. 2016 Jan;9(1):e003333. doi: 10.1161/CIRCEP.115.003333. — View Citation

Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capucci A, Lau CP, Fain E, Yang S, Bailleul C, Morillo CA, Carlson M, Themeles E, Kaufman ES, Hohnloser SH; ASSERT Investigators. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012 Jan 12;366(2):120-9. doi: 10.1056/NEJMoa1105575. Erratum in: N Engl J Med. 2016 Mar 10;374(10):998. — View Citation

Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, Finkelstein EA, Hong Y, Johnston SC, Khera A, Lloyd-Jones DM, Nelson SA, Nichol G, Orenstein D, Wilson PW, Woo YJ; American Heart Association Advocacy Coordinating Committee; Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Clinical Cardiology; Council on Epidemiology and Prevention; Council on Arteriosclerosis; Thrombosis and Vascular Biology; Council on Cardiopulmonary; Critical Care; Perioperative and Resuscitation; Council on Cardiovascular Nursing; Council on the Kidney in Cardiovascular Disease; Council on Cardiovascular Surgery and Anesthesia, and Interdisciplinary Council on Quality of Care and Outcomes Research. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation. 2011 Mar 1;123(8):933-44. doi: 10.1161/CIR.0b013e31820a55f5. Epub 2011 Jan 24. — View Citation

Marini C, De Santis F, Sacco S, Russo T, Olivieri L, Totaro R, Carolei A. Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population-based study. Stroke. 2005 Jun;36(6):1115-9. Epub 2005 May 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to diagnosis of AF		At the completion of the event-driven trial, expected 4 years
Other	Time to initiation of OAC		At the completion of the event-driven trial, expected 4 years
Other	Time to adjudicated intracranial hemorrhage not classified as stroke		At the completion of the event-driven trial, expected 4 years
Other	Time to adjudicated hemorrhagic stroke		At the completion of the event-driven trial, expected 4 years
Other	Time to major bleeding as defined by the International Society on Thrombosis and Haemostasis criteria		At the completion of the event-driven trial, expected 4 years
Other	Presence of complications related to loop recorder implantation; infection, hematoma, or other complication related to device implantation requiring intervention		During implantable loop recorder monitoring, expected 3 years
Other	Change from baseline in quality of life	Quality of life assessed with the "EuroQol, 5 Dimensions with 5 Levels" instrument (EQ-5D-5L) with range 5-25 and higher values indicating higher quality of life.	3 years (from baseline to the at the fourth study visit)
Primary	Time to adjudicated stroke or systemic arterial embolism	Time to the first of one of the components of the combined primary endpoint; adjudicated stroke, or; adjudicated systemic arterial embolism	At the completion of the event-driven trial, expected 4 years
Secondary	Time to adjudicated ischemic stroke/transient ischemic attack/systemic arterial embolism	Time to the first of one of the components of the combined endpoint; adjudicated ischemic stroke, or; adjudicated transient ischemic attack, or; adjudicated systemic arterial embolism	At the completion of the event-driven trial, expected 4 years
Secondary	Time to adjudicated stroke, or systemic arterial embolism, or cardiovascular death	Time to the first of one of the components of the combined endpoint; adjudicated stroke, or; adjudicated systemic arterial embolism, or; adjudicated cardiovascular death	At the completion of the event-driven trial, expected 4 years
Secondary	Time to adjudicated cardiovascular death		At the completion of the event-driven trial, expected 4 years
Secondary	Time to death by any cause		At the completion of the event-driven trial, expected 4 years

External Links

•   Homepage for the LOOP study