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Atrial Fibrillation Detected by Continuous ECG Monitoring (LOOP)

Primary Purpose

Atrial Fibrillation, Stroke, Hypertension

Status

Completed

Phase

Not Applicable

Locations

Denmark

Study Type

Interventional

Intervention

Implantable loop recorder (Medtronic Reveal LINQ(TM))

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring atrial fibrillation, cardiac arrhythmia, stroke, implantable loop recorder, bleeding, anticoagulation, hypertension, diabetes, heart failure, mortality

Eligibility Criteria

70 Years - 90 Years (Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Rigshospitalet

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

ILR group

Control group

Arm Description

Receive implantable loop recorder (ILR, Medtronic Reveal LINQ(TM)) with continuous monitoring, and will be followed by daily automated remote transmissions. Study visits are scheduled annually until the 4th visit, and furthermore, endpoints are collected via lookup in medical records and registries on at least an annual basis until the finalization of the trial.

Followed according to standard care, i.e. by their general practitioner. Study visits are scheduled at inclusion and after 3 years. Furthermore, the participants are contacted by telephone after 1 and 2 years of follow-up, and endpoints are collected via lookup in medical records and registries on at least an annual basis until the finalization of the trial.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

Time to adjudicated cardiovascular death

Time to death by any cause

Full Information

NCT ID

NCT02036450

First Posted

January 8, 2014

Last Updated

March 8, 2021

Sponsor

Rigshospitalet, Denmark

Collaborators

Bispebjerg Hospital, Zealand University Hospital, Odense University Hospital, University of Southern Denmark, Aalborg University

1. Study Identification

Unique Protocol Identification Number

NCT02036450

Brief Title

Atrial Fibrillation Detected by Continuous ECG Monitoring

Acronym

LOOP

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Completed

Study Start Date

January 2014 (undefined)

Primary Completion Date

February 2020 (Actual)

Study Completion Date

March 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Rigshospitalet, Denmark

Collaborators

Bispebjerg Hospital, Zealand University Hospital, Odense University Hospital, University of Southern Denmark, Aalborg University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atrial Fibrillation, Stroke, Hypertension, Diabetes

Keywords

atrial fibrillation, cardiac arrhythmia, stroke, implantable loop recorder, bleeding, anticoagulation, hypertension, diabetes, heart failure, mortality

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

6000 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ILR group

Arm Type

Experimental

Arm Description

Arm Title

Control group

Arm Type

No Intervention

Arm Description

Intervention Type

Device

Intervention Name(s)

Implantable loop recorder (Medtronic Reveal LINQ(TM))

Intervention Description

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.

Primary Outcome Measure Information:

Title

Time to adjudicated stroke or systemic arterial embolism

Description

Time to the first of one of the components of the combined primary endpoint adjudicated stroke, or adjudicated systemic arterial embolism

Time Frame

At the completion of the event-driven trial, expected 4 years

Secondary Outcome Measure Information:

Title

Time to adjudicated ischemic stroke/transient ischemic attack/systemic arterial embolism

Description

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

Time Frame

At the completion of the event-driven trial, expected 4 years

Title

Time to adjudicated stroke, or systemic arterial embolism, or cardiovascular death

Description

Time to the first of one of the components of the combined endpoint adjudicated stroke, or adjudicated systemic arterial embolism, or adjudicated cardiovascular death

Time Frame

At the completion of the event-driven trial, expected 4 years

Title

Time to adjudicated cardiovascular death

Time Frame

At the completion of the event-driven trial, expected 4 years

Title

Time to death by any cause

Time Frame

At the completion of the event-driven trial, expected 4 years

Other Pre-specified Outcome Measures:

Title

Time to diagnosis of AF

Time Frame

At the completion of the event-driven trial, expected 4 years

Title

Time to initiation of OAC

Time Frame

At the completion of the event-driven trial, expected 4 years

Title

Time to adjudicated intracranial hemorrhage not classified as stroke

Time Frame

At the completion of the event-driven trial, expected 4 years

Title

Time to adjudicated hemorrhagic stroke

Time Frame

At the completion of the event-driven trial, expected 4 years

Title

Time to major bleeding as defined by the International Society on Thrombosis and Haemostasis criteria

Time Frame

At the completion of the event-driven trial, expected 4 years

Title

Presence of complications related to loop recorder implantation; infection, hematoma, or other complication related to device implantation requiring intervention

Time Frame

During implantable loop recorder monitoring, expected 3 years

Title

Change from baseline in quality of life

Description

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.

Time Frame

3 years (from baseline to the at the fourth study visit)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

70 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jesper H Svendsen, MD, DMSc

Organizational Affiliation

Rigshospitalet, Denmark

Official's Role

Principal Investigator

Facility Information:

Facility Name

Rigshospitalet

City

Copenhagen

Country

Denmark

12. IPD Sharing Statement

Citations:

PubMed Identifier

22236222

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.

Results Reference

background

PubMed Identifier

26763225

Citation

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.

Results Reference

background

PubMed Identifier

15879330

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. doi: 10.1161/01.STR.0000166053.83476.4a. Epub 2005 May 5.

Results Reference

background

PubMed Identifier

21262990

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.

Results Reference

background

PubMed Identifier

36036546

Citation

Diederichsen SZ, Frederiksen KS, Xing LY, Haugan KJ, Hojberg S, Brandes A, Graff C, Olesen MS, Krieger D, Kober L, Svendsen JH. Severity and Etiology of Incident Stroke in Patients Screened for Atrial Fibrillation vs Usual Care and the Impact of Prior Stroke: A Post Hoc Analysis of the LOOP Randomized Clinical Trial. JAMA Neurol. 2022 Oct 1;79(10):997-1004. doi: 10.1001/jamaneurol.2022.3031. Erratum In: JAMA Neurol. 2022 Oct 17;:

Results Reference

derived

PubMed Identifier

35862138

Citation

Xing LY, Diederichsen SZ, Hojberg S, Krieger DW, Graff C, Olesen MS, Brandes A, Kober L, Haugan KJ, Svendsen JH. Systolic Blood Pressure and Effects of Screening for Atrial Fibrillation With Long-Term Continuous Monitoring (a LOOP Substudy). Hypertension. 2022 Sep;79(9):2081-2090. doi: 10.1161/HYPERTENSIONAHA.122.19333. Epub 2022 Jul 8.

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PubMed Identifier

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Citation

Bonnesen MP, Frodi DM, Haugan KJ, Kronborg C, Graff C, Hojberg S, Kober L, Krieger D, Brandes A, Svendsen JH, Diederichsen SZ. Day-to-day measurement of physical activity and risk of atrial fibrillation. Eur Heart J. 2021 Oct 7;42(38):3979-3988. doi: 10.1093/eurheartj/ehab597.

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Citation

Svendsen JH, Diederichsen SZ, Hojberg S, Krieger DW, Graff C, Kronborg C, Olesen MS, Nielsen JB, Holst AG, Brandes A, Haugan KJ, Kober L. Implantable loop recorder detection of atrial fibrillation to prevent stroke (The LOOP Study): a randomised controlled trial. Lancet. 2021 Oct 23;398(10310):1507-1516. doi: 10.1016/S0140-6736(21)01698-6. Epub 2021 Aug 29. Erratum In: Lancet. 2021 Oct 23;398(10310):1486.

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PubMed Identifier

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Citation

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Citation

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Citation

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Citation

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Results Reference

derived

Links:

URL

http://loop-study.dk

Description

Homepage for the LOOP study

Learn more about this trial

Atrial Fibrillation Detected by Continuous ECG Monitoring

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