Atrial Fibrillation Detected by Continuous ECG Monitoring

NCT02036450 | Completed DMC

• 2 other identifiers: H-4-2013-02513-135225
• Study Type: interventional
• Target: 6,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Atrial Fibrillation; Stroke; Hypertension; Diabetes

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

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

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

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

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

• Time to adjudicated cardiovascular death

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

• Time to death by any cause

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

Other Outcomes (7)

• Time to diagnosis of AF

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

• Time to initiation of OAC

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

• Time to adjudicated intracranial hemorrhage not classified as stroke

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

Study Arms (2)

ILR group

EXPERIMENTAL

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.

Device: Implantable loop recorder (Medtronic Reveal LINQ(TM))

Control group

NO INTERVENTION

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.

Interventions

Implantable loop recorder (Medtronic Reveal LINQ(TM)) DEVICE

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.

ILR group

Eligibility Criteria

• Age: 70 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• History of atrial fibrillation or flutter irrespective of type
• Cardiac pacemaker or defibrillator (with or without re-synchronization therapy)
• Contraindication to oral anticoagulation therapy
• 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)
• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Bispebjerg Hospital: collaborator
• Zealand University Hospital: collaborator
• Odense University Hospital: collaborator
• University of Southern Denmark: collaborator
• Aalborg University: collaborator

Study Sites (1)

Rigshospitalet

Copenhagen, Denmark

Location

Related Publications (18)

• 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.

  PMID: 22236222 BACKGROUND

• 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.

  PMID: 26763225 BACKGROUND

• 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.

  PMID: 15879330 BACKGROUND

• 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.

  PMID: 21262990 BACKGROUND

• Kongebro EK, Kronborg C, Haugan KJ, Graff C, Hojberg S, Krieger D, Brandes A, Kober L, Svendsen JH, Diederichsen SZ. The impact of screening-detected atrial fibrillation and associated outcomes on quality of life. Qual Life Res. 2025 Dec;34(12):3597-3608. doi: 10.1007/s11136-025-04047-1. Epub 2025 Aug 31.

  PMID: 40886243 DERIVED

• Xing LY, Hojberg S, Kriegerg DW, Graff C, Olesen MS, Healey JS, McIntyre WF, Brandes A, Kober L, Haugan KJ, Svendsen JH, Diederichsen SZ. Heart Failure Events After Long-term Continuous Screening for Atrial Fibrillation: Results From the Randomized LOOP Study. Circ Arrhythm Electrophysiol. 2024 Aug;17(8):e012764. doi: 10.1161/CIRCEP.124.012764. Epub 2024 Jul 18.

  PMID: 39022823 DERIVED

• Olsen FJ, Diederichsen SZ, Jorgensen PG, Jensen MT, Dahl A, Landler NE, Graff C, Brandes A, Krieger D, Haugan K, Kober L, Hojberg S, Svendsen JH, Biering-Sorensen T. Left Atrial Strain Predicts Subclinical Atrial Fibrillation Detected by Long-term Continuous Monitoring in Elderly High-Risk Individuals. Circ Cardiovasc Imaging. 2024 Mar;17(3):e016197. doi: 10.1161/CIRCIMAGING.123.016197. Epub 2024 Mar 5.

  PMID: 38440875 DERIVED

• Xing LY, Diederichsen SZ, Hojberg S, Krieger DW, Graff C, Frikke-Schmidt R, Platonov PG, Olesen MS, Brandes A, Kober L, Haugan KJ, Svendsen JH. The ABC-Stroke Risk Score and Effects of Atrial Fibrillation Screening on Stroke Prevention: Results From the Randomized LOOP Study. J Am Heart Assoc. 2024 Feb 20;13(4):e032744. doi: 10.1161/JAHA.123.032744. Epub 2024 Feb 14.

  PMID: 38353260 DERIVED

• Xing LY, Diederichsen SZ, Hojberg S, Krieger DW, Graff C, Frikke-Schmidt R, Olesen MS, Brandes A, Kober L, Haugan KJ, Svendsen JH. Effects of Atrial Fibrillation Screening According to N-Terminal Pro-B-Type Natriuretic Peptide: A Secondary Analysis of the Randomized LOOP Study. Circulation. 2023 Jun 13;147(24):1788-1797. doi: 10.1161/CIRCULATIONAHA.123.064361. Epub 2023 Apr 15.

  PMID: 37061802 DERIVED

• 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.

  PMID: 36036546 DERIVED

• 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.

  PMID: 35862138 DERIVED

• 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.

  PMID: 34471928 DERIVED

• 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.

  PMID: 34469766 DERIVED

• Bertelsen L, Diederichsen SZ, Haugan KJ, Brandes A, Graff C, Krieger D, Kronborg C, Kober L, Peters DC, Olesen MS, Hojberg S, Vejlstrup N, Svendsen JH. Left Atrial Late Gadolinium Enhancement is Associated With Incident Atrial Fibrillation as Detected by Continuous Monitoring With Implantable Loop Recorders. JACC Cardiovasc Imaging. 2020 Aug;13(8):1690-1700. doi: 10.1016/j.jcmg.2020.03.024. Epub 2020 Jun 17.

  PMID: 32563642 DERIVED

• Diederichsen SZ, Haugan KJ, Kronborg C, Graff C, Hojberg S, Kober L, Krieger D, Holst AG, Nielsen JB, Brandes A, Svendsen JH. Comprehensive Evaluation of Rhythm Monitoring Strategies in Screening for Atrial Fibrillation: Insights From Patients at Risk Monitored Long Term With an Implantable Loop Recorder. Circulation. 2020 May 12;141(19):1510-1522. doi: 10.1161/CIRCULATIONAHA.119.044407. Epub 2020 Mar 2.

  PMID: 32114796 DERIVED

• Diederichsen SZ, Haugan KJ, Brandes A, Lanng MB, Graff C, Krieger D, Kronborg C, Holst AG, Kober L, Hojberg S, Svendsen JH. Natural History of Subclinical Atrial Fibrillation Detected by Implanted Loop Recorders. J Am Coll Cardiol. 2019 Dec 3;74(22):2771-2781. doi: 10.1016/j.jacc.2019.09.050.

  PMID: 31779791 DERIVED

• Olsen FJ, Svendsen JH, Kober L, Hojberg S, Haugan K, Jensen JS, Biering-Sorensen T. Impact of transducer frequency setting on speckle tracking measures. Int J Cardiovasc Imaging. 2018 Mar;34(3):457-463. doi: 10.1007/s10554-017-1254-4. Epub 2017 Nov 3.

  PMID: 29101521 DERIVED

• Bertelsen L, Svendsen JH, Kober L, Haugan K, Hojberg S, Thomsen C, Vejlstrup N. Flow measurement at the aortic root - impact of location of through-plane phase contrast velocity mapping. J Cardiovasc Magn Reson. 2016 Sep 7;18(1):55. doi: 10.1186/s12968-016-0277-7.

  PMID: 27599727 DERIVED

Related Links

• Homepage for the LOOP study

MeSH Terms

Conditions

Atrial Fibrillation; Stroke; Hypertension; Diabetes Mellitus; Arrhythmias, Cardiac; Hemorrhage; Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Jesper H Svendsen, MD, DMSc

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, DMSc, FESC

Study Record Dates

• First Submitted: January 8, 2014
• First Posted: January 15, 2014
• Study Start: January 1, 2014
• Primary Completion: February 1, 2020
• Study Completion: March 1, 2021
• Last Updated: March 10, 2021

Record last verified: 2021-03

Locations

DK (1)