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Atrial Fibrillation Detected by Continuous ECG Monitoring (LOOP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Rigshospitalet, Denmark
Sponsor:
Collaborators:
Bispebjerg Hospital
Roskilde Hospital
Odense University Hospital
University of Southern Denmark
Aalborg University
Information provided by (Responsible Party):
Jesper Hastrup Svendsen, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT02036450
First received: January 8, 2014
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

The LOOP study aims to clarify whether stroke and peripheral emboli can be prevented by monitoring the heart rhythm with a small device (called a loop recorder). The recorder which is placed under the skin on the front of the chest wall allows monitoring of the heart rhythm 24-hours a day 7 days a week.

The study has 6,000 participants with risk factors for stroke (age >70 years, and at least one of the diseases: diabetes, hypertension, heart failure or previous stroke) but without a history of atrial fibrillation, of which 1,500 will have a loop recorder implanted and 4,500 will be included in a control group. Participants are randomised to receive a loop recorder or not (control).

If a participant has atrial fibrillation of more than 6 min duration the study participant will start oral anticoagulation therapy according to local guidelines.


Condition Intervention
Atrial Fibrillation
Stroke
Hypertension
Diabetes
Device: LOOP recorder (Medtronic LINQ device)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-risk Individuals.

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Time to stroke or peripheral embolic episode [ Time Frame: 3 years of follow-up (FU) ] [ Designated as safety issue: No ]

    Efficacy (time to at least one of the components of the combined primary endpoint):

    • clinical and adjudicated stroke or
    • clinical and adjudicated peripheral embolic episode

      (i.e. events which presumably can be avoided by a relevant oral anticoagulation (OAC) therapy)



Secondary Outcome Measures:
  • Major bleeding complications [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    Major bleeding complications (according to Schulman and Kearon. Journal of Thrombosis and Haemostasis, 2005; 3: 692-694)

  • death [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    • death due to cardiac reasons/complications
    • death due to any reason

  • cerebral haemorrhage and Transitory Ischaemic Attacks (TIA) [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    Adjudicated events based on brain imaging (CT, MRI).

  • Time to AF, AF burden, and other arrhythmia (bradyarrhythmia and ventricular arrhythmia), [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    Arrhythmia diagnosed by the ILR device or by routine control. In the control group documentation of AF on 12-lead ECG is considered equivalent to an episode of AF with a duration of more than 6 min.

  • Quality of Life (QOL) [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    QOL measurements using validated instruments (SF-36 and the two Euro-Qual survey forms: EQ-5D-3L and EQ-5D-5L respectively)

  • Presence of brain infarcts and white matter hyperintensity on Magnetic Resonance Imaging (MRI; semiquantitative evaluation), [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    Change in occurrence of brain infarcts and white matter hyper-intensity and association with AF and future strokes

  • Health economic costs [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    Changes in the use of healthcare resources and costs, i.e. hospital treatment, general practitioner services, medical specialists, pharmaceuticals, rehabilitation, nursing home and quality-adjusted life-years (QALYs).

  • ECG markers ability of predicting AF [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]

    The association between chronological developments of ECG markers measured from single lead loop recorders and 12-lead ECG and incident AF to identify which patients fall into low or high risk AF groups.

    Relationship between AF burden and development of ECG markers.


  • Acute hospitalisation [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    acute (non-elective) hospitalisation due to cardiac reasons or complications requiring an overnight stay in hospital


Other Outcome Measures:
  • Cardiac chamber dimensions and function as well as fibrosis in chamber walls as assessed by MRI, [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    In a subset of participants we will perform an MRI scan of the heart with Gadolinium contrast to measure chamber dimensions, wall-motion and late enhancement (fibrosis).

  • Safety aspects of device implants, [ Time Frame: 3 years of FU ] [ Designated as safety issue: Yes ]
    Occurrence of infections and hematoma requiring intervention. Need for removal of devices.

  • inflammation markers and association with AF and stroke [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    Inflammatory markers (such as hs-CRP, ILR etc) are elevated in AF and contain prognostic information with future AF history and response to therapy.

  • Genetic prediction of AF and stroke. [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    A large number of Single Nucleoside Polymorphisms (SNPs) are associated with AF. These and others will be studied for associations with stroke.

  • cognitive function [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    cognitive function (using the MOCA instrument)

  • Echocardiographic prediction of AF and stroke [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    Myocardial strain echocardiographic analysis by speckle tracking measurements and tissue doppler echocardiographic variables ability to predict arrhythmic events and stroke

  • Cardiac hormones and serologic risk markers and prediction of events [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]
    P-BNP, p-Troponins and p-creatinine levels and their prediction of AF and Stroke.


Estimated Enrollment: 6000
Study Start Date: January 2014
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ILR group
A LOOP recorder will be implanted. The device sampled arrhythmia information is transmitted to a core facility and evaluated. Data are sent automatically. When AF with a duration of 6 min or more is detected the participant will be advised to start oral anticoagulation therapy according to local preference.
Device: LOOP recorder (Medtronic LINQ device)
A LOOP recorder will be implanted in a 1:3 randomization
No Intervention: Control group
Control group will be followed according to standard care, i.e. in principal by their own GP. The control group will receive an annual phone call for clinical information and a mailed QOL form.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   70 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be eligible for the study subjects must fulfil the following criteria at inclusion:

  • Living address in Region Zealand, Region of Southern Denmark or the Capital Region of Denmark (study subjects from other regions of Denmark who actively contact the study for participation can be included if they wish to participate)
  • 70-90 years of age at the time of screening and in addition the study subject should be clinically evaluated to be biologically a potential candidate for anti-coagulation therapy

and additionally have at least one of the diseases mentioned below:

  • Known diabetes mellitus (type 1 or type 2, with or without medical therapy)
  • History with hypertension with or without a therapy that may reduce blood pressure (i.e., an increased blood pressure at randomization is not required)
  • Heart failure: New York Heart Association (NYHA) class II-IV or a reduced left ventricular ejection fraction (< 0.50).
  • Previous diagnosed stroke (preferably diagnosed in hospital and verified by imaging; previous (TIA, transitory ischemic attack, is not considered an inclusion criterion; a specific time interval from previous stroke to inclusion time is not required) Concerning the four qualifying diseases the study subject is considered qualified for study inclusion if he has a history of one of the diseases (for example subject is now normotensive on life-style correction or medical therapy and similarly if blood glucose has been normalised upon life-style corrections or medical therapy).

Exclusion Criteria:

  • Uncorrected, congenital heart disease or severe valvular stenosis, obstructive cardiomyopathy, active myocarditis, constrictive pericarditis.
  • Recipient of any major organ transplant (e.g. lung, liver, heart or kidney)
  • Receiving or has received 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)
  • Known to be human immunodeficiency virus (HIV) positive with an expected survival of less than 5 years due to HIV infection
  • Renal failure treated with permanent dialysis
  • 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
  • Known atrial fibrillation irrespective of its type (paroxysmal, persistent, long-lasting persistent or permanent)
  • Ongoing therapy with OAC or newer OAC (whereas therapy with platelet inhibitors such as acetyl-salicylic acid, clopidogrel, persantine is not considered as an exclusion)
  • Patients who have a pacemaker (including cardiac resynchronization therapy-pacemaker, CRT-P) or implantable cardioverter defibrillator (ICD), including a Cardiac Resynchronization Therapy defibrillator (CRT-D)
  • Existing contraindication to oral anticoagulation (OAC) therapy
  • On a waiting list for major surgery (cardiac, thoracic or abdominal)
  • Cardiac or thoracic surgery has been performed within 3 months from inclusion
  • Life-expectancy shorter than 6 months
  • Unwillingness to participate or patient does not understand Danish language
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02036450

Contacts
Contact: Jesper H. Svendsen, MD, DMSc (+45) 3545 2735 jesper.hastrup.svendsen@regionh.dk

Locations
Denmark
Rigshospitalet Recruiting
Copenhagen, Denmark
Contact: Jesper Hastrup Svendsen    (+45) 3545 2735    jesper.hastrup.svendsen@regionh.dk   
Sub-Investigator: Lars Køber, MD, DMSc         
Principal Investigator: Søren Højberg, MD, Phd         
Principal Investigator: Axel Brandes, MD, DMSc         
Principal Investigator: Ketil Haugan, MD, Phd         
Sub-Investigator: Derk Krieger, MD, Phd         
Sponsors and Collaborators
Rigshospitalet, Denmark
Bispebjerg Hospital
Roskilde Hospital
Odense University Hospital
University of Southern Denmark
Aalborg University
Investigators
Principal Investigator: Jesper Hastrup Svendsen Rigshospitalet, Denmark
  More Information

Additional Information:
Publications:
Responsible Party: Jesper Hastrup Svendsen, Professor, MD, DMSc, FESC, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02036450     History of Changes
Other Study ID Numbers: H-4-2013-025, 13-135225
Study First Received: January 8, 2014
Last Updated: January 14, 2014
Health Authority: Denmark: Ethics Committee

Keywords provided by Rigshospitalet, Denmark:
atrial fibrillation
cardiac arrhythmia
stroke
implantable loop recorder
bleeding
anticoagulation
hypertension
diabetes
heart failure
mortality

Additional relevant MeSH terms:
Atrial Fibrillation
Stroke
Hypertension
Arrhythmias, Cardiac
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Heart Diseases
Nervous System Diseases
Pathologic Processes
Vascular Diseases

ClinicalTrials.gov processed this record on November 27, 2014