Atrial Fibrillation Detected by Continuous ECG Monitoring (LOOP)
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.
Device: LOOP recorder (Medtronic LINQ device)
|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.|
- 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)
- Composite endpoint of time to stroke or peripheral embolic episode or death [ Time Frame: 3 years of FU ] [ Designated as safety issue: No ]Efficacy (time to at least one of the components of the endpoints)
- 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). Cost-effectviveness analysís - and evaluation of the instrument EQ-5D.
- 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
- 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.
|Study Start Date:||January 2014|
|Estimated Study Completion Date:||April 2019|
|Estimated Primary Completion Date:||April 2019 (Final data collection date for primary outcome measure)|
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT02036450
|Contact: Jesper H. Svendsen, MD, DMSc||(+45) 3545 email@example.com|
|Contact: Jesper Hastrup Svendsen (+45) 3545 2735 firstname.lastname@example.org|
|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|
|Principal Investigator:||Jesper Hastrup Svendsen||Rigshospitalet, Denmark|