ClinicalTrials.gg
CompletedNCT02684825SAFFOUpdated Jun 29, 2023

Detection of Silent Atrial Fibrillation aFter Ischemic StrOke

An interventional study of Reveal LINQTM- LNQ11 Internal Loop Recorder plus standard cardiac monitoring in Ischemic Stroke, Cerebral Infarction and Brain Ischemia, sponsored by Danilo Toni. Completed at 1 site in Italy. Open to participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2023-06-29.

Sponsored by Danilo Toni · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
317
Allocation
Randomized
Ages
65 Years and older
Sex
All
01

Study summary

The primary objective of this study is to evaluate whether, in patients with first-ever atherothrombotic or lacunar stroke without any previous history of atrial fibrillation (AF)/atrial flutter (AFL)/atrial tachycardia (AT), the detection of AF/AFL/AT (silent or symptomatic) by using a continuous cardiac rhythm monitoring with implantable loop recorder (ILR) during the first 12 months of observation is higher than the detection by using a standard cardiac monitoring (physical exam, 12-lead electrocardiogram [ECG] at baseline, 3, 6, and 12 months and Holter ECG at 3 months) in the same period of time.

Read the detailed description

Atrial fibrillation (AF) is associated with a high risk of stroke and its prevalence increases in subjects aged ≥65 years. After an ischemic stroke, the use of standard monitoring methods may underestimate the detection rate of AF. Recent studies demonstrated a fourfold to sixfold increase in the detection of AF with prolonged ECG monitoring as compared to standard cardiac monitoring in patients with cryptogenic stroke. Hence, it is very likely that even patients having a first atherothrombotic or lacunar stroke with high burden of vascular risk factors are exposed to increased risk of developing AF in the subsequent years and AF may be the cause underlying possible recurrent strokes.

SAFFO trial has the objective to evaluate the detection of AF or atrial flutter (AFL) as first diagnosis by implantable loop recorder (ILR) in patients with first-ever atherothrombotic or lacunar stroke. Patients with recent (30-60 days after symptom onset) diagnosis of first-ever atherothrombotic or lacunar ischemic stroke who fulfill inclusion criteria will be randomized to either continuous cardiac monitoring using an ILR plus standard cardiac monitoring (intervention arm) or standard cardiac monitoring alone (control arm) with a ratio of 1:1. The hypothesis is that the detection of of AF/AFL by using ILR will be higher than that observed by using standard cardiac monitoring. Secondary and tertiary objectives of the study include exploratory analyses on the incidence of recurrent strokes and different stroke subtypes and on the reduction of stroke risk and death from all causes in all study patients, in the two randomization groups and, in particular, in patients treated with antiplatelet therapy versus those treated with oral anticoagulant (OAC) therapy, the latter being implemented and guided by the detection of clinically meaningful episodes of AF/AFL/AT using ILR compared with standard cardiac monitoring. Moreover, this study has the objective to evaluate a clinical, neuroimaging, and echocardiographic profile predictive of AF/AFL/AT first diagnosis and stroke recurrence.

SAFFO is a prospective, multicenter, randomized, controlled, open-label trial with blinded assessment of outcome measures. Diagnosis of atherothrombotic and lacunar etiology will be defined according to TOAST (trial of ORG 10172 in acute stroke treatment) / CCS (Causative Classification System for ischemic stroke) classification criteria and standard diagnostic protocols that have to be fulfilled before randomization (medical history; risk factors; symptoms; cerebral magnetic resonance [MR] and/or CT; 12-lead ECG and/or Holter ECG and/or other standard heart rhythm monitoring procedure; transthoracic and/or transoesophageal echocardiogram; intra- and extracranial vessel ultrasonography and/or CT-Angiography and/or MR- Angiography, also in order to rule out non-atherosclerotic vasculopathies; thrombophilic/hematologic screening if hypercoagulability states or other hematologic disorders are suspected).

ILR (Medtronic Reveal LINQTM- LNQ11REVEAL LinQ) implantation will be performed within 8 days after randomization and will allow a continuous monitoring by single-lead ECG registration for 3 years. Standard cardiac rhythm monitoring includes: detailed data collection on any possible patient's symptom suggestive of AF/AFL/AT, physical exam including cardiovascular examination, 12-lead ECG, and 24-hour Holter ECG performed at 3-month follow-up visit.

If positive, SAFFO trial could have important clinical implications in terms of changing the standard diagnostic protocol in patients with atherothrombotic and lacunar stroke, and of increasing the shift of secondary prevention treatment from antiplatelet to anticoagulant therapy when indicated.

02

Conditions studied

  • Ischemic Stroke
  • Cerebral Infarction
  • Brain Ischemia
  • Brain Infarction
  • Cerebrovascular Disorders
  • Brain Disease
  • Central Nervous System Diseases
  • Nervous System Diseases
  • Cardiac Arrhythmias

Keywords

  • Stroke
  • ischemic stroke
  • atrial fibrillation
  • continuous cardiac monitoring
  • insertable cardiac monitoring
  • implantable loop recorder
  • antithrombotics
  • anticoagulants
  • stroke subtype
  • atherothrombotic stroke
  • lacunar stroke
03

In context

Ischemic Stroke

2,612 studies on the registry are indexed under Ischemic Stroke; 971 are open to participants now.

This study's enrollment of 317 is above the median of 120 across 1,776 interventional studies indexed under Ischemic Stroke.

Browse Ischemic Stroke studies →

Lead sponsor

This is the only study on the registry with Danilo Toni as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
65 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Age ≥65 years old in the presence of at least one of the following vascular risk factors: hypertension; diabetes; vascular disease (previous myocardial infarction, peripheral arteriopathy).
  • Age between 60 and 64 years old in the presence of at least two of the following vascular risk factors: hypertension; diabetes; vascular disease (previous myocardial infarction, peripheral arteriopathy); smoking.
  • Recent (30-60 days after symptom onset) diagnosis of first-ever ischemic stroke. Ischemic stroke is defined as an event characterized by the sudden onset of acute focal neurological symptoms, MR or CT findings consistent with ischemic stroke, and no evidence of other neurological disorders clinically or radiographically to explain. Patients with reversible neurological deficit within 24 hours (clinical ), but with a cerebral injury of ischemic origin visible on neuroimages and corresponding to patient symptoms, have to be classified as having an ischemic stroke and considered for the study.
  • Diagnosis of atherothrombotic and lacunar etiology, defined according to the TOAST classification criteria and standard diagnostic protocols that have to be fulfilled before randomization (medical history; risk factors; symptoms; cerebral MR and/or CT; 12-lead and/or Holter ECG and/or other standard heart rhythm monitoring procedure; transthoracic and/or transoesophageal echocardiogram; intra- and extracranial vessel ultrasonography and/or CT-Angiography and/or MR-Angiography, also in order to rule out non-atherosclerotic vasculopathies; thrombophilic/hematologic screening if hypercoagulability states or other hematologic disorders are suspected).
  • Neurological severity in terms of functional dependency defined as mRS (modified Rankin Scale) score ≤3.
  • Written .

Exclusion criteria

Exclusion Criteria:

  • without evidence of cerebral infarction on neuroimaging corresponding to patient symptoms.
  • Diagnosis of cardioembolic stroke based on medical history and cerebral/cardiological/vascular diagnostic evaluation (e.g., evidence of a high-risk emboligenic source from the heart or aortic arch such as: left ventricle or atrium thrombus or "smoke", emboligenic valvular lesions, or emboligenic tumor, patent foramen ovale [PFO] associated with a possible venous thromboembolic source and hence eligible for oral anticoagulant [OAC] therapy, aortic arch plaques having >3 mm thickness or containing mobile components, or any other high-risk embolic lesion).
  • Diagnosis of ischemic stroke of different etiopathogenesis, for example due to non-atherosclerotic vasculopathies, hypercoagulability states (diagnosed by a thrombophilic screening) or other hematologic disorders; or diagnosis of cryptogenic stroke.
  • Previous documented history of atrial fibrillation (AF) or atrial flutter (AFL)
  • History of untreated hyperthyroidism
  • History of myocardial infarction \<1 month before the study screening visit
  • Valvular disease requiring immediate surgical intervention
  • Recent (\<6 months before the study screening visit) cardiac surgery
  • Other conditions associated with an increased risk of AF: sick sinus syndrome, recent (\<14 days before the study Screening visit) surgery; current infections
  • Permanent indication for anticoagulation
  • to OAC therapy
  • Stroke associated with severe functional disability defined as mRS>3
  • Hear failure associated with severe ventricular dysfunction and ≤40%
  • Indication for pacemaker or defibrillator implant
  • Any condition that, in the opinion of the investigator, could make non feasible or hazardous patient's participation in the study or any condition that could compromise the completion of patient's participation in terms of follow-up visits (for example, diseases associated with a poor prognosis and \<1 year).
  • Severe renal failure or liver disease
  • Participation in any other clinical trial that can interfere with the objectives of the study
  • Poor patient's compliance that could compromise his/her correct participation in the study
  • Patient's refusal to give his/her for the participation in the study.
Terms in these criteria, in plain language(6)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

TIA (transient ischaemic attack)

A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.

Stroke symptoms need emergency care at once, even if they go away.

ECG (electrocardiogram)

A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

LVEF (left ventricular ejection fraction)

The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

05

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
317 participants (actual)

Study arms

  • Experimental
    Continuous plus standard cardiac monitoring

    Continuous cardiac monitoring by Reveal LINQTM- LNQ11 Internal Loop Recorder (ILR) plus standard cardiac monitoring

    Device: Reveal LINQTM- LNQ11 Internal Loop Recorder plus standard cardiac monitoring

  • No intervention
    Standard cardiac monitoring

    Routine cardiac monitoring with follow-up at the same frequency, but with no Implantable Loop Recorder

Interventions

  • DeviceReveal LINQTM- LNQ11 Internal Loop Recorder plus standard cardiac monitoring

    Reveal LINQTM- LNQ11 continuously monitors cardiac electric activity for up to three years.

    Also known as: Reveal LINQTM- LNQ11

06

What researchers measure

Primary outcomes

  1. Detection rate of AF/AFL/AT within 12 months

    Episodes of AF/AFL/AT will be adjudicated by an independent committee of cardiologists blinded to randomization arm

    Time frame: 12 months

Secondary outcomes

  1. Incidence of ischemic stroke recurrence and incidence of the different ischemic stroke subtypes

    Stroke subtypes will be adjudicated by an independent committee of neurologists blinded to randomization arm

    Time frame: 36 months

  2. Reduction of the risk of ischemic stroke and death from all causes

    Reduction of the risk of ischemic stroke and death from all causes will be evaluated in particular in patients treated with antiplatelet therapy versus those treated with OAC therapy, the latter being implemented and guided by the detection of clinically meaningful episodes of AF/AFL/AT using ILR compared with standard cardiac monitoring

    Time frame: 36 months

Other outcomes

  1. Rate of asymptomatic/symptomatic episodes of AF/AFL/AT

    Time frame: 36 months

  2. Use of oral anticoagulant (OAC) drugs

    Percentage of subjects who will use OAC drugs at the 36-month follow-up visit

    Time frame: 36 months

  3. Use of antiarrhythmic drugs

    Percentage of subjects who will use antiarrhythmic drugs at the 36-month follow-up visit

    Time frame: 36 months

  4. Time from AF/AFL/AT detection to the change of secondary prevention treatment from antiplatelet to OAC therapy

    Time frame: 36 months

  5. Burden of AF/AFL/AT and relative clinical, imaging, and treatment associations

    Time frame: 36 months

  6. Progression of the cerebrovascular damage

    Progression of cerebrovascular damage will be evaluated in terms of increase of silent infarct number, leukoaraiosis/white matter hyperintensity, microbleeds, dilated perivascular spaces, and brain atrophy measured on MR

    Time frame: 36 months

  7. Progression of possible cognitive impairment

    Minimental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) are scales that will be used to measure cognitive functions

    Time frame: 36 months

  8. Health outcome as evaluated by ED-5D-3L Questionnaire

    EQ-5D-3L (visual analog scale, VAS) quality of life score is a continuous measure of quality of life ranging from 0 (worst) to 100 (perfect health)

    Time frame: 36 months

07

Study locations

1 site
  • Azienda Policlinico Umberto I
    Rome, 00161, Italy
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 29, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT02684825
Lead sponsor
Danilo Toni
Collaborators
Associazione Italiana Aritmologia e Cardiostimolazione (A.I.A.C.) - Stefano Strano, MD, Boehringer Ingelheim, Medtronic Italia S.p.A., Bayer S.p.A
Responsible party
Danilo Toni (Director, Emergency Department Stroke Unit - Associate Professor of Neurology, Azienda Policlinico Umberto I) — Sponsor-investigator
First posted
Feb 18, 2016
Start date
Oct 2015
Primary completion
May 31, 2022
Completion
May 31, 2022
Last update
Jun 29, 2023

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jun 2023. You cannot join it, but the record below documents what was studied.

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