BioSync CLS

BIOSync CLS

Cardiac Pacing in Severe Recurrent Reflex Syncope and Tilt-Induced Asystole

 


Study Design

 

For more information about this study

  • Randomized, placebo-controlled, prospective, double blinded, international, multicenter clinical trial    
  • Patients with severe reflex syncopies and previously implanted Eluna/Epyra 8 DR-T devices
  • 1:1 randomized to DDD-CLS pacing vs. ODO mode (placebo; no pacing , dual chamber sensing only)
  • Patients  and Clinical Events Adjudication Committee were blinded to pacing mode
  • Quarterly self-administered patient questionnaire to collect study endpoints
  • Sequential study design with two interim analyses at 40% and 70% of the required endpoints

 

Key Result 1

CLS significantly reduced the syncope recurrence rate by 77% versus placebo

 

Figure 1: Survival free of syncope recurrence for CLS-paced patients versus placebo

Imagen

Key Result 2

CLS significantly reduced the combined rate of syncope and/or pre-syncope by 56% versus placebo

 

Figure 2: Survival free of recurrence of syncope/pre-syncope for CLS-paced patients versus placebo

Imagen

Clinical Relevance

  • The BIOSync CLS study is the largest and best–designed randomized clinical trial to demonstrate the efficacy of cardiac pacing with CLS in patients suffering from severe recurrent reflex syncope
  • So far, the usefulness of tilt-table testing to select patients with severe recurrent reflex syncope for cardiac pacing was controversial. The positive results of the BioSync CLS study indicate that asystolic response to tilt-table tests is a valuable selection criterion.
  • By using a physiologic signal retrieved from the body’s own cardiovascular regulation, Closed Loop Stimulation is able to provide clinical benefit beyond physiological pacing therapy of chronotropic incompetent patients.

 


Study Objective
  • To assess the efficacy of Closed Loop Stimulation (CLS) in preventing syncopal recurrences and the usefulness of an asystolic response during tilt testing to identify responders to cardiac pacing
Primary Endpoint
  • Time to first post-randomization recurrence of a syncopal episode  
    (= transient complete loss of consciousness characterized by rapid onset, short duration, and spontaneous complete recovery)

Major Secondary Endpoints
  • Time to first recurrence of a syncopal or a pre-syncopal episode, whichever comes first
Clinical Sites
  • 24 (Italy, France, Spain, Portugal, Netherlands, and Canada)
Sample Size
  • 127 patients
Main Inclusion Criteria
  • Patients with severe reflex syncopies
  • ≥ 40 years of age
  • ≥ 2 episodes in the last year
  • Tilt table-induced syncope with asystolic pause > 3 seconds
  • Alternate therapies have failed or were not feasibile
  • Exclusion of other possible competitive causes of syncope

Main Exclusion Criteria
  • Any other indication to pacemaker, ICD or cardiac resynchronization therapy according to current guidelines    
  • Any cardiac dysfunctions possibly leading to loss of consciousness    
  • Symptomatic orthostatic hypotension diagnosed by standing blood pressure measurement
  • Non-syncopal loss of consciousness (e.g., epilepsy, cerebral transient ischemic attack, intoxication, cataplexy)
  • Symptomatic cardio-inhibitory carotid sinus hypersensitivity
Study Flowchart
Follow-Up
  • 24 months
Study Duration
  •  Following the second interim analysis, the study was prematurely terminated due to evident superiority of the results in the treatment arm.
Reference no.
  • Reference no.    NCT02324920
    Eudamed number CIV-05-013546

     

Principal Investigators
  • Brignole M., Ospedale San Luca, Milano, Italy