Key Results
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
BIOSync CLS Clinical Trial
Cardiac Pacing in Severe Recurrent Reflex Syncope and Tilt-Induced Asystole
Brignole M, Russo V, Arabia F, Oliveira M, Pedrote A, Aerts A, Rapacciuolo A, Boveda S, Deharo JC, Maglia G, Nigro G, Giacopelli D, Gargaro A, Tomaino M; BioSync CLS trial Investigators. Cardiac pacing in severe recurrent reflex syncope and tilt-induced asystole. Eur Heart J. 2021 Feb 1;42(5):508-516.
Study Design
- 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 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
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 Details
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