SyncopeBIO|Sync-HUTTNCT06038708
Head-up Tilt Test in Patients With Reflex Syncope and Asystolic Response Who Received a Dual-chamber Pacemaker With the Closed Loop Stimulation (CLS) and Participated in the BIOSync Trial
An observational study of Syncope and Syncope, Vasovagal, run by Biotronik SE & Co. KG at 2 sites in Italy.
Trial summary
The purpose of this study is to explore changes in patients' hemodynamic parameters during the Head-Up Tilt Test ("HUTT") and their timing with respect to onset of the Closed Loop Stimulation (CLS) pacing. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Syncope, Syncope, Vasovagal
- How many people
- 20 participants
- Where
- 2 sitesItaly
- Study dates
- 29 Sep 2022to 12 May 2023
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with reflex syncope and positive cardioinhibitory response to Head-Up Tilt Test (HUTT) who had already participated in the BIOSync study.
Who may be able to join
- Ability to understand the nature of the study.
- Willingness to provide written informed consent.
- Patients undergoing HUTT for monitoring of syncope, therapy adjustment, training or other medical reasons during ordinary follow-up, irrespective of study participation
- Patients who participated in the BIOSync study*.
- Patients with a dual-chamber pacing system equipped with the CLS algorithm. * If needed, inclusion of other patients who did not participate in the BIOSync study will be considered to complete study cohort, provided that they have already a CLS pacemaker system and fulfill the same inclusion/exclusion criteria of the BIOSync study.
Who cannot join
- Pregnant or breast feeding women.
- Age less than 40 years.
- Patients who after the BIOSync study participation have developed the following:
- Any indication to pacemaker different from reflex syncope with positive HUTT response; or
- Any classified indication to implantable defibrillator, cardiac resynchronization therapy according to current guidelines; or
- Any cardiac dysfunctions likely leading to loss of consciousness (overt heart failure, ejection fraction <40%, myocardial infarction, diagnosis of hypertrophic or dilated cardiomyopathy, clinically significant valvular disease, sinus bradycardia <50 bpm or sinoatrial block, Mobitz I second degree atrioventricular block, Mobitz II second or third degree atrioventricular block, complete bundle-branch block).
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Ospedale di Bolzano - Azienda Sanitaria dell'Alto Adige
Bolzano, 39100
Monaldi - AORN dei Colli - Università della Campania "Luigi Vanvitelli"
Naples, 80131
About this study
Official title: BIO|Sync-HUTT: Head-up Tilt Test in Patients With Reflex Syncope and Asystolic Response Who Received a Dual-chamber Pacemaker With the Closed Loop Stimulation (CLS) and Participated in the BIOSync Trial
The purpose of this study is to explore changes in patients' hemodynamic parameters during the Head-Up Tilt Test ("HUTT") and their timing with respect to onset of the Closed Loop Stimulation (CLS) pacing. This study aims to add knowledge to better understand the mechanisms underlying recurrent syncopal events and optimal pacing programming.
Read the detailed description
The 2021 European Society of Cardiology guidelines recommend cardiac pacing in patients aged >40 years with tilt-induced asystolic reflex syncope (class I, level of evidence A). The recommendation relies on recent results from the multicentre, randomised, double-blinded, parallel-design BIOSync trial (NCT02324920). The BIOSync study provided evidence of benefit of dual chamber pacing in patients with tilt-induced reflex syncope and confirmed the role of Head-up Tilt Table (HUTT) test as a diagnostic method for cardiac pacing in reflex syncope. The Closed Loop Stimulation (CLS) is able to measure changes in intracardiac impedance during the systolic phase of each cardiac cycle which are strictly correlated to the increased heart rate and right ventricular contraction speed which are usually present during the pre-syncope phase of the reflex. It was hypothesized that an early onset of CLS pacing may be triggered by the compensatory increase in heart rate to counteract vasodilation and pressure drop during the pre-syncope phase of the reflex. The BIOSync study showed a 77% reduced risk of syncope in the DDD-CLS group as compared to pacing off. The design of the BIOSync study did not allow to assess the specific effect that CLS adds to dual-chamber pacing. Despite DDD-CLS pacing, 22% of patients had syncopal recurrence in 2 years. Further investigations are therefore needed in order to reduce this failure rate. Indeed, it is still unclear whether syncopal recurrences should be ascribed to dominant vasodilation or if the CLS programming/functioning needs optimization to more adequately sustain cardiac output during reflex in these specific cases.
- Conditions
- Syncope, Syncope, Vasovagal
- Keywords
- Syncope, Head-up Tilt Test, Closed Loop Stimulation, CLS
- Medical subject headings
- Syncope, Syncope, Vasovagal
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart Rate [Bpm] at Specific Time-points During Head-up Tilt Test (HUTT) Examination
Instantaneous measurement of heart rate value at specific time-points/stages during HUTT examination. Changes in Heart rate were investigated across four stages of the HUTT: baseline (Stage 1), pre-syncopal phase (Stage 2), maximum heart rate/pacing rate (Stage 3), and syncope or lowest Systolic Blood Pressure (Stage 4).
Measured: From the start to the end of the HUTT examination, assessed up to 45 minutes
Systolic Blood Pressure at Specific Time-points During Head-up Tilt Test (HUTT) Examination
Instantaneous measurement of blood pressure at specific time-points during HUTT examination. Changes in Systolic blood pressure were investigated across four stages of the HUTT: baseline (Stage 1), pre-syncopal phase (Stage 2), maximum heart rate/pacing rate (Stage 3), and syncope or lowest Systolic Blood Pressure (Stage 4).
Measured: From the start to the end of the HUTT examination, assessed up to 45 minutes
Stroke Volume [ml] at Specific Time-points During Head-up Tilt Test (HUTT)
Instantaneous measurement of stroke volume at specific time-points during HUTT examination
Measured: From the start to the end of the HUTT examination, assessed up to 45 minutes
Peripheral Resistance [Dyn·s/cm5] at Specific Time-points During Head-up Tilt Test (HUTT)
Instantaneous measurement of peripheral resistance at specific time-points during HUTT examination
Measured: From the start to the end of the HUTT examination, assessed up to 45 minutes
Time of Maximum Spontaneous Heart Rate
Recording of a specific time-point during HUTT examination. This time was collected as hours:minutes:seconds (e.g. 00:35:34).
Measured: From the start to the end of the HUTT examination, assessed up to 45 minutes
Time of Pacing Onset
Recording of a specific time-point during HUTT examination. This time was collected as hours:minutes:seconds (e.g. 00:35:34).
Measured: From the start to the end of the HUTT examination, assessed up to 45 minutes
Time of Recovery of Spontaneous Rhythm After Pacing
Recording of a specific time-point during HUTT examination. This time was collected as hours:minutes:seconds (e.g. 00:35:34).
Measured: From the start to the end of the HUTT examination, assessed up to 45 minutes
Time of Syncope
Recording of a specific time-point during HUTT examination. This time was collected as hours:minutes:seconds (e.g. 00:35:34).
Measured: From the start to the end of the HUTT examination, assessed up to 45 minutes
Time of Tilt-down
Recording of a specific time-point during HUTT examination. This time was collected as hours:minutes:seconds (e.g. 00:35:34).
Measured: From the start to the end of the HUTT examination, assessed up to 45 minutes
Duration of the Recovery Phase [Minutes]
Interval from maximum pacing rate to basic rate or spontaneous rhythm
Measured: From the start to the end of the HUTT examination, assessed up to 45 minutes
Slope in Heart Rate [Bpm/Minute] During the Recovery Phase
Calculation of the rate of change of heart rate from the time of maximum pacing rate to the time of basic rate or spontaneous rhythm recovery
Measured: From the start to the end of the HUTT examination, assessed up to 45 minutes
Slope in Systolic Blood Pressure (mmHg Per Minute) During the Recovery Phase
Calculation of the rate of change of systolic blood pressure from the time of maximum pacing rate to the time of basic rate or spontaneous rhythm recovery
Measured: From the start to the end of the HUTT examination, assessed up to 45 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2023
- Study start29 Sep 2022
- Primary completion12 May 2023
- Study completion12 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SyncopeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- Biotronik SE & Co. KG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06038708
- Sponsor's protocol ID
- BA117
- Acronym
- BIO|Sync-HUTT
- Status last verified
- Oct 2024
- First submitted
- 1 Sep 2023
- Last updated
- 3 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be shared on request to the corresponding author with permission of BIOTRONIK SE \& Co. KG.
Publications
Russo V, Tomaino M, Parente E, Comune A, Giacopelli D, Napoli P, Gargaro A, Brignole M. Temporal relationship between haemodynamic changes and activation of closed-loop stimulation during a tilt-induced vasovagal syncope. Europace. 2024 Feb 1;26(2):euae045. doi: 10.1093/europace/euae045.
PubMed 38340330
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BIO|Sync-HUTT: Head-up Tilt Test in Patients With Reflex Syncope and Asystolic Response Who Received a Dual-chamber Pacemaker With the Closed Loop Stimulation (CLS) and Participated in the BIOSync Trial
- ClinicalTrials.gov ID
- NCT06038708
- Acronym / sponsor ID
- BIO|Sync-HUTT / BA117
- Conditions
- Syncope, Syncope, Vasovagal
- Keywords
- Syncope, Head-up Tilt Test, Closed Loop Stimulation, CLS
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Biotronik SE & Co. KGIndustry (pharma, biotech, devices)
- Study start
- 29 Sep 2022 (actual)
- Primary completion
- 12 May 2023 (actual)
- Study completion
- 12 May 2023 (actual)
- First posted
- 15 Sep 2023 (actual)
- Results
- Posted 3 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to explore changes in patients' hemodynamic parameters during the Head-Up Tilt Test ("HUTT") and their timing with respect to onset of the Closed Loop Stimulation (CLS) pacing. This study aims to add knowledge to better understand the mechanisms underlying recurrent syncopal events and optimal pacing programming.
Detailed description
The 2021 European Society of Cardiology guidelines recommend cardiac pacing in patients aged >40 years with tilt-induced asystolic reflex syncope (class I, level of evidence A). The recommendation relies on recent results from the multicentre, randomised, double-blinded, parallel-design BIOSync trial (NCT02324920). The BIOSync study provided evidence of benefit of dual chamber pacing in patients with tilt-induced reflex syncope and confirmed the role of Head-up Tilt Table (HUTT) test as a diagnostic method for cardiac pacing in reflex syncope. The Closed Loop Stimulation (CLS) is able to measure changes in intracardiac impedance during the systolic phase of each cardiac cycle which are strictly correlated to the increased heart rate and right ventricular contraction speed which are usually present during the pre-syncope phase of the reflex. It was hypothesized that an early onset of CLS pacing may be triggered by the compensatory increase in heart rate to counteract vasodilation and pressure drop during the pre-syncope phase of the reflex. The BIOSync study showed a 77% reduced risk of syncope in the DDD-CLS group as compared to pacing off. The design of the BIOSync study did not allow to assess the specific effect that CLS adds to dual-chamber pacing. Despite DDD-CLS pacing, 22% of patients had syncopal recurrence in 2 years. Further investigations are therefore needed in order to reduce this failure rate. Indeed, it is still unclear whether syncopal recurrences should be ascribed to dominant vasodilation or if the CLS programming/functioning needs optimization to more adequately sustain cardiac output during reflex in these specific cases.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Day
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with reflex syncope and positive cardioinhibitory response to Head-Up Tilt Test (HUTT) who had already participated in the BIOSync study.
Key inclusion criteria (5 listed)
- Ability to understand the nature of the study.
- Willingness to provide written informed consent.
- Patients undergoing HUTT for monitoring of syncope, therapy adjustment, training or other medical reasons during ordinary follow-up, irrespective of study participation
- Patients who participated in the BIOSync study*.
- Patients with a dual-chamber pacing system equipped with the CLS algorithm. * If needed, inclusion of other patients who did not participate in the BIOSync study will be considered to complete study cohort, provided that they have already a CLS pacemaker system and fulfill the same inclusion/exclusion criteria of the BIOSync study.
Key exclusion criteria (6 listed)
- Pregnant or breast feeding women.
- Age less than 40 years.
- Patients who after the BIOSync study participation have developed the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Heart Rate [Bpm] at Specific Time-points During Head-up Tilt Test (HUTT) Examination
Time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
Instantaneous measurement of heart rate value at specific time-points/stages during HUTT examination. Changes in Heart rate were investigated across four stages of the HUTT: baseline (Stage 1), pre-syncopal phase (Stage 2), maximum heart rate/pacing rate (Stage 3), and syncope or lowest Systolic Blood Pressure (Stage 4).
Systolic Blood Pressure at Specific Time-points During Head-up Tilt Test (HUTT) Examination
Time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
Instantaneous measurement of blood pressure at specific time-points during HUTT examination. Changes in Systolic blood pressure were investigated across four stages of the HUTT: baseline (Stage 1), pre-syncopal phase (Stage 2), maximum heart rate/pacing rate (Stage 3), and syncope or lowest Systolic Blood Pressure (Stage 4).
Stroke Volume [ml] at Specific Time-points During Head-up Tilt Test (HUTT)
Time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
Instantaneous measurement of stroke volume at specific time-points during HUTT examination
Peripheral Resistance [Dyn·s/cm5] at Specific Time-points During Head-up Tilt Test (HUTT)
Time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
Instantaneous measurement of peripheral resistance at specific time-points during HUTT examination
Time of Maximum Spontaneous Heart Rate
Time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
Recording of a specific time-point during HUTT examination. This time was collected as hours:minutes:seconds (e.g. 00:35:34).
Time of Pacing Onset
Time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
Recording of a specific time-point during HUTT examination. This time was collected as hours:minutes:seconds (e.g. 00:35:34).
Time of Recovery of Spontaneous Rhythm After Pacing
Time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
Recording of a specific time-point during HUTT examination. This time was collected as hours:minutes:seconds (e.g. 00:35:34).
Time of Syncope
Time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
Recording of a specific time-point during HUTT examination. This time was collected as hours:minutes:seconds (e.g. 00:35:34).
Time of Tilt-down
Time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
Recording of a specific time-point during HUTT examination. This time was collected as hours:minutes:seconds (e.g. 00:35:34).
Duration of the Recovery Phase [Minutes]
Time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
Interval from maximum pacing rate to basic rate or spontaneous rhythm
Slope in Heart Rate [Bpm/Minute] During the Recovery Phase
Time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
Calculation of the rate of change of heart rate from the time of maximum pacing rate to the time of basic rate or spontaneous rhythm recovery
Slope in Systolic Blood Pressure (mmHg Per Minute) During the Recovery Phase
Time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes
Calculation of the rate of change of systolic blood pressure from the time of maximum pacing rate to the time of basic rate or spontaneous rhythm recovery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38340330Russo V, Tomaino M, Parente E, Comune A, Giacopelli D, Napoli P, Gargaro A, Brignole M. Temporal relationship between haemodynamic changes and activation of closed-loop stimulation during a tilt-induced vasovagal syncope. Europace. 2024 Feb 1;26(2):euae045. doi: 10.1093/europace/euae045.
- Individual participant dataSharing planned: Yes. Data will be shared on request to the corresponding author with permission of BIOTRONIK SE \& Co. KG.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Syncope and Syncope, Vasovagal, run by Biotronik SE & Co. KG at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart Rate [Bpm] at Specific Time-points During Head-up Tilt Test (HUTT) Examination (time frame: From the start to the end of the HUTT examination, assessed up to 45 minutes). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06038708, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.