BIO|STREAM.CSP CLS

May 29, 2026 updated by: Biotronik SE & Co. KG

Observation of Clinical Routine Care for Patients Implanted With BIOTRONIK Devices Used for Conduction System Pacing (CSP) With Focus on Closed Loop Stimulation (CLS)

This clinical study is a prospective, observational submodule of the BIO|STREAM.CSP registry designed to evaluate clinical outcomes in patients receiving BIOTRONIK dual-chamber pacemakers that combine conduction system pacing-specifically left bundle branch area pacing (LBBAP)-with Closed Loop Stimulation (CLS). The purpose of the study is to better understand how this combined pacing strategy performs in routine clinical practice and whether it may help reduce the occurrence of atrial fibrillation in patients with sinus node dysfunction (SND) and concomitant atrioventricular (AV) conduction disorders.

The primary question the study seeks to answer is what the incidence of device-detected atrial fibrillation (DDAF) is over a 24-month follow-up period in patients treated with LBBAP and active CLS. Additionally, the study explores how CLS dynamically modulates pacing rates when the ventricular lead is positioned within the conduction system, and whether this physiological pacing approach may mitigate the negative effects associated with conventional right ventricular pacing.

Overall, this study aims to generate real-world evidence to support optimization of pacemaker programming and to inform clinical decision-making regarding the use of CLS in combination with conduction system pacing, with the goal of improving patient outcomes and reducing atrial arrhythmia burden.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study, BIO|STREAM.CSP CLS, is a prospective, observational submodule of the ongoing BIO|STREAM.CSP registry. It is designed to collect real-world clinical data from patients who receive BIOTRONIK dual-chamber pacemakers using conduction system pacing (CSP), with a specific focus on the combination of left bundle branch area pacing (LBBAP) and Closed Loop Stimulation (CLS).

Permanent cardiac pacing is a standard therapy for patients with sinus node dysfunction (SND), a condition in which the heart's natural pacemaker does not function properly. A considerable proportion of these patients also have atrioventricular (AV) conduction disorders, which impair the electrical connection between the atria and ventricles. In such cases, dual-chamber pacemakers are typically implanted to maintain appropriate heart rhythm and coordination.

Traditional right ventricular (RV) pacing, while effective in maintaining heart rate, has been associated with non-physiological activation of the heart and may contribute to an increased risk of atrial fibrillation (AF), especially when pacing burden is high. Device-detected atrial fibrillation (DDAF) is a clinically relevant outcome, as it is associated with increased risk of stroke, heart failure, and other cardiovascular complications.

Closed Loop Stimulation (CLS) is an advanced pacemaker feature designed to provide more physiological heart rate adaptation by continuously monitoring cardiac contractility and adjusting the pacing rate accordingly. In previous studies, including the B3 trial, CLS demonstrated a reduction in DDAF incidence in patients with SND. However, this benefit was not observed in patients with AV block, likely due to the adverse effects of frequent RV pacing.

Conduction system pacing, and in particular left bundle branch area pacing (LBBAP), is an emerging pacing strategy that stimulates the heart's intrinsic conduction pathways, resulting in a more physiological and synchronized ventricular activation. This approach has the potential to reduce the negative effects associated with RV pacing.

The BIO|STREAM.CSP CLS submodule aims to investigate whether the combination of LBBAP and CLS can reduce the incidence of DDAF in patients with both SND and AV conduction disorders in routine clinical practice. The study will follow approximately 150 patients over a 24-month period after pacemaker implantation. Patients included are those enrolled in the BIO|STREAM.CSP registry who receive a de novo dual-chamber pacemaker with activated CLS and LBBAP, and who have no prior history of atrial fibrillation.

The primary objective of this exploratory submodule is to assess the incidence and timing of DDAF episodes following activation of CLS, using device-based diagnostics over the follow-up period. The study will evaluate multiple thresholds of AF episode duration (e.g., ≥6 minutes, ≥6 hours, ≥24 hours, and ≥7 days), as well as the time to first occurrence and overall AF burden. Secondary analyses will explore how CLS modulates heart rate in patients with conduction system pacing, including the distribution of paced and sensed heart rates over time.

As an observational study without a control group, BIO|STREAM.CSP CLS is intended to generate hypothesis-generating, real-world evidence rather than to test a predefined hypothesis. The findings are expected to provide insights into the clinical performance of CLS in combination with LBBAP and to support optimization of device programming strategies.

Overall, this study seeks to improve understanding of how advanced pacing technologies can be used together to deliver more physiological cardiac pacing, with the goal of reducing atrial arrhythmias and improving long-term outcomes in patients requiring permanent pacemakers.

Study Type

Observational

Enrollment (Estimated)

150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Czechia
      • Ústí nad Labem, Czechia
        • Not yet recruiting
        • Masarykova Nemocnice V Usti Nad Labem
        • Contact:
  • Hungary
  • Italy
      • Brindisi, Italy
      • Milan, Italy
      • Novara, Italy
        • Recruiting
        • A.O.U. Maggiore della Carita di Novara
        • Contact:
      • Piove di Sacco, Italy
      • Roma, Italy
      • Taranto, Italy
        • Not yet recruiting
        • SS Annunziata Taranto
        • Contact:
  • Portugal
      • Coimbra, Portugal
        • Not yet recruiting
        • Unidade local de Saúde de Coimbra, EPE - Centro Hospitalar Universitario de Coimbra
        • Contact:
        • Contact:
          • João Ferreira
  • Spain
      • Madrid, Spain
        • Not yet recruiting
        • Hospital Universitario 12 de Octubre
        • Contact:
      • Valencia, Spain
        • Not yet recruiting
        • Hospital Universitario La Fe
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with an indication for de novo dual-chamber pacing due to SND with evidence of AV conduction disorders, enrolled in the BIO|STREAM.CSP registry.

Description

Inclusion Criteria:

  • Enrolled in the BIO|STREAM.CSP registry
  • Standard indication for dual-chamber pacing due to any form of sinus node disease according to guidelines
  • DDD-CLS pacing mode activated
  • Either ≥ II degree AV block, or native PR interval ≥ 200 ms at baseline ECG with expected RVP ≥ 20%

Exclusion Criteria:

  • Implantation dates back more than 90 days
  • History of clinical AF
  • Patients intended to receive, or already received a pacing lead for traditional RV pacing, His bundle pacing or right bundle branch pacing
  • Upgrade from previous pacemaker system
  • Patients transitioning from the BIO|MASTER.CSP study
  • DDAF episodes present in the device memory at the time of registration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DDAF incidence
Time Frame: From CLS activation to 24 months after implantation
Time from CLS activation to the first device-detected atrial fibrillation (DDAF) episode of different duration cutoffs (6 minutes, 6 hours, 24 hours, 7 days) through 24 months of follow-up after implantation
From CLS activation to 24 months after implantation
DDAF burden
Time Frame: From CLS activation to 24 months after implantation
The time from CLS activation to the first day with a DDAF burden ≥1% (≈15 minutes) determined within a follow-up period of 24 months after implantation
From CLS activation to 24 months after implantation
Heart Rate histograms
Time Frame: At 1 year and 2 years after implantation
Heart Rate histograms of sensed and paced beats [% time] at 1-year and 2-year follow-ups
At 1 year and 2 years after implantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biotronik SE & Co. KG

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 29, 2026

Primary Completion (Estimated)

May 29, 2028

Study Completion (Estimated)

May 29, 2030

Study Registration Dates

First Submitted

May 20, 2026

First Submitted That Met QC Criteria

May 20, 2026

First Posted (Actual)

May 27, 2026

Study Record Updates

Last Update Posted (Actual)

June 2, 2026

Last Update Submitted That Met QC Criteria

May 29, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BA121

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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