PV Loops With CNT in Multiple Pacing Sites (CS-07)
Primary Purpose
Bradycardia, A-V Block
Status
Not yet recruiting
Phase
Not Applicable
Locations
Poland
Study Type
Interventional
Intervention
Moderato
Sponsored by
About this trial
This is an interventional basic science trial for Bradycardia
Eligibility Criteria
Inclusion Criteria:
- Subject is ≥ 18 years of age.
- Subject is indicated for an implant or a replacement with a planned upgrade of a device capable of pacing (pacemaker, ICD, CRT-P, CRT-D).
- Subject is willing and able to comply with the study procedures.
Exclusion Criteria:
- Subject is dependent on 100% ventricular pacing.
- Subject has symptoms of heart failure, NYHA Class III or greater
- Subject has an ejection fraction of 25% or less
- Subject's systolic blood pressure is less than 100 mmHg on the day of implant
- Subject has decompensated heart failure
- Subject has significant (>2+) valvular regurgitation or any valvular stenosis.
- Subject has permanent atrial fibrillation
- Subject has atrial fibrillation on the day of the study.
- Subject has hypertrophic cardiomyopathy, restrictive cardiomyopathy, or interventricular septal thickness ≥15 mm
- Subject is on dialysis
- Subject has a history of prior neurological events (stroke or TIA) within the past year or a neurological event (stroke) at any prior time that has resulted in residual neurologic deficit.
- Subject has a history of autonomic dysfunction
- Patient cannot receive heparin for any reason (such as a history of Heparin induced thrombocytopenia (HIT))
- Women who are pregnant or breast-feeding
- Subject cannot or is unwilling to provide informed consent.
Sites / Locations
- University Hospital, Jagiellonian University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental group
Arm Description
Eligible subjects instrumented for CNT testing
Outcomes
Primary Outcome Measures
Average changes in Systolic Blood Pressure Change
When compared to standard pacing, CNT elicits a reduction in Systolic Blood Pressure (mmHg)
Secondary Outcome Measures
Average Cardiac Volumes (End Diastolic and End Systolic volumes, stroke volumes)
When compared to standard pacing, CNT varies cardiac volumes (ml)
Average Ejection Fraction (the percent of blood volume ejected per beat)
When compared to standard pacing, CNT varies Ejection Fraction (EF, %)
Average Cardiac Pressures (End Systolic and Diastolic Pressures)
When compared to standard pacing, CNT varies cardiac pressures (mmHg)
Average cardiac contractility
When compared to standard pacing, CNT varies cardiac contractility (mmHg/sec)
Average Systemic Vascular Resistance
When compared to standard pacing, CNT Systemic Resistance (ml/mmHg/sec)
Full Information
NCT ID
NCT05345925
First Posted
April 8, 2022
Last Updated
April 26, 2023
Sponsor
BackBeat Medical Inc
Collaborators
CD Leycom
1. Study Identification
Unique Protocol Identification Number
NCT05345925
Brief Title
PV Loops With CNT in Multiple Pacing Sites
Acronym
CS-07
Official Title
Pressure-Volume (PV) Measurements for Evaluating Cardiac Parameters Using BackBeat Medical's Cardiac Neuromodulation Therapy (CNT) Pacing Signals in Different Physiological Pacing Sites: An Acute Study
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 2, 2023 (Anticipated)
Primary Completion Date
July 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BackBeat Medical Inc
Collaborators
CD Leycom
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
In a multicenter non-randomized acute setting, eligible subjects requiring implant or replacement of an IPG (pacemaker, ICD, CRT-P, CRT-D) will be instrumented to study the effect of CNT from different locations in the RV. CNT effects on BP will be evaluated with a PV conductance catheter in the LV, and with optional BP catheters in the aorta and/or RV. CNT will be delivered by externally by the BackBeat Moderato System IPG.
Abbreviations: CNT, Cardiac Neuromodulation Therapy; IPG, Implanted Pulse Generator; ICD, Implanted Cardiac Defribillator; CRT-P or D, Cardiac Resynchronisation Therapy-Pacemaker or Defibrillator; RV, Right Ventricle; LV, Left Ventricle; BP, Blood Pressure
Detailed Description
This will be a multi-center, pilot, open-label, non-randomized acute study. The Moderato System is approved for marketing in Europe (has a CE mark) for standard pacing and the treatment of high blood pressure in patients requiring standard cardiac pacing. The therapy delivered by the Moderato® System is referred to as CNT (Cardiac Neuromodulation Therapy).
This investigation will evaluate the effect of different pacing lead positions on cardiac function and the modulation of the autonomic nervous system using Cardiac Neuromodulation Therapy (CNT) pacing signals. The Study includes both patient who have hypertension and patients that do not have hypertension. Moderato®system is currently not indicated for patients that do not have hypertension.
Subjects indicated for an implant or replacement of a device capable of pacing (pacemaker, ICD, CRT-P, CRT-D) who meet the study inclusion and exclusion criteria may participate in the study and will undergo the following procedure during their device implantation or replacement:
A Right Atrial (RA) lead will be positioned according to standard procedure of the initially planned device implant, or kept in place (in device replacement), or only temporarily introduced and used for the trial procedure. Existing ventricular leads (if any) can be used for the trial procedure, too. The ventricular lead will be temporarily positioned in the different pacing sites according to the following order: RV septal, LBBA, LBB. Pacing and CNT will be performed in each of these sites unless the site is unreachable or pacing is not possible. When trial procedures are finished, the ventricular lead will be positioned according to best practices of the implant or replacement procedure the patient is undergoing. Any lead used temporarily would be removed.
The leads will be connected to a BackBeat Moderato® System IPG, externally to the patient, using a single use, sterile Pacing System Analyzer (PSA) cable provided by the hospital. The Moderato®IPG - which is approved for chronic CNT delivery in hypertensive patients - will function in this trial as a temporary external CNT signal generator for acute application of the therapy; it will not be in direct contact with the subject.
A standard conductance catheter (CD Leycom, The Netherlands) will be introduced through the femoral artery and advanced into the left ventricle to measure cardiac volumes and pressure.
Arterial blood pressure will be measured by introducing a pressure sensor (e.g., Millar catheter) either from another femoral artery sheath or from a radial arterial line.
Right ventricular blood pressure measurements will be taken by introducing a pressure sensor (e.g., Millar catheter) to the right ventricle through an axillary or subclavian sheath.
The Moderato®IPG will be used to generate standard pacing and Cardiac Neuromodulation Therapy (CNT) signals and deliver them to the patient through the cable and leads. A range of CNT signal parameters will be used to assess the effect on sympathetic activity at the different lead positions. Ventricular pressure and volume readings from the conductance catheter, arterial pressure readings and right ventricle pressure readings will be recorded and analyzed to assess the effect of CNT signals on cardiac function, sympathetic activity and blood pressure. The effects of CNT signal over a range of parameter settings will be studied in the different lead positions.
Simultaneous recording of the ventricular and arterial pressures, ventricular volume measurements and ECG signals will be performed in every pacing site during both pacing and CNT using the LEYCOM® Inca (IntraCardiac Analyzer) system, an integrated, stand-alone system for constant monitoring of intra-ventricular pressure and volume (CE marked).
In this study, none of the Moderato® system components will be in contact with the patient. The Moderato® IPG will be used solely as an external CNT signal generator and deliver signals to the patient through the PSA cable and the pacemaker leads.
When CNT signal activation is complete, data recording will be stopped, the conductance catheter will be removed, the cable connecting the IPG to the leads disconnected, and device implantation (or replacement) will proceed normally. Any pacing lead used temporarily would be removed if not required for ongoing patient treatment.
Patients will be considered as having completed the study at the conclusion of the acute procedure unless a safety event is observed during the acute procedure in which case the patients will be followed until the event has been resolved.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bradycardia, A-V Block
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental group
Arm Type
Experimental
Arm Description
Eligible subjects instrumented for CNT testing
Intervention Type
Device
Intervention Name(s)
Moderato
Intervention Description
Several algorithms comprising CNT will be delivered by the Moderato Implantable Pulse Generator. Each application will last approximately 3 min with 2 minutes baseline (regular pacing) between them. Hence, each subject will serve as its own control (during pacing) and test (during CNT application). Furthermore, the average control value for the whole group will be compared with the average test values of CNT algorithms at the different ventricular lead locations for efficacy assessments. Stratification of subjects by initial hemodynamic parameters (such as Ejection Fraction, for example) would be possible depending on the total number of subjects in each group.
Primary Outcome Measure Information:
Title
Average changes in Systolic Blood Pressure Change
Description
When compared to standard pacing, CNT elicits a reduction in Systolic Blood Pressure (mmHg)
Time Frame
through study completion (18 months)
Secondary Outcome Measure Information:
Title
Average Cardiac Volumes (End Diastolic and End Systolic volumes, stroke volumes)
Description
When compared to standard pacing, CNT varies cardiac volumes (ml)
Time Frame
through study completion (18 months)
Title
Average Ejection Fraction (the percent of blood volume ejected per beat)
Description
When compared to standard pacing, CNT varies Ejection Fraction (EF, %)
Time Frame
through study completion (18 months)
Title
Average Cardiac Pressures (End Systolic and Diastolic Pressures)
Description
When compared to standard pacing, CNT varies cardiac pressures (mmHg)
Time Frame
through study completion (18 months)
Title
Average cardiac contractility
Description
When compared to standard pacing, CNT varies cardiac contractility (mmHg/sec)
Time Frame
through study completion (18 months)
Title
Average Systemic Vascular Resistance
Description
When compared to standard pacing, CNT Systemic Resistance (ml/mmHg/sec)
Time Frame
through study completion (18 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject is ≥ 18 years of age.
Subject is indicated for an implant or a replacement with a planned upgrade of a device capable of pacing (pacemaker, ICD, CRT-P, CRT-D).
Subject is willing and able to comply with the study procedures.
Exclusion Criteria:
Subject is dependent on 100% ventricular pacing.
Subject has symptoms of heart failure, NYHA Class III or greater
Subject has an ejection fraction of 25% or less
Subject's systolic blood pressure is less than 100 mmHg on the day of implant
Subject has decompensated heart failure
Subject has significant (>2+) valvular regurgitation or any valvular stenosis.
Subject has permanent atrial fibrillation
Subject has atrial fibrillation on the day of the study.
Subject has hypertrophic cardiomyopathy, restrictive cardiomyopathy, or interventricular septal thickness ≥15 mm
Subject is on dialysis
Subject has a history of prior neurological events (stroke or TIA) within the past year or a neurological event (stroke) at any prior time that has resulted in residual neurologic deficit.
Subject has a history of autonomic dysfunction
Patient cannot receive heparin for any reason (such as a history of Heparin induced thrombocytopenia (HIT))
Women who are pregnant or breast-feeding
Subject cannot or is unwilling to provide informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yuval Mika, Ph.D.
Phone
+18569123155
Email
ymika@orchestrabiomed.com
First Name & Middle Initial & Last Name or Official Title & Degree
Norbert Rosenthal, B.Sc.
Phone
+491792482543
Email
nrosenthal@orchestrabiomed.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marek Jastrzębski,, MD, PhD
Organizational Affiliation
Jagiellonian University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital, Jagiellonian University
City
Kraków
ZIP/Postal Code
30-688
Country
Poland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marek Jastrzębski,, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
17853871
Citation
Klotz S, Dickstein ML, Burkhoff D. A computational method of prediction of the end-diastolic pressure-volume relationship by single beat. Nat Protoc. 2007;2(9):2152-8. doi: 10.1038/nprot.2007.270.
Results Reference
background
PubMed Identifier
29275370
Citation
Neuzil P, Merkely B, Erglis A, Marinskis G, de Groot JR, Schmidinger H, Rodriguez Venegas M, Voskuil M, Sturmberger T, Petru J, Jongejan N, Aichinger J, Kamzola G, Aidietis A, Geller L, Mraz T, Osztheimer I, Mika Y, Evans S, Burkhoff D, Kuck KH; BackBeat Study Investigators. Pacemaker-Mediated Programmable Hypertension Control Therapy. J Am Heart Assoc. 2017 Dec 23;6(12):e006974. doi: 10.1161/JAHA.117.006974.
Results Reference
result
PubMed Identifier
29628351
Citation
Yang B, Wang Y, Zhang F, Ju W, Chen H, Mika Y, Aviv R, Evans SJ, Burkhoff D, Wang J, Chen M. Rationale and evidence for the development of a durable device-based cardiac neuromodulation therapy for hypertension. J Am Soc Hypertens. 2018 May;12(5):381-391. doi: 10.1016/j.jash.2018.03.004. Epub 2018 Mar 21.
Results Reference
result
PubMed Identifier
34387126
Citation
Kalarus Z, Merkely B, Neuzil P, Grabowski M, Mitkowski P, Marinskis G, Erglis A, Kazmierczak J, Sturmberger T, Sokal A, Pluta S, Geller L, Osztheimer I, Malek F, Kolodzinska A, Mika Y, Evans SJ, Hastings HM, Burkhoff D, Kuck KH. Pacemaker-Based Cardiac Neuromodulation Therapy in Patients With Hypertension: A Pilot Study. J Am Heart Assoc. 2021 Aug 17;10(16):e020492. doi: 10.1161/JAHA.120.020492. Epub 2021 Aug 13.
Results Reference
result
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PV Loops With CNT in Multiple Pacing Sites
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