Pacertool Early Feasibility Study - Safety and Performance

Pacertool-Study - Safety and Performance of the Presens-Catheter and the Pacer Software

The study is a non-randomized, two-part, open label, prospective single-site, single arm, safety and performance study. The study is designed to collect acute and long-term clinical data and user reported outcome data from using the PreSens-Catheter and PACER Software during cardiac catheterization and Cardiac Resynchronization Therapy (CRT) device implantation procedures. Subjects with indication for arterial catheterization and CRT will be included.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure With Reduced Ejection Fraction; Dyssynchrony; Medical Device Performance
• Intervention / Treatment: Device: Cardiac catheterization and evoked response to cardiac stimulation

Detailed Description

The study consists of two parts:

1. Initial safety assessment: at least 5 patients undergoing coronary angiography or left heart catheterization and 5 patients undergoing cardiac resynchronization therapy device implantation to demonstrate acute safety and performance of the PreSens-Catheter and the PACER Software for Td measurements.
2. Safety and performance assessment: At least 35 patients with an indication for CRT implantation according to standard of care to demonstrate acute safety and performance of using the PreSens-Catheter and the PACER Software to measure Td and detect Synergy and Dyssynergy from multisite stimulation, and its utility to deliver measurements for the discrimination of two clinical cardiac reverse volumetric remodeling phenotypes based on Synergy and Dyssynergy in the targeted population.

Subjects will be followed for the duration of the procedure up to 24 hours for any serious adverse events, and subjects receiving a CRT device will be followed for 30 days follow-up for procedure or device-related events and for up to 6 months for cardiac volumetric remodeling phenotyping.

Clinical outcomes: Clinical outcome will be measured as Safety for the placement of the PreSens-Catheter, safety for the PreSens-Catheter and PACER Software combined for the measurement of Td and detection of Synergy/ Dyssynergy from stimulation, and diagnostic/ predictive performance of the PreSens-Catheter and PACER Software with the measurement of end-systolic volume at 6-months follow-up.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Hans Henrik Odland, MD, PhD; Phone Number: +4790509944; Email: hho@pacertool.com

Study Locations

• Georgia
  • Tbilisi, Georgia, 0159
    • Tbilisi Heart and Vascular Clinic
    • Contact: Irakli Dvali

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population is adult patients (>18years) with (part I) an indication for left heart catheterization, or (part I and II) a clinical syndrome of heart failure with reduced ejection fraction and normal sinus rhythm with signs of ventricular electrical conduction defects in the heart, who meets standard criteria for implantation of a cardiac resynchronization therapy device.

Description

Inclusion Criteria:

Part I:

• Subject has an indication for coronary angiography or left heart catheterization or cardiac resynchronization therapy.
• QRS duration between 90-150ms.
• Subject is ≥ 18 years old.
• Willingness, ability, and commitment to participate in baseline and follow-up evaluations for the full duration of the clinical study.
• Willing and able to give informed consent.

Part II:

• Subject in sinus rhythm with an indication for implantation of a Cardiac Resynchronization Device (Appendix I)
• NYHA Class II-IV (Ambulatory IV)
• EF<35%
• QRS duration >120ms.
• Subject is ≥ 18 years old.
• Willingness, ability, and commitment to participate in baseline and follow-up evaluations for the full duration of the clinical study.
• Willing and able to give informed consent.

Exclusion Criteria:¨

• Subject has unstable angina/ acute coronary ischemia/ infarction
• Previous myocardial infraction (<6 months)
• History of blood clothing or bleeding disease
• Prior history of documented cerebral infarction, TIA or systemic embolism (excluding a postoperative DVT)
• Subject has an arterial unstable aneurysm
• Subject has severe peripheral vascular disease
• Subject has an artificial aortic or mitral valve replacement
• Subject has severe aortic valve disease
• Subject has a clinically significant infection (bacteriemia or sepsis)
• Subject has contraindications to anticoagulation
• Patients with a serious allergy to drugs necessary for the procedure such as anticoagulants and protamine
• Subject has left atrial/ ventricular thrombus
• Patients with severe vascular obstructions in the desired/ presumed insertion path of the catheter
• Significant or symptomatic hypotension
• NYHA class IV (hospitalized), severe circulation instability or shock
• Ongoing/ persistent atrial arrythmias
• History of Rheumatic fever
• Subject has sensitivity to contrast media
• Contraindications to CT or fluoroscopy
• Distorted cardiac anatomy due to congenital heart disease
• Pregnant or possibly pregnant
• Not eligible for thoracotomy procedures
• Life expectancy <1 years
• Any other condition that, in the judgement of the investigator, makes the subject a poor candidate for this procedure, the study or compliance with the protocol (includes addictive disease, extensive travel away from the research center)
• Clinically significant psychological condition that in the investigator's opinion would prohibit the subject's ability to meet the protocol requirements
• Current enrollment in any other study protocol where testing or results from that study may interfere with the procedure or outcome measurements of this study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; Patients with an indication for left heart catheterization or cardiac resynchornization therapy	Device: Cardiac catheterization and evoked response to cardiac stimulation; Cardiac catheterization with a combined elecrtophysiology and pressure sensing catheter to perform multisite stimulation and measure the evoked pressure response in a connected software.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety Outcome (PreSens-Catheter):	The primary safety outcome is the incidence of procedure or device-related Serious Adverse Events (SAEs and SADEs) on the day of the procedure	24 hours
Primary Safety Outcome Measures (PreSens-Catheter and PACER Software):	The primary safety outcome of the PreSens-Catheter and PACER Software is the incidence of false positive readings of Synergy resulting from multisite stimulation from PreSens-Catheter in patients with narrow QRS and false negative readings (Dyssynergy) compared to the resulting reading from pacing with the CRT device.	4 hours
Primary Performance Outcome Measures (PreSens-Catheter and PACER Software):	Detection of Synergy and Dyssynergy to phenotype patients for the prediction of reverse volumetric remodeling response after 6 months of Cardiac Resynchronization Therapy. Outcome is based on the change in End-Systolic Volume (ESV) from baseline to 6 months follow-up in the respective phenotypes. The study is powered to detect a ΔESV of 30% points difference between the Synergy and Dyssynergy characterized patients after 6 months of Cardiac Resynchronization Therapy.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Outcome Measures (PreSens-Catheter):	Percentage of subjects experiencing a composite safety event. The composite safety outcome (CSO) defined as the incidence of events which are device- or procedure-related	30 days
Performance Outcome Measures (PreSens-Catheter)	a) The proportion of subjects that achieve Acute Procedural Success (APS) defined as the correct insertion and placement of the PreSens-Catheter within the heart with confirmed readings/ recordings from the catheter and imaged with fluoroscopy in two planes, in at least one of the defined positions depending on available access sheets (on an intention-to-treat basis). b) The proportion of subjects that had the PreSens-Catheter placed in the left heart with the intention to place the catheter with the distal electrodes in three different positions (anterior, lateral, posterior); number of positions achieved in each patient. c) Product performance evaluated on a 5-point semi-quantitative scale ("strongly disagree" to "strongly agree") [Time Frame: During Procedure]. d) Acute product performance will be quantitatively and qualitatively evaluated during the procedure.	4 hours
Performance Outcome Measures (PreSens-Catheter and PACER Software):	The proportion of subjects that achieve Acute Procedural Success (APS) defined as successful placement of the PreSens-Catheter in the heart and measurement of Td (time to peak exponential pressure rise (dP/dt)) with the PACER Software; with stimulation from the PreSens-Catheter and from the CRT (with the rate of agreement) with the PreSens-Catheter placed in at least two out of three defined positions. (CRT recipients only).	4 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
iv) Exploratory Performance Outcome Measures (PreSens-Catheter and PACER Software):	(a) Percentage of subjects experiencing (from each position in the left heart): (i) Demonstration of prolongation of Td with pacing off a proximal electrode (ii) Demonstration of prolongation of Td with pacing off a distal electrode (iii) Demonstration of shortening of Td (Synergy) with pacing from electrodes from both electrode groups (distal and proximal) compared to the shortest Td with pacing from either distal or proximal electrode. (iv) Demonstration of shortening of Td (Synergy) with pacing from electrodes from both electrode groups (distal and proximal) compared to baseline Td in patients with QRS duration above 130ms and below or equal to 130ms. (v) Demonstration of prolongation of Td (Dyssynergy) with biventricular pacing (negative responder, true negative result) compared to baseline Td in patients with QRS duration above 130ms and ≤130ms. (vi) Demonstration of a short Td (≤120ms) at baseline in patients with a QRS duration ≤130ms and long Td (>120ms) at baseline in patient	4 hours

Collaborators and Investigators

• Sponsor: Pacertool AS
• Investigators: Principal Investigator: Tamaz Shaburishvili, MD, Tbilisi Heart and Vascular Clinic

Publications and helpful links

General Publications

• Odland HH, Holm T, Cornelussen R, Kongsgard E. Determinants of the time-to-peak left ventricular dP/dt (Td) and QRS duration with different fusion strategies in cardiac resynchronization therapy. Front Cardiovasc Med. 2022 Sep 15;9:979581. doi: 10.3389/fcvm.2022.979581. eCollection 2022.
• Odland HH, Villegas-Martinez M, Ross S, Holm T, Cornelussen R, Remme EW, Kongsgard E. Shortening of time-to-peak left ventricular pressure rise (Td) in cardiac resynchronization therapy. ESC Heart Fail. 2021 Dec;8(6):5222-5236. doi: 10.1002/ehf2.13601. Epub 2021 Sep 12.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 26, 2023

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Early feasibility observational study
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: PaCRTool-Study 012023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No