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Direct HIS/LBB Pacing as an Alternative to Biventricular Pacing in Patients With HFrEF and a Typical LBBB. (HIS-alt_2)

Primary Purpose

Heart Failure, Left Bundle-Branch Block

Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
HIS/LBB pacing
LV pacing
Sponsored by
Rigshospitalet, Denmark
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring left bundle branch block, HIS-pacing, LBB-pacing, left bundle branch pacing

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients over 18 years of age, ischemic or non-ischemic cardiomyopathy with LVEF ≤ 35% assessed by echocardiography, NYHA class II-IV heart failure symptoms despite optimal medical treatment and

    • Either planned new implantation of a biventricular pacing system (CRT-P or CRT-D), where the ECG is with sinus rhythm and a typical left bundle branch block (see definition below)
    • Or planned upgrade of an existing pacemaker or ICD to a biventricular pacing system (CRT-P or CRT-D), where the ECG is with sinus rhythm and a typical left bundle branch block or there has been> 90% right ventricular pacing from an existing pacemaker for at least 2 months prior to enrollment
  • Signed informed consent

Typical left bundle branch block:

QRS width > 130 msec for women and > 140 msec for men QS or rS pattern in leads V1 and V2, and mid-QRS plateau phase with or without extras in at least 2 of leads V1, V2, V5, V6, I, and aVL

Exclusion Criteria:

  • Existing biventricular pacing system
  • Permanent atrial fibrillation
  • Severe renal failure with eGFR < 30 ml/min
  • AMI or CABG within the last three months
  • The patient does not want to participate

Sites / Locations

  • RigshospitaletRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

HIS/LBB pacing

LV pacing

Arm Description

In this arm a right ventricular (RV) lead or implantable cardioverter defibrillator (ICD) lead is placed first and then implantation of a HIS-pacing lead is attempted. If it is not possible to find and pace HIS, to correct the LBBB or the threshold for correcting the LBBB is > 2.5 V at 1 ms, implantation of a LBB-pacing lead is attempted instead. If that is not possible either, a left ventricular (LV) lead is implanted.

In this arm an RV-lead or ICD-lead is placed first and then implantation of a LV-pacing lead is attempted. If this is not possible due to anatomical difficulties (no coronary sinus (CS) access, no available branches other than v cordis anterior or v cordis media) or electrical difficulties (no capture below 4 V at 1.0 msec or phrenic nerve stimulation < 2x pacing threshold), implantation of a HIS-pacing lead is attempted instead. If that is not possible or the threshold for correcting the LBBB is > 2.5 V at 1 ms, implantation of a LBB-pacing lead is attempted instead.

Outcomes

Primary Outcome Measures

Change in Left ventricular end-systolic volume
Echocardiographic response after 6 months defined as decrease in left ventricular systolic volume of ≥ 15% of baseline
Success rate of implanting a HIS-bundle lead with capture of the left bundle branch or a LBB-lead with narrowing of QRS
The success rate of implanting a pacing lead to the HIS-bundle with capture of the left bundle at a threshold < 2.5 V at 1 ms or implantation of a LBB lead with narrowing of the QRS duration and maintaining this effect at 6 month follow-up

Secondary Outcome Measures

Change in LVEF and left ventricular chamber dimensions
Echocardiographic response assessed by chamber dimensions and LVEF on a continuous scale
Change in 6-min hall-walk test
Functional response after 6 months defined as an increase in 6-min walking distance of ≥ 20% of the initial value
Change in NYHA class
Symptomatic response after 6 months defined as a fall in NYHA class of ≥ 1
Change in Minnesota Living with Heart Failure score
Change in well-being after 6 months defined as a decrease in Minnesota Living With Heart Failure score of ≥ 15% of baseline
Shortening of QRS duration
Shortening the duration of the QRS complex defined as the widest paced QRS complex rated at 12-lead ECG after 6 months
Change in NT-pro BNP value
Change in NT-pro BNP value
Complications
Device-related complications (periprocedural: electrode reoperation, pneumothorax, hemothorax, pericardial bleeding/tamponade and later (after 30 days post implantation): LV/HIS electrode reoperation, change of device due to battery depletion and infection requiring extraction).

Full Information

First Posted
May 26, 2020
Last Updated
October 16, 2023
Sponsor
Rigshospitalet, Denmark
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1. Study Identification

Unique Protocol Identification Number
NCT04409119
Brief Title
Direct HIS/LBB Pacing as an Alternative to Biventricular Pacing in Patients With HFrEF and a Typical LBBB.
Acronym
HIS-alt_2
Official Title
Direct HIS/LBB Pacing as an Alternative to Biventricular Pacing in Patients With Symptomatic Heart Failure Despite Optimal Medical Treatment and an ECG With a Typical Left Bundle Branch Block Pattern.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2020 (Actual)
Primary Completion Date
July 1, 2024 (Anticipated)
Study Completion Date
December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rigshospitalet, Denmark

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The study will investigate the feasibility of using direct HIS pacing or left bundle branch pacing (LBB pacing) as an alternative to biventricular pacing in patients with symptomatic heart failure and an ECG with a typical left bundle branch block pattern.
Detailed Description
Biventricular pacing has for more than a decade been standard of care for patients with HFrEF, LVEF < 35%, NYHA II-IV despite optimal medical treatment and an ECG with left bundle branch block (LBBB). However, it is not always ideal because of several drawbacks such as phrenic nerve capture, inability to reach late activated areas and many more. Direct HIS pacing can in many cases capture the left bundle and provide normal electrical activation of the left ventricle but sometimes with high pacing thresholds. Recently direct left bundle branch pacing has shown promise with synchronous activation of the left ventricle at low pacing thresholds. In the present study we randomize 125 patients in one center to either conventional CRT (45 patients) or HIS/LBB pacing (80 patients). In the HIS/LBB arm, direct HIS-pacing is attempted first but if its not possible or the pacing threshold for capturing the left bundle branch is > 2.5 V at 1 ms we switch to placing a LBB-lead. Power calculation for non-inferiority: With the 50 patients in the first His Alternative study (25 Biv-CRT og 25 His-CRT) we observed a fall in systolic volumes of 34% and 46% with a standard deviation of 13-16%. Using these numbers it would take at least 108 patients to be 90% sure that the lower limit of a one-sided 97.5% confidence interval (equal to a 95% two-sided confidence interval) would be over the non-inferiority limit of -10%.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Left Bundle-Branch Block
Keywords
left bundle branch block, HIS-pacing, LBB-pacing, left bundle branch pacing

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Masking Description
The patient and the staff performing and evaluating echocardiography and hall-walk tests are blinded to the treatment arm
Allocation
Randomized
Enrollment
125 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HIS/LBB pacing
Arm Type
Experimental
Arm Description
In this arm a right ventricular (RV) lead or implantable cardioverter defibrillator (ICD) lead is placed first and then implantation of a HIS-pacing lead is attempted. If it is not possible to find and pace HIS, to correct the LBBB or the threshold for correcting the LBBB is > 2.5 V at 1 ms, implantation of a LBB-pacing lead is attempted instead. If that is not possible either, a left ventricular (LV) lead is implanted.
Arm Title
LV pacing
Arm Type
Active Comparator
Arm Description
In this arm an RV-lead or ICD-lead is placed first and then implantation of a LV-pacing lead is attempted. If this is not possible due to anatomical difficulties (no coronary sinus (CS) access, no available branches other than v cordis anterior or v cordis media) or electrical difficulties (no capture below 4 V at 1.0 msec or phrenic nerve stimulation < 2x pacing threshold), implantation of a HIS-pacing lead is attempted instead. If that is not possible or the threshold for correcting the LBBB is > 2.5 V at 1 ms, implantation of a LBB-pacing lead is attempted instead.
Intervention Type
Device
Intervention Name(s)
HIS/LBB pacing
Intervention Description
3830 lead to HIS or LBB
Intervention Type
Device
Intervention Name(s)
LV pacing
Intervention Description
LV lead in a CS branch
Primary Outcome Measure Information:
Title
Change in Left ventricular end-systolic volume
Description
Echocardiographic response after 6 months defined as decrease in left ventricular systolic volume of ≥ 15% of baseline
Time Frame
6 months
Title
Success rate of implanting a HIS-bundle lead with capture of the left bundle branch or a LBB-lead with narrowing of QRS
Description
The success rate of implanting a pacing lead to the HIS-bundle with capture of the left bundle at a threshold < 2.5 V at 1 ms or implantation of a LBB lead with narrowing of the QRS duration and maintaining this effect at 6 month follow-up
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Change in LVEF and left ventricular chamber dimensions
Description
Echocardiographic response assessed by chamber dimensions and LVEF on a continuous scale
Time Frame
6 months
Title
Change in 6-min hall-walk test
Description
Functional response after 6 months defined as an increase in 6-min walking distance of ≥ 20% of the initial value
Time Frame
6 months
Title
Change in NYHA class
Description
Symptomatic response after 6 months defined as a fall in NYHA class of ≥ 1
Time Frame
6 months
Title
Change in Minnesota Living with Heart Failure score
Description
Change in well-being after 6 months defined as a decrease in Minnesota Living With Heart Failure score of ≥ 15% of baseline
Time Frame
6 months
Title
Shortening of QRS duration
Description
Shortening the duration of the QRS complex defined as the widest paced QRS complex rated at 12-lead ECG after 6 months
Time Frame
6 months
Title
Change in NT-pro BNP value
Description
Change in NT-pro BNP value
Time Frame
6 months
Title
Complications
Description
Device-related complications (periprocedural: electrode reoperation, pneumothorax, hemothorax, pericardial bleeding/tamponade and later (after 30 days post implantation): LV/HIS electrode reoperation, change of device due to battery depletion and infection requiring extraction).
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients over 18 years of age, ischemic or non-ischemic cardiomyopathy with LVEF ≤ 35% assessed by echocardiography, NYHA class II-IV heart failure symptoms despite optimal medical treatment and Either planned new implantation of a biventricular pacing system (CRT-P or CRT-D), where the ECG is with sinus rhythm and a typical left bundle branch block (see definition below) Or planned upgrade of an existing pacemaker or ICD to a biventricular pacing system (CRT-P or CRT-D), where the ECG is with sinus rhythm and a typical left bundle branch block or there has been> 90% right ventricular pacing from an existing pacemaker for at least 2 months prior to enrollment Signed informed consent Typical left bundle branch block: QRS width > 130 msec for women and > 140 msec for men QS or rS pattern in leads V1 and V2, and mid-QRS plateau phase with or without extras in at least 2 of leads V1, V2, V5, V6, I, and aVL Exclusion Criteria: Existing biventricular pacing system Permanent atrial fibrillation Severe renal failure with eGFR < 30 ml/min AMI or CABG within the last three months The patient does not want to participate
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Berit Th Philbert, MD PhD
Phone
+4535451410
Email
berit.thornvig.philbert@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Niels Risum, MD PhD
Phone
+4535456995
Email
niels.risum.01@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Vinther, MD PhD
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rigshospitalet
City
Copenhagen
State/Province
Hovedstaden
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Vinther, MD PhD
Phone
+4535456994
Email
michael.vinther@regionh.dk
First Name & Middle Initial & Last Name & Degree
Anne-Sofie Ellekilde, RN
Phone
+4535450923
Email
Anne-sofie.ellekilde@regionh.dk

12. IPD Sharing Statement

Learn more about this trial

Direct HIS/LBB Pacing as an Alternative to Biventricular Pacing in Patients With HFrEF and a Typical LBBB.

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