## Protocol Section
### Identification Module
**NCT ID:** NCT05541679

**Brief Title:** Comparison of Left Bundle Branch Area Versus Right Ventricular Septal Pacing in Patients With High-degree Conduction Disease After Transcatheter Aortic Valve Replacement (Left Bundle BRAVE)

**Official Title:** Comparison of Left Bundle Branch Area Versus Right Ventricular Septal Pacing in Patients With High-degree Conduction Disease After Transcatheter Aortic Valve Replacement

#### Organization Study ID Info
**ID:** E-22-5212
#### Organization
**Class:** OTHER
**Full Name:** Main Line Health
### Status Module
#### Completion Date
**Date:** 2025-12-31

**Type:** ESTIMATED

#### Last Update Post Date
**Date:** 2024-01-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-01-29

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-12-28

**Type:** ACTUAL

**Status Verified Date:** 2024-01

#### Study First Post Date
**Date:** 2022-09-15
**Type:** ACTUAL
**Study First Submit Date:** 2022-09-13
**Study First Submit QC Date:** 2022-09-13
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Medtronic

**Class:** OTHER

**Name:** Sharpe-Strumia Research Foundation

#### Lead Sponsor

**Class:** OTHER

**Name:** Main Line Health

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** True

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The purpose of the study is to investigate the superiority of chronic left bundle branch area pacing compared to traditional right ventricular (RV) septal pacing in patients with high-grade conduction disease after transcatheter aortic valve replacement (TAVR). In this investigator initiated, multicenter, prospective, double-blinded, crossover study, chronic left bundle branch area pacing will be compared to chronic right ventricular septal pacing using echocardiographic measures of left ventricular systolic function in patients with a high cumulative ventricular pacing burden after TAVR.

### Conditions Module

**Conditions:**

- Complete Heart Block

- High Degree Second Degree Atrioventricular Block

- Pacemaker-Induced Cardiomyopathy

- Aortic Valve Stenosis

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 46

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Device: Right ventricular septal pacing followed by left bundle branch area pacing

**Label:** Group A

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Device: Left bundle branch area pacing followed by right ventricular septal pacing

**Label:** Group B

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Group A

**Description:** All patients will undergo implantation of right ventricular septal lead, left bundle branch area lead, and atrial lead in the absence of permanent atrial fibrillation with a CRT-pacing generator. Patients will be randomized to pacing protocols based on group assignment and crossover during the study.

**Name:** Right ventricular septal pacing followed by left bundle branch area pacing

**Type:** DEVICE

#### Intervention 2

**Arm Group Labels:**

- Group B

**Description:** All patients will undergo implantation of right ventricular septal lead, left bundle branch area lead, and atrial lead in the absence of permanent atrial fibrillation with a CRT-pacing generator. Patients will be randomized to pacing protocols based on group assignment and crossover during the study.

**Name:** Left bundle branch area pacing followed by right ventricular septal pacing

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** Primary efficacy outcome

**Measure:** Change in global longitudinal strain (GLS%)

**Time Frame:** 9 months

**Description:** Primary efficacy outcome

**Measure:** Change in left ventricular ejection fraction (LVEF%)

**Time Frame:** 9 months

**Description:** Primary safety endpoint

**Measure:** Composite of left bundle branch area pacing lead septal myocardial or coronary artery perforation, lead dislodgment, and repeat procedures related to left bundle branch area lead implantation

**Time Frame:** 18 months

#### Secondary Outcomes

**Measure:** Adverse events related to device function

**Time Frame:** 18 months

**Measure:** Quality of life measured using the Minnesota Living with Heart Failure questionnaire (MLHQ)

**Time Frame:** 9 months

**Measure:** Functional capacity measured using the New York Heart Association functional classification (NYHA)

**Time Frame:** 9 months

**Measure:** Six minute walk test score

**Time Frame:** 9 months

**Measure:** Hospitalizations for heart failure

**Time Frame:** 18 months

**Measure:** Mortality

**Time Frame:** 18 months

**Measure:** Right ventricular global longitudinal strain (RVGLS%)

**Time Frame:** 9 months

**Measure:** Left ventricular mechanical systolic dyssynchrony indexed to heart rate (SDI)

**Time Frame:** 9 months

**Measure:** Interventricular mechanical delay (IVMD)

**Time Frame:** 9 months

**Measure:** Left ventricular end-systolic volume

**Time Frame:** 9 months

**Measure:** Left ventricular stroke volume

**Time Frame:** 9 months

**Measure:** Severity of tricuspid regurgitation

**Time Frame:** 18 months

**Measure:** Severity of mitral regurgitation

**Time Frame:** 18 months

**Measure:** Left bundle branch area pacing lead pacing threshold

**Time Frame:** 18 months

**Measure:** Left bundle branch area pacing lead sensed R wave amplitude

**Time Frame:** 18 months

**Measure:** Left bundle branch area pacing lead impedence

**Time Frame:** 18 months

**Measure:** Brain natriuretic peptide or N-terminal pro-brain natriuretic peptide concentration

**Time Frame:** 9 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Subject has at least one of these conduction disturbances:

  1. Symptomatic (or hemodynamically significant) bradycardia or symptomatic persistent atrioventricular block including first-degree and Mobitz I (Wenckebach) or Mobitz type II atrioventricular bock
  2. High-grade atrioventricular block
  3. Third-degree atrioventricular block
* Subject has undergone TAVR (any valve system) in the last four weeks
* Subject is receiving a first-time pacemaker implant
* Subject's most recent documented ejection fraction (by any method) within the past 90 days prior to study enrollment is \> 50% (≥45% if visually estimated at the time of enrollment)
* Subject is a male or female at least 18 years old at the time of consent
* Subject is able to receive a left sided pectoral implant

Exclusion Criteria:

* Subject has ever had a previous or has an existing implantable pulse generator (IPG), implantable cardiac defibrillator (ICD) or biventricular (BiV) implant
* Subject has more than mild para-valvular regurgitation following TAVR implantation.
* Subject has LVEF \< 45% if visually estimated at the time of enrollment
* Subject is indicated for a biventricular pacing device (CRT-P or CRT-D).
* Subject is enrolled in a concurrent study that may confound the results of this study
* Subject has a mechanical heart valve
* Subject is pregnant, or of childbearing potential and not on a reliable form of birth control
* Subject status post heart transplant
* Subject life expectancy less than 2 years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** keramatia@mlhs.org

**Name:** Ali Keramati, MD

**Phone:** 484-476-1000

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Overland Park

**Contacts:**

***Contact 1:***

- **Name:** Krishna Pothineni, MD

- **Role:** CONTACT

**Country:** United States

**Facility:** Kansas City Heart Rhythm Institute

**State:** Kansas

**Status:** RECRUITING

**Zip:** 66211

**Location 2:**

**City:** Ridgewood

**Contacts:**

***Contact 1:***

- **Name:** Mohammadali Habibi, MD

- **Role:** CONTACT

**Country:** United States

**Facility:** Valley Health System

**State:** New Jersey

**Status:** RECRUITING

**Zip:** 07450

**Location 3:**

**City:** Philadelphia

**Contacts:**

***Contact 1:***

- **Name:** Robert Schaller, DO

- **Role:** CONTACT

**Country:** United States

**Facility:** Hospital of the University of Pennsylvania

**State:** Pennsylvania

**Status:** RECRUITING

**Zip:** 19104

**Location 4:**

**City:** Wynnewood

**Contacts:**

***Contact 1:***

- **Name:** Ali Keramati, MD

- **Role:** CONTACT

***Contact 2:***

- **Name:** Steven Liskov, MD

- **Role:** SUB_INVESTIGATOR

**Country:** United States

**Facility:** Lankenau Medical Center

**State:** Pennsylvania

**Status:** RECRUITING

**Zip:** 19096

#### Overall Officials

**Official 1:**

**Affiliation:** Lankenau Heart Institute

**Name:** Ali Keramati, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006331

- Term: Heart Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000082862

- Term: Aortic Valve Disease

- ID: D000006349

- Term: Heart Valve Diseases

- ID: D000014694

- Term: Ventricular Outflow Obstruction

- ID: D000001145

- Term: Arrhythmias, Cardiac

- ID: D000075224

- Term: Cardiac Conduction System Disease

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M12154

- Name: Cardiomyopathies

- Relevance: HIGH

- As Found: Cardiomyopathy

- ID: M6475

- Name: Constriction, Pathologic

- Relevance: LOW

- As Found: Unknown

- ID: M4340

- Name: Aortic Valve Stenosis

- Relevance: HIGH

- As Found: Aortic Valve Stenosis

- ID: M9415

- Name: Heart Block

- Relevance: HIGH

- As Found: Heart Block

- ID: M27765

- Name: Atrioventricular Block

- Relevance: HIGH

- As Found: Atrioventricular Block

- ID: M9419

- Name: Heart Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2379

- Name: Aortic Valve Disease

- Relevance: LOW

- As Found: Unknown

- ID: M9437

- Name: Heart Valve Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17440

- Name: Ventricular Outflow Obstruction

- Relevance: LOW

- As Found: Unknown

- ID: M4453

- Name: Arrhythmias, Cardiac

- Relevance: LOW

- As Found: Unknown

- ID: M1472

- Name: Cardiac Conduction System Disease

- Relevance: LOW

- As Found: Unknown

- ID: T449

- Name: Aortic Valve Stenosis

- Relevance: HIGH

- As Found: Aortic Valve Stenosis

### Condition Browse Module - Meshes

- ID: D000009202

- Term: Cardiomyopathies

- ID: D000001024

- Term: Aortic Valve Stenosis

- ID: D000054537

- Term: Atrioventricular Block

- ID: D000006327

- Term: Heart Block

### Misc Info Module

- Version Holder: 2024-05-24
