Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a randomized, prospective, single-blinded trial to determine the overall rate of successful His-Purkinje conduction system pacing Optimized Trial of Cardiac Resynchronization Therapy (HOT-CRT) versus biventricular pacing using coronary sinus lead (BVP) to compare acute and mid-term outcomes. Acute outcomes include change in QRS duration pre-and post-pacing (degree of QRS narrowing) and incidence of major periprocedural complications (pericardial tamponade, need for lead revision, etc.). Mid-term outcomes include echocardiographic response at 6 months along with a composite clinical outcome of heart failure hospitalization, ventricular arrhythmias, crossover, and all-cause mortality.
This is a single-blinded study of 100 patients randomized to a strategy of His-Purkinje conduction system pacing Optimized Trial of Cardiac Resynchronization Therapy (HOT-CRT) versus biventricular pacing using coronary sinus (CS) lead (BVP). Both treatment options use standard-of-care, FDA-approved devices. The distinction is only in the allocation toward HOT-CRT and BVP. Treating physicians will be aware of assignment in order to facilitate routine device follow-up. Echocardiographic and electrocardiographic evaluation will also be performed in a blinded manner.
Cross-over is permitted between treatment group allocation if:
CS lead cannot be placed due to difficult cannulation of the CS, limited branches at the posterolateral or lateral wall, or phrenic nerve capture. These subjects may then cross-over to HOT-CRT.
HOT-CRT subjects may cross-over if His or left bundle pacing lead cannot be positioned with adequate stability and reasonable pacing output, or if optimal QRS narrowing cannot be achieved.
Implant procedure will be per routine percutaneous access, as is standard for pacemaker and Implantable Cardioverter Defibrillators (ICDs). . All subjects will receive an FDA-approved cardiac resynchronization therapy pacemaker or defibrillator device, as per standard of care outlined for the subject.
Follow-up will be performed at 2 weeks post-implant for incision check and device interrogation as is standard of care. In addition, routine device and clinical follow-up will be scheduled at 3 and 6 months. Electrocardiography (ECG) will be performed pre-implant, prior to hospital discharge, at 3 months, and 6 months. Echocardiography will be performed pre-implant and 6 months to evaluate for change in Left Ventricular Ejection Fraction (LVEF), chamber dimensions, volumes, and change in Left Ventricular (LV) end systolic volume index as is standard of care in the treatment of patients with advanced heart failure. New York Heart Association (NYHA) functional class and quality of life (utilizing the Kansas City Cardiomyopathy Questionnaire (KCCQ) and EQ 5D) will be assessed pre-implant and at 6 months.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HOT-CRT | Active Comparator | Subjects randomized to HOT-CRT will undergo CRT as described below. His bundle pacing lead will be placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and LV timing may be optimized to achieve maximal resynchronization. This will be at the discretion of the implanting physician. Only FDA approved leads and devices will be used. |
|
| Biventricular Pacing | Active Comparator | Subjects randomized to biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches.Only FDA approved leads and devices will be used. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HOT-CRT | Device | Subjects enrolled in the study will receive a permanent cardiac implantable electronic device (CIED) (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to HOT-CRT will have His bundle pacing lead placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and left ventricular timing may be optimized to achieve maximal resynchronization. |
| Measure | Description | Time Frame |
|---|---|---|
| Primary Endpoint | Improvement in left ventricular ejection fraction (LVEF) - change in LVEF% measured by 2D echo at 6 months compared to baseline | 6 months |
| Primary Safety | Freedom from major complications or need for CRT lead revision - complication such as lead dislodgment, pericardial tamponade, pneumothorax, systemic embolism, phrenic nerve stimulation not correctable by programming | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Secondary Composite | Crossover, ventricular tachycardia (VT)/ventricular fibrillation (VF), Heart failure hospitalization (HFH) or death | 6 months |
| Echocardiographic Response | change in LVEF >5% |
Not provided
Inclusion Criteria:
Patients at least 18 years of age
Diagnosis is NYHA Class II, III, and ambulatory Class IV heart failure with either ischemic or nonischemic cardiomyopathy and patients with NYHA Class I symptoms and ischemic cardiomyopathy, with at least one of the following:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Pugazhendhi Vijayaraman, MD | Geisinger Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Geisinger Health | Danville | Pennsylvania | 17822 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37715742 | Derived | Vijayaraman P, Pokharel P, Subzposh FA, Oren JW, Storm RH, Batul SA, Beer DA, Hughes G, Leri G, Manganiello M, Jastremsky JL, Mroczka K, Johns AM, Mascarenhas V. His-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy vs Biventricular Pacing: HOT-CRT Clinical Trial. JACC Clin Electrophysiol. 2023 Dec;9(12):2628-2638. doi: 10.1016/j.jacep.2023.08.003. Epub 2023 Sep 13. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Subjects were screened to meet inclusion/exclusion criteria pre consent and post consent, pre implant. In some cases, a repeat echo was scheduled to obtain ejection fraction (EF) measurement as part of inclusion/exclusion criteria, and result was pending at time of consent, therefore when resulted and patient no longer met inclusion criteria, they were screen failed.
Subjects will be recruited from Geisinger Wyoming Valley, Geisinger Medical Center, and Geisinger Community Medical Center. Investigators will identify eligible subjects, describe the study procedures and invite them to participate in the study. Informed Consent (ICF) will be provided to the subject and they will have ample time and opportunity to review and consider participation. Prior to performing any study procedures, the subject will sign the ICF and be considered enrolled at that point.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | BiV Pacing | Patients randomized to biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches |
| FG001 | HOT-CRT | Patients randomized to HOT-CRT will undergo CRT as described below. His bundle pacing lead will be placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and left ventricular (LV) timing may be optimized to achieve maximal resynchronization. This will be at the discretion of the implanting physician. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
50 patients randomized to BiV - 43 received BiV treatment 50 patients randomized to HOTCRT - 57 received HOTCRT treatment
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | HOT-CRT | Subjects randomized to HOT-CRT will undergo CRT as described below. His bundle pacing lead will be placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and LV timing may be optimized to achieve maximal resynchronization. This will be at the discretion of the implanting physician. Only FDA approved leads and devices will be used. HOT-CRT: Subjects enrolled in the study will receive a permanent cardiac implantable electronic device (CIED) (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to HOT-CRT will have His bundle pacing lead placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and left ventricular timing may be optimized to achieve maximal resynchronization. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Primary Endpoint | Improvement in left ventricular ejection fraction (LVEF) - change in LVEF% measured by 2D echo at 6 months compared to baseline | 50 patients randomized to BiV - 43 received BiV treatment 50 patients randomized to HOTCRT - 57 received HOTCRT treatment | Posted | Mean | Standard Deviation | percent ejection fraction | 6 months |
|
Adverse events (AE) were monitored through the patient's study participation (about 6 months) and throughout the course of the study.
An AE includes, but is not limited to, the following: Any clinically significant worsening of a preexisting condition. An AE occurring from abuse (e.g., use for nonclinical reasons) of a test article. An AE that has been associated with the discontinuation of the use of a test article.
50 patients randomized to BiV - 43 received BiV treatment 50 patients randomized to HOTCRT - 57 received HOTCRT treatment
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | HOT-CRT | Subjects randomized to HOT-CRT will undergo CRT as described below. His bundle pacing lead will be placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and LV timing may be optimized to achieve maximal resynchronization. This will be at the discretion of the implanting physician. Only FDA approved leads and devices will be used. HOT-CRT: Subjects enrolled in the study will receive a permanent cardiac implantable electronic device (CIED) (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to HOT-CRT will have His bundle pacing lead placed initially to achieve CRT. If complete resynchronization is achieved (BBB normalization) but capture thresholds are high (1.5-2V), the lead may be placed in the distal conduction system (left bundle branch area). If only partial QRS narrowing is achieved, a coronary sinus lead may be placed and left ventricular timing may be optimized to achieve maximal resynchronization. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Threshold increase >1 V | Cardiac disorders | Systematic Assessment |
Not provided
This was a small randomized pilot clinical trial performed in a single health system experienced in HOTCRT. This study was limited to 6 months of follow-up care and was not powered to detect differences in clinical outcomes. The study population was not diverse and included only a small number of women. Future large multicenter randomized controlled studies with longer follow-up times are needed for a comparison of long-term clinical outcomes between HOTCRT and BiV pacing.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Pugazhendhi Vijayaraman | Geisinger Health System | 5708086020 | 5444 | pvijayaraman1@geisinger.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 17, 2023 | Nov 27, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 7, 2020 | Nov 27, 2023 | ICF_001.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D009202 | Cardiomyopathies |
| D018487 | Ventricular Dysfunction, Left |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D018754 | Ventricular Dysfunction |
Not provided
Not provided
| ID | Term |
|---|---|
| D058406 | Cardiac Resynchronization Therapy |
| ID | Term |
|---|---|
| D002304 | Cardiac Pacing, Artificial |
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
Not provided
Not provided
Not provided
Not provided
Not provided
Subjects will be blinded to treatment arm. Echocardiographic evaluation will be performed by study physician blinded to lead placement
|
| Biventricular Pacing | Device | Subjects enrolled in the study will receive a permanent CIED (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to Biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches. |
|
| 6 months |
| BG001 | Biventricular Pacing | Subjects randomized to biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches.Only FDA approved leads and devices will be used. Biventricular Pacing: Subjects enrolled in the study will receive a permanent CIED (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to Biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Hypertension | Count of Participants | Participants |
|
| Diabetes | Count of Participants | Participants |
|
| Coronary Artery Disease | Count of Participants | Participants |
|
| Atrial fibrillation | Count of Participants | Participants |
|
| Chronic kidney disease | Count of Participants | Participants |
|
| Nonischemic cardiomyopathy | Count of Participants | Participants |
|
| Left bundle branch block | Count of Participants | Participants |
|
| Left ventricular ejection fraction | Mean | Standard Deviation | percent ejection fraction |
|
| QRS | Mean | Standard Deviation | ms |
|
| New York Heart Association (NYHA) functional class | New York Heart Association functional class Range: I-IV I-No limitation of physical activity. II-Slight limitation of physical activity III-Marked limitation of physical activity IV-Symptoms of heart failure at rest. Any physical activity causes further discomfort Higher value represents worse clinical condition | Mean | Standard Deviation | units on a scale |
|
| Medications | Count of Participants | Participants |
|
| OG001 | Biventricular Pacing | Subjects randomized to biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches.Only FDA approved leads and devices will be used. Biventricular Pacing: Subjects enrolled in the study will receive a permanent CIED (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to Biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches. |
|
|
| Primary | Primary Safety | Freedom from major complications or need for CRT lead revision - complication such as lead dislodgment, pericardial tamponade, pneumothorax, systemic embolism, phrenic nerve stimulation not correctable by programming | 50 patients randomized to BiV - 43 received BiV treatment 50 patients randomized to HOTCRT - 57 received HOTCRT treatment | Posted | Count of Participants | Participants | 6 months |
|
|
|
| Secondary | Secondary Composite | Crossover, ventricular tachycardia (VT)/ventricular fibrillation (VF), Heart failure hospitalization (HFH) or death | 50 patients randomized to BiV - 43 received BiV treatment 50 patients randomized to HOTCRT - 57 received HOTCRT treatment | Posted | Count of Participants | Participants | 6 months |
|
|
|
| Secondary | Echocardiographic Response | change in LVEF >5% | 50 patients randomized to BiV - 43 received BiV treatment 50 patients randomized to HOTCRT - 57 received HOTCRT treatment | Posted | Count of Participants | Participants | 6 months |
|
|
|
| 2 |
| 57 |
| 17 |
| 57 |
| 0 |
| 57 |
| EG001 | Biventricular Pacing | Subjects randomized to biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches.Only FDA approved leads and devices will be used. Biventricular Pacing: Subjects enrolled in the study will receive a permanent CIED (CRT-pacemaker or CRT-defibrillator) as clinically indicated. Subjects randomized to Biventricular pacing will undergo left ventricular lead placement in the coronary sinus venous branches. | 2 | 43 | 32 | 43 | 0 | 43 |
| Lead dislodgement | Cardiac disorders | Systematic Assessment |
|
| Stroke | Cardiac disorders | Systematic Assessment |
|
| Infection | Infections and infestations | Systematic Assessment |
|
| Late perforation into left ventricle | Cardiac disorders | Systematic Assessment |
|
| Cardiac tamponade | Cardiac disorders | Systematic Assessment |
|
| Phrenic nerve stimulation | Cardiac disorders | Systematic Assessment |
|
| Hematoma requiring evacuation | Surgical and medical procedures | Systematic Assessment |
|
| Secondary composite clinical endpoint | Cardiac disorders | Systematic Assessment | Heart failure hospitalization, treatment crossover, VT/VF requiring implantable cardioverter-defibrillator (ICD) therapy |
|
| Total | Cardiac disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided