NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Early Feasibility Study

Aortic Valve Stenosis Clinical Trial

Official title:

NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Early Feasibility Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06269640
• Other study ID #: 10001640
• Secondary ID: 001640-H
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 19, 2024
• Est. completion date: October 1, 2027

Study information

• Verified date: February 12, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Annette Stine, R.N.
• Phone: (301) 402-5558
• Email: stinea[@]nhlbi.nih.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background: Some people have a condition in which the wall (septum) that separates the two main pumping chambers of the heart is too thick. This thick septum causes a condition called "left ventricular outflow tract obstruction" (LVOTO), which reduces blood flow out of the heart. LVOTO can cause serious heart disease; symptoms may include shortness of breath, chest pain, heart failure, or death. Researchers want to find better ways to treat LVOTO. Objective: To test a new procedure where excess tissue is sliced away from the septum in people with LVOTO. This procedure is called "septal scoring along midline endocardium" (SESAME). Eligibility: Adults aged 21 years with LVOTO. Design: Participants will have baseline tests. They will have imaging scans and tests of their heart structure and function. They will take a walking test and answer questions about how their heart condition affects their life. Participants will stay in the hospital 2 to 6 days for the SESAME procedure. They will be completely or partially asleep for the procedure. A tube will be inserted into the mouth and down the throat to take pictures of the heart. Pictures may also be taken with a tube inserted inside the heart. Next, tubes will be inserted into the groin and guided through the blood vessels up to the heart. Guidewires will be inserted into the heart. Doctors will watch the path the wires take with x-rays and ultrasound. When the wire is in the correct place, it will be electrified to slice excess tissue away from the septum. Participants will have 3 follow-up visits within 1 year.

Description:

Cardiac interventricular septal reduction therapies - to relieve left ventricular outflow tract obstruction from transcatheter valve replacement or hypertrophic cardiomyopathy - have inherent limitations including dependence on coronary anatomy, high pacemaker implantation rate, and surgical morbidity. We developed a novel transcatheter ventricular myotomy called SEptal Scoring Along the Midline Endocardium (SESAME) that relies on intramyocardial guidewire navigation and transcatheter electrosurgery. SESAME has been performed on a small number of patients using off label devices. This study systematically characterizes the safety and early feasibility of SESAME at 1 enrolling site. SESAME is performed as septal reduction therapy in a heterogeneous group of subjects, including symptomatic hypertrophic cardiomyopathy and resting or provoked left ventricular outflow obstruction (LVOTO); and severe symptomatic mitral and/or aortic valve disease at high risk of standard heart surgical therapy and requiring later transcatheter heart valve implantation combined with manifest or potential LVOTO. A key goal of this study is to attempt to capture generalizable knowledge from as many patients as possible, and to add a limited number of research procedures to characterize the safety and provisional effectiveness of SESAME. Absent realistic non-clinical models of HCM or LVH combined with aortomitral disease, we believe little more information can be gleaned without clinical investigation.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: October 1, 2027
• Est. primary completion date: October 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 99 Years

Eligibility

• INCLUSION CRITERIA:

In order to be eligible to participate in the study, candidates must meet all of the

following criteria:

• Adults age >= 21 years
• Requires debulking of left ventricular septum for one of three phenotypes
• 1: Hypertrophic cardiomyopathy; OR
• 2: Left ventricular septal hypertrophy, mitral valve disease and/or aortic valve stenosis warranting/following transcatheter heart valve implantation, WITH intracameral gradient >= (30mmHg peak while resting; 50mmHg peak when provoked); OR
• 3: Left ventricular septal hypertrophy, mitral valve disease warranting transcatheter heart valve implantation, and risk of iatrogenic left ventricular outflow tract obstruction (LVOTO), Neo-LVOT <= 200 mm^2, WITHOUT intracameral gradient >= (30mmHg peak while resting; 50mmHg peak when provoked)
• Septal diastolic thickness on CT:
• Total >=12 mm, and
• Predicted residual septal thickness >= 6 mm, and
• Predicted laceration depth >= 6 mm
• Severely symptomatic, any of
• NYHA Class III or greater
• Canadian Angina Class CCS III or greater
• Explicitly chooses investigational SESAME over conventional treatment approaches including (1) cardiac myosin inhibitor therapy, if eligible (HCM only); (2) transcoronary alcohol septal ablation, if eligible; or (3) surgical left ventricular myotomy and/or myectomy, if eligible
• Concurrence of the multidisciplinary institutional heart team that the candidate is at high risk for surgical myectomy
• Concurrence of the study Central Clinical Eligibility Committee
• Willing to return for all scheduled follow-up activities, and eligible or able to undergo required protocol and testing Additional selection criteria for Hypertrophic Cardiomyopathy
• High risk of surgical myotomy/myectomy according to the multidisciplinary heart team EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation

in this study:

• Does not consent to participate, or unable to consent to participate
• Requires antegrade SESAME access (because of mechanical aortic valve)
• Prior completed transcoronary alcohol septal ablation, or prior surgical myectomy
• Pregnant
• Hemodynamic instability or emergency procedure
• eGFR < 30 mL/min/1.73m^2
• Survival despite successful procedure expected < 12months

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Hypertrophic Cardiomyopathy
• Hypertrophy
• Mitral Valve Disease

Intervention

Device:
• Septal Scoring Along Midline Endocardium
Transcatheter ventricular myotomy called SEptal Scoring Along the Midline Endocardium (SESAME) that relies on intramyocardial guidewire navigation and transcatheter electrosurgery

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Technical success	The primary feasibility endpoint is Technical success (measured at exit from the catheterization laboratory). All of the following must be present:-Alive-Procedure success including-Successful myocardial entry, navigation, and snaring of guidewire traversal system; and -Successful laceration of septal myocardium	1 day
Primary	Safety	Safety is measured as freedom from all of the following:-All-cause mortality-All stroke (disabling and non-disabling)-Major cardiac structural complication requiring intervention (such as iatrogenic ventricular septal defect, iatrogenic aortic valve regurgitation, iatrogenic mitral regurgitation, or pericardial tamponade) related to SESAME	30 days
Secondary	Complete heart block requiring permanent pacemaker	Complete heart block requiring permanent pacemaker	Discharge