Non-Invasive Radiation Ablation in Patients With Hypertrophic CardioMyopathy: NIRA-HOCM

Hypertrophic Cardiomyopathy Clinical Trial

— NIRA-HOCM  

Official title:

Non-Invasive Radiation Ablation for Septal Reduction in Patients With Hypertrophic Obstructive CardioMyopathy: First in Man Pilot Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04153162
• Other study ID #: NIRA-HOCM 1.1
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2, 2020
• Est. completion date: January 2, 2023

Study information

• Verified date: November 2019
• Source: Barts & The London NHS Trust
• Contact: Mervyn Andiapen
• Phone: 02037658707
• Email: mervyn.andiapen[@]nhs.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Hypertrophic cardiomyopathy (HCM) is a common disease of the heart which causes thickening of the heart muscle.

HCM primarily affects the muscle of the main pumping chamber of the heart (the left ventricle) and particularly the septum (this is the muscular wall which separates the right and left side of the heart). In a subgroup of patients, the thickened heart muscle at the septum prevents blood from leaving the heart during contraction (this is called obstruction). This form of the disease is called hypertrophic obstructive cardiomyopathy (HOCM).

HOCM is a common cause of shortness of breath, chest pain and dizzy spells. These symptoms are treated with tablets and if symptoms are uncontrolled, patients are often offered invasive treatment to get rid of some of the thick heart muscle and reduce obstruction. This is achieved either by:

1. open heart surgery (myectomy) where a surgeon cuts out the thick muscle

2. injection of alcohol to the thick heart muscle via a tube in the wrist or groin (alcohol septal ablation). The alcohol thins the heart muscle at the point of obstruction, mimicking the effects of myectomy.

Unfortunately, some patients are not suitable for both these procedures.

This study will test whether radiotherapy, usually used for the treatment of tumours, can be used to destroy the thick heart muscle at the point of obstruction safely and effectively. Study patients will be monitored following the procedure and the investigators plan to measure the levels of heart muscle thinning, reduction of obstruction and improvement in symptoms and importantly document any side effects.

Radiotherapy works by precisely targeting high energy X-rays (ionising radiation) at a specific area of the body with the aim of destroying abnormal tissue. CyberKnife is one of the latest radiotherapy delivery systems, which will deliver highly focussed and accurate radiotherapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: January 2, 2023
• Est. primary completion date: January 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

1. Limiting, drug refractory symptoms secondary to left ventricular outflow tract obstruction

2. Previously failed invasive septal reduction therapy (ethanol septal ablation/surgical myectomy) or inability to perform invasive septal reduction due to increased risk/co-morbidities/anatomical considerations following specialist MDT review

3. A device (permanent pacemaker or implantable cardioverter defibrillator) in situ.

4. Ventricular septal thickness at site ablation = 16mm.

5. Patient able to tolerate lying flat for one hour

6. High target-surrogacy of ICD/pacing lead for cardiac motion (from cardiac-gated MRI or cardiac-gated CT with the patient in pacing mode used for treatment)

7. Successful completion of ICD lead tip tracking test ("patient dummy run") with the patient in pacing mode used for treatment

8. Adult Patients aged 18 and over willing and able to give written informed consent

Exclusion Criteria:

1. New York Heart Association I-II

2. Canadian Cardiovascular Society class 1-2

3. Follow-up impossible (e.g. no fixed abode)

4. Weight of patient that exceeds the maximum limit of CMR table (170kg)

5. Subjects of childbearing potential unless ßHCG negative and on contraception

6. Lack of cardiac device with anti-bradycardia pacing capabilities

7. Previous chest radiotherapy

8. Inability to provide informed consent.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Hypertrophic Cardiomyopathy
• Hypertrophy

Intervention

Device:
• Stereotactic body radiation therapy
Stereotactic body radiation therapy delivered to reduce LVOTO in patients with HCM

Locations

Country	Name	City	State
United Kingdom	Barts Heart Centre	London

Sponsors (3)

Lead Sponsor	Collaborator
Barts & The London NHS Trust	Barts Cardiovascular CTU (Queen Mary University of London), Barts Charity

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Demonstrate acute (= 90 days) safety of non-invasive SBRT.	The primary safety endpoint is defined as serious adverse events (SAEs) that are possibly/probably/definitely related to study treatment, based on previously published data for expected invasive alcohol septal-ablation procedures.	90 days
Secondary	Assessment of MACE endpoints	MACE = death, heart failure, myocardial infarction and stroke	3, 6 and 12 months
Secondary	Change in aortic valve and mitral valve function	Echocardiography assessed aortic and mitral valve function	3, 6 and 12 months
Secondary	Left anterior descending artery patency	Patency of left anterior descending artery with cardiac CT	12 months
Secondary	Presence of radiation pneumonitis	Presence of radiation pneumonitis on CT	12 months
Secondary	Development of complete heart block, atrial or ventricular arrhythmias	Cardiac device (ICD or pacemaker) check	3, 6 and 12 months
Secondary	Change in LVOT gradient	Assessed with transthoracic echocardiography using same loading conditions as baseline	3, 6 and 12 months
Secondary	Change in functional class	Change in NYHA and CCS class from baseline	6 and 12 months
Secondary	Change in frequency of syncope and pre-syncope	Baseline to 6 and 12 months	6 and 12 months
Secondary	Change in exercise capacity	6 minute Walk Test	6 and 12 months compared to Baseline
Secondary	Change in health status	EQ-5D-5L	6 and 12 months compared to Baseline
Secondary	Troponin T elevation	Measurement of Trop T	1,2,3 days post ablation
Secondary	Change in LV wall thickness	CMR assessed thickness	6 months
Secondary	Left ventricular ejection fraction (LVEF)	Measured on echocardiography	3, 6 and 12 months