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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertrophic Cardiomyopathy
• Intervention / Treatment: Device: Stereotactic body radiation therapy

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Costas O'Mahony, FRCP, MD; Email: constantinos.omahony@nhs.net

Study Locations

• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Barts Heart Centre
    • Contact: Costas O'Mahony, FRCP, MD; Email: constantinos.omahony@nhs.net
    • Sub-Investigator: Dan Jones, MRCP PhD
    • Sub-Investigator: Charles Knight, FRCP, MD
    • Principal Investigator: Costas O'Mahony, FRCP, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 βHCG negative and on contraception
6. Lack of cardiac device with anti-bradycardia pacing capabilities
7. Previous chest radiotherapy
8. Inability to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stereotactic body radiation therapy; In patients with HCM and refractory symptoms from LVOTO, stereotactic body radiation therapy will be delivered locally to relieve symptoms	Device: Stereotactic body radiation therapy; Stereotactic body radiation therapy delivered to reduce LVOTO in patients with HCM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of MACE endpoints	MACE = death, heart failure, myocardial infarction and stroke	3, 6 and 12 months
Change in aortic valve and mitral valve function	Echocardiography assessed aortic and mitral valve function	3, 6 and 12 months
Left anterior descending artery patency	Patency of left anterior descending artery with cardiac CT	12 months
Presence of radiation pneumonitis	Presence of radiation pneumonitis on CT	12 months
Development of complete heart block, atrial or ventricular arrhythmias	Cardiac device (ICD or pacemaker) check	3, 6 and 12 months
Change in LVOT gradient	Assessed with transthoracic echocardiography using same loading conditions as baseline	3, 6 and 12 months
Change in functional class	Change in NYHA and CCS class from baseline	6 and 12 months
Change in frequency of syncope and pre-syncope	Baseline to 6 and 12 months	6 and 12 months
Change in exercise capacity	6 minute Walk Test	6 and 12 months compared to Baseline
Change in health status	EQ-5D-5L	6 and 12 months compared to Baseline
Troponin T elevation	Measurement of Trop T	1,2,3 days post ablation
Change in LV wall thickness	CMR assessed thickness	6 months
Left ventricular ejection fraction (LVEF)	Measured on echocardiography	3, 6 and 12 months

Collaborators and Investigators

• Sponsor: Barts & The London NHS Trust
• Collaborators: Barts Cardiovascular CTU (Queen Mary University of London)
• Investigators: Principal Investigator: Costas O'Mahony, FRCP, MD, Barts & The London NHS Trust

Study record dates

Study Major Dates

• Study Start (Anticipated): January 2, 2020
• Primary Completion (Anticipated): January 2, 2022
• Study Completion (Anticipated): January 2, 2023

Study Registration Dates

• First Submitted: November 4, 2019
• First Submitted That Met QC Criteria: November 5, 2019
• First Posted (Actual): November 6, 2019

Study Record Updates

• Last Update Posted (Actual): November 6, 2019
• Last Update Submitted That Met QC Criteria: November 5, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Hypertrophy; Cardiomyopathies; Cardiomyopathy, Hypertrophic
• Other Study ID Numbers: NIRA-HOCM 1.1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No