Non-Invasive Radiation Ablation in Patients With Hypertrophic CardioMyopathy: NIRA-HOCM (NIRA-HOCM)
Primary Purpose
Hypertrophic Cardiomyopathy
Status
Unknown status
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Stereotactic body radiation therapy
Sponsored by
About this trial
This is an interventional treatment trial for Hypertrophic Cardiomyopathy
Eligibility Criteria
Inclusion Criteria:
- Limiting, drug refractory symptoms secondary to left ventricular outflow tract obstruction
- 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
- A device (permanent pacemaker or implantable cardioverter defibrillator) in situ.
- Ventricular septal thickness at site ablation ≥ 16mm.
- Patient able to tolerate lying flat for one hour
- 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)
- Successful completion of ICD lead tip tracking test ("patient dummy run") with the patient in pacing mode used for treatment
- Adult Patients aged 18 and over willing and able to give written informed consent
Exclusion Criteria:
- New York Heart Association I-II
- Canadian Cardiovascular Society class 1-2
- Follow-up impossible (e.g. no fixed abode)
- Weight of patient that exceeds the maximum limit of CMR table (170kg)
- Subjects of childbearing potential unless βHCG negative and on contraception
- Lack of cardiac device with anti-bradycardia pacing capabilities
- Previous chest radiotherapy
- Inability to provide informed consent.
Sites / Locations
- Barts Heart Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Stereotactic body radiation therapy
Arm Description
In patients with HCM and refractory symptoms from LVOTO, stereotactic body radiation therapy will be delivered locally to relieve symptoms
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Assessment of MACE endpoints
MACE = death, heart failure, myocardial infarction and stroke
Change in aortic valve and mitral valve function
Echocardiography assessed aortic and mitral valve function
Left anterior descending artery patency
Patency of left anterior descending artery with cardiac CT
Presence of radiation pneumonitis
Presence of radiation pneumonitis on CT
Development of complete heart block, atrial or ventricular arrhythmias
Cardiac device (ICD or pacemaker) check
Change in LVOT gradient
Assessed with transthoracic echocardiography using same loading conditions as baseline
Change in functional class
Change in NYHA and CCS class from baseline
Change in frequency of syncope and pre-syncope
Baseline to 6 and 12 months
Change in exercise capacity
6 minute Walk Test
Change in health status
EQ-5D-5L
Troponin T elevation
Measurement of Trop T
Change in LV wall thickness
CMR assessed thickness
Left ventricular ejection fraction (LVEF)
Measured on echocardiography
Full Information
NCT ID
NCT04153162
First Posted
November 4, 2019
Last Updated
November 5, 2019
Sponsor
Barts & The London NHS Trust
Collaborators
Barts Cardiovascular CTU (Queen Mary University of London)
1. Study Identification
Unique Protocol Identification Number
NCT04153162
Brief Title
Non-Invasive Radiation Ablation in Patients With Hypertrophic CardioMyopathy: NIRA-HOCM
Acronym
NIRA-HOCM
Official Title
Non-Invasive Radiation Ablation for Septal Reduction in Patients With Hypertrophic Obstructive CardioMyopathy: First in Man Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 2, 2020 (Anticipated)
Primary Completion Date
January 2, 2022 (Anticipated)
Study Completion Date
January 2, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Barts & The London NHS Trust
Collaborators
Barts Cardiovascular CTU (Queen Mary University of London)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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:
open heart surgery (myectomy) where a surgeon cuts out the thick muscle
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertrophic Cardiomyopathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Stereotactic body radiation therapy
Arm Type
Experimental
Arm Description
In patients with HCM and refractory symptoms from LVOTO, stereotactic body radiation therapy will be delivered locally to relieve symptoms
Intervention Type
Device
Intervention Name(s)
Stereotactic body radiation therapy
Intervention Description
Stereotactic body radiation therapy delivered to reduce LVOTO in patients with HCM
Primary Outcome Measure Information:
Title
Demonstrate acute (≤ 90 days) safety of non-invasive SBRT.
Description
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.
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Assessment of MACE endpoints
Description
MACE = death, heart failure, myocardial infarction and stroke
Time Frame
3, 6 and 12 months
Title
Change in aortic valve and mitral valve function
Description
Echocardiography assessed aortic and mitral valve function
Time Frame
3, 6 and 12 months
Title
Left anterior descending artery patency
Description
Patency of left anterior descending artery with cardiac CT
Time Frame
12 months
Title
Presence of radiation pneumonitis
Description
Presence of radiation pneumonitis on CT
Time Frame
12 months
Title
Development of complete heart block, atrial or ventricular arrhythmias
Description
Cardiac device (ICD or pacemaker) check
Time Frame
3, 6 and 12 months
Title
Change in LVOT gradient
Description
Assessed with transthoracic echocardiography using same loading conditions as baseline
Time Frame
3, 6 and 12 months
Title
Change in functional class
Description
Change in NYHA and CCS class from baseline
Time Frame
6 and 12 months
Title
Change in frequency of syncope and pre-syncope
Description
Baseline to 6 and 12 months
Time Frame
6 and 12 months
Title
Change in exercise capacity
Description
6 minute Walk Test
Time Frame
6 and 12 months compared to Baseline
Title
Change in health status
Description
EQ-5D-5L
Time Frame
6 and 12 months compared to Baseline
Title
Troponin T elevation
Description
Measurement of Trop T
Time Frame
1,2,3 days post ablation
Title
Change in LV wall thickness
Description
CMR assessed thickness
Time Frame
6 months
Title
Left ventricular ejection fraction (LVEF)
Description
Measured on echocardiography
Time Frame
3, 6 and 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Limiting, drug refractory symptoms secondary to left ventricular outflow tract obstruction
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
A device (permanent pacemaker or implantable cardioverter defibrillator) in situ.
Ventricular septal thickness at site ablation ≥ 16mm.
Patient able to tolerate lying flat for one hour
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)
Successful completion of ICD lead tip tracking test ("patient dummy run") with the patient in pacing mode used for treatment
Adult Patients aged 18 and over willing and able to give written informed consent
Exclusion Criteria:
New York Heart Association I-II
Canadian Cardiovascular Society class 1-2
Follow-up impossible (e.g. no fixed abode)
Weight of patient that exceeds the maximum limit of CMR table (170kg)
Subjects of childbearing potential unless βHCG negative and on contraception
Lack of cardiac device with anti-bradycardia pacing capabilities
Previous chest radiotherapy
Inability to provide informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mervyn Andiapen
Phone
02037658707
Email
mervyn.andiapen@nhs.net
First Name & Middle Initial & Last Name or Official Title & Degree
Costas O'Mahony, FRCP, MD
Email
constantinos.omahony@nhs.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Costas O'Mahony, FRCP, MD
Organizational Affiliation
Barts & The London NHS Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barts Heart Centre
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Costas O'Mahony, FRCP, MD
Email
constantinos.omahony@nhs.net
First Name & Middle Initial & Last Name & Degree
Mervyn Andiapen
Phone
02037658707
Email
mervyn.andiapen@nhs.net
First Name & Middle Initial & Last Name & Degree
Dan Jones, MRCP PhD
First Name & Middle Initial & Last Name & Degree
Charles Knight, FRCP, MD
First Name & Middle Initial & Last Name & Degree
Costas O'Mahony, FRCP, MD
12. IPD Sharing Statement
Plan to Share IPD
No
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Non-Invasive Radiation Ablation in Patients With Hypertrophic CardioMyopathy: NIRA-HOCM
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