Stereotactic Arrhythmia Radioablation for Ventricular Tachycardia (StAR-VT)

NCT05258422 | Enrolling By Invitation Phase 2 DMC

• 1 other identifier: 2022-7202
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

In 2017 a novel treatment approach to a series of 5 patients with refractory VT was introduced, using ablative radiation with a stereotactic body radiation therapy (SBRT) technique to arrhythmogenic scar regions defined by noninvasive cardiac mapping. More recently, Robinson et al. reported on the results of their Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia (ENCORE-VT) trial, also using a similar SBRT technique in a series of 17 patients with refractory VT. Both studies report a marked reduction in VT burden, a decrease in antiarrhythmic drug use, and an improvement in quality of life. Since then, numerous other centres have detailed their initial experience with this technique. These initial results suggest that this new treatment paradigm has the potential to improve morbidity and mortality for patients suffering from treatment-refractory VT by means of a minimally invasive technique, but requires further validation for widespread use. The appropriate dose for therapeutic effect of this new treatment is not well established as only a single dose prescription of 25 Gy in 1 fraction has been described with benefit. In this phase 2 trial, the investigators plan on expanding the experience with this technique but also by contributing to understanding the relationship between dose-effect relationship through a dose de-escalation stratification, to 20 Gy in 1 fraction, with the goal of minimizing possible adverse events and radiation dose to surrounding healthy tissue while maintaining a clinical benefit.

Conditions

Ventricular Tachycardia; Arrhythmia; Arrhythmic Storm; Radiation Toxicity

Keywords

stereotactic body radiotherapy, ventricular tachycardia

Outcome Measures

Primary Outcomes (3)

• Change in arrhythmia burden measured by the number of VT events

  Changes in arrhythmia burden measured by the number of VT events comparing the 12-month period after a single fraction of 20 Gy SBRT with a single fraction of 25 Gy in historical controls

  6 months and 12 months following study intervention

• Change in arrhythmia burden measured by the number of ICD events

  Changes in arrhythmia burden measured by the number of ICD events comparing the 12-month period after a single fraction of 20 Gy SBRT with a single fraction of 25 Gy in historical controls

  6 months and 12 months following study intervention

• Acute radiation toxicity within the first 90 days measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  Rate of severe adverse events at less than or equal to 90 days that were treatment related (possibly, probably, or definitely) as defined using the CTCAE v5.0

  90 days following study intervention.

Secondary Outcomes (4)

• Late radiation toxicity occurring after the first 90 days until 5 years measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  90 days - 5 years following study intervention

• Changes in number and doses of antiarrhythmic drugs

  1 year, 3 years, and 5 years following study intervention

• Patient-Reported Quality of life as measured by the short form-36 questionnaire

  6 months, 1 year, 3 years, and 5 years following study intervention

• Patient-Reported Quality of life as measured by the Arrhythmia-specific questionnaire in Tachycardia and arrhythmia (ASTA)

  6 months, 1 year, 3 years, and 5 years following study intervention

Other Outcomes (1)

• Overall Survival

  5 years following radiation therapy

Study Arms (1)

Radiation: 20 Gy in 1 fraction

EXPERIMENTAL

External beam, stereotactic body radiotherapy of 20 Gy delivered in 1 fraction to the planning target volume (PTV) of the arrhythmogenic substrate

Radiation: stereotactic body radiotherapy, 20 Gy in 1 fraction

Interventions

stereotactic body radiotherapy, 20 Gy in 1 fraction RADIATION

A single dose of focused radiation therapy of 20 Gy in 1 fraction to the PTV of the arrhythmogenic substrate

Also known as: stereotactic ablative radiotherapy, 20 Gy in 1 fraction

Radiation: 20 Gy in 1 fraction

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age
• Ishemic or non-ischemic cardiomyopathy
• Recurrent episodes of monomorphic ventricular tachycardia having failed standard treatment with at least 1 antiarrhythmic drug
• Previous endocardial and/or epicardial electrophysiology study and ablation.
• Participants who have a contraindication to electrophysiology studies (ventricular thrombus, absence of vascular access, valvular heart disease or mechanical heart valve that precludes left-ventricular access) may be eligible for the protocol provided the arrhythmic substrate can be defined through non-invasive methods.

You may not qualify if:

• Previous RT in the treatment field that precludes furth RT
• Active connective tissue disease
• Interstitial pulmonary fibrosis
• Pregnant or breastfeeding individuals
• Participants who plan to become pregnant or breast feed during the study duration

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

Cedars Cancer Center, McGill University Health Centre

Montreal, Quebec, H4A3J1, Canada

Location

Related Publications (19)

• AlKalbani A, AlRawahi N. Management of monomorphic ventricular tachycardia electrical storm in structural heart disease. J Saudi Heart Assoc. 2019 Jul;31(3):135-144. doi: 10.1016/j.jsha.2019.05.001. Epub 2019 May 11.

  PMID: 31198398 BACKGROUND

• Shenthar J. Unusual Incessant Ventricular Tachycardia: What Is the Underlying Cause and the Possible Mechanism? Circ Arrhythm Electrophysiol. 2015 Dec;8(6):1507-11. doi: 10.1161/CIRCEP.115.002886. No abstract available.

  PMID: 26671936 BACKGROUND

• Anderson RD, Ariyarathna N, Lee G, Virk S, Trivic I, Campbell T, Chow CK, Kalman J, Kumar S. Catheter ablation versus medical therapy for treatment of ventricular tachycardia associated with structural heart disease: Systematic review and meta-analysis of randomized controlled trials and comparison with observational studies. Heart Rhythm. 2019 Oct;16(10):1484-1491. doi: 10.1016/j.hrthm.2019.05.026. Epub 2019 May 29.

  PMID: 31150816 BACKGROUND

• Hohnloser SH, Kuck KH, Dorian P, Roberts RS, Hampton JR, Hatala R, Fain E, Gent M, Connolly SJ; DINAMIT Investigators. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med. 2004 Dec 9;351(24):2481-8. doi: 10.1056/NEJMoa041489.

  PMID: 15590950 BACKGROUND

• Aziz Z, Tung R. Novel Mapping Strategies for Ventricular Tachycardia Ablation. Curr Treat Options Cardiovasc Med. 2018 Mar 23;20(4):34. doi: 10.1007/s11936-018-0615-1.

  PMID: 29572643 BACKGROUND

• Cuculich PS, Schill MR, Kashani R, Mutic S, Lang A, Cooper D, Faddis M, Gleva M, Noheria A, Smith TW, Hallahan D, Rudy Y, Robinson CG. Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia. N Engl J Med. 2017 Dec 14;377(24):2325-2336. doi: 10.1056/NEJMoa1613773.

  PMID: 29236642 BACKGROUND

• Robinson CG, Samson PP, Moore KMS, Hugo GD, Knutson N, Mutic S, Goddu SM, Lang A, Cooper DH, Faddis M, Noheria A, Smith TW, Woodard PK, Gropler RJ, Hallahan DE, Rudy Y, Cuculich PS. Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia. Circulation. 2019 Jan 15;139(3):313-321. doi: 10.1161/CIRCULATIONAHA.118.038261.

  PMID: 30586734 BACKGROUND

• Walfridsson U, Arestedt K, Stromberg A. Development and validation of a new Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) with focus on symptom burden. Health Qual Life Outcomes. 2012 Apr 30;10:44. doi: 10.1186/1477-7525-10-44.

  PMID: 22545926 BACKGROUND

• Knutson NC, Samson PP, Hugo GD, Goddu SM, Reynoso FJ, Kavanaugh JA, Mutic S, Moore K, Hilliard J, Cuculich PS, Robinson CG. Radiation Therapy Workflow and Dosimetric Analysis from a Phase 1/2 Trial of Noninvasive Cardiac Radioablation for Ventricular Tachycardia. Int J Radiat Oncol Biol Phys. 2019 Aug 1;104(5):1114-1123. doi: 10.1016/j.ijrobp.2019.04.005. Epub 2019 Apr 16.

  PMID: 31002942 BACKGROUND

• Duane F, Aznar MC, Bartlett F, Cutter DJ, Darby SC, Jagsi R, Lorenzen EL, McArdle O, McGale P, Myerson S, Rahimi K, Vivekanandan S, Warren S, Taylor CW. A cardiac contouring atlas for radiotherapy. Radiother Oncol. 2017 Mar;122(3):416-422. doi: 10.1016/j.radonc.2017.01.008. Epub 2017 Feb 21.

  PMID: 28233564 BACKGROUND

• Hanna GG, Murray L, Patel R, Jain S, Aitken KL, Franks KN, van As N, Tree A, Hatfield P, Harrow S, McDonald F, Ahmed M, Saran FH, Webster GJ, Khoo V, Landau D, Eaton DJ, Hawkins MA. UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy. Clin Oncol (R Coll Radiol). 2018 Jan;30(1):5-14. doi: 10.1016/j.clon.2017.09.007. Epub 2017 Oct 13.

  PMID: 29033164 BACKGROUND

• Desai MY, Windecker S, Lancellotti P, Bax JJ, Griffin BP, Cahlon O, Johnston DR. Prevention, Diagnosis, and Management of Radiation-Associated Cardiac Disease: JACC Scientific Expert Panel. J Am Coll Cardiol. 2019 Aug 20;74(7):905-927. doi: 10.1016/j.jacc.2019.07.006.

  PMID: 31416535 BACKGROUND

• Pinta C, Besse R. Stereotactic ablative body radiotherapy for ventricular tachycardia: An alternative therapy for refractory patients. Anatol J Cardiol. 2021 Dec;25(12):858-862. doi: 10.5152/AnatolJCardiol.2021.187.

  PMID: 34866579 BACKGROUND

• Gerard IJ, Bernier M, Hijal T, Kopek N, Pater P, Stosky J, Stroian G, Toscani B, Alfieri J. Stereotactic Arrhythmia Radioablation for Ventricular Tachycardia: Single Center First Experiences. Adv Radiat Oncol. 2021 Apr 20;6(4):100702. doi: 10.1016/j.adro.2021.100702. eCollection 2021 Jul-Aug. No abstract available.

  PMID: 34095614 BACKGROUND

• Lee J, Bates M, Shepherd E, Riley S, Henshaw M, Metherall P, Daniel J, Blower A, Scoones D, Wilkinson M, Richmond N, Robinson C, Cuculich P, Hugo G, Seller N, McStay R, Child N, Thornley A, Kelland N, Atherton P, Peedell C, Hatton M. Cardiac stereotactic ablative radiotherapy for control of refractory ventricular tachycardia: initial UK multicentre experience. Open Heart. 2021 Nov;8(2):e001770. doi: 10.1136/openhrt-2021-001770.

  PMID: 34815300 BACKGROUND

• Chiu MH, Mitchell LB, Ploquin N, Faruqi S, Kuriachan VP. Review of Stereotactic Arrhythmia Radioablation Therapy for Cardiac Tachydysrhythmias. CJC Open. 2020 Nov 13;3(3):236-247. doi: 10.1016/j.cjco.2020.11.006. eCollection 2021 Mar.

  PMID: 33778440 BACKGROUND

• Sharma A, Wong D, Weidlich G, Fogarty T, Jack A, Sumanaweera T, Maguire P. Noninvasive stereotactic radiosurgery (CyberHeart) for creation of ablation lesions in the atrium. Heart Rhythm. 2010 Jun;7(6):802-10. doi: 10.1016/j.hrthm.2010.02.010. Epub 2010 Feb 13.

  PMID: 20156591 BACKGROUND

• Blanck O, Bode F, Gebhard M, Hunold P, Brandt S, Bruder R, Grossherr M, Vonthein R, Rades D, Dunst J. Dose-escalation study for cardiac radiosurgery in a porcine model. Int J Radiat Oncol Biol Phys. 2014 Jul 1;89(3):590-8. doi: 10.1016/j.ijrobp.2014.02.036. Epub 2014 Apr 18.

  PMID: 24751407 BACKGROUND

• Amino M, Yoshioka K, Fujibayashi D, Hashida T, Furusawa Y, Zareba W, Ikari Y, Tanaka E, Mori H, Inokuchi S, Kodama I, Tanabe T. Year-long upregulation of connexin43 in rabbit hearts by heavy ion irradiation. Am J Physiol Heart Circ Physiol. 2010 Mar;298(3):H1014-21. doi: 10.1152/ajpheart.00160.2009. Epub 2010 Jan 8.

  PMID: 20061548 BACKGROUND

Related Links

• CTCAE v5.0

MeSH Terms

Conditions

Tachycardia, Ventricular; Arrhythmias, Cardiac; Radiation Injuries

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Tachycardia; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Joanne Alfieri, MD

  MUHC division of radiation oncology/RIMUHC

  PRINCIPAL INVESTIGATOR

• Martin L Bernier, MD

  MUHC division of cardiology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Radiation Oncology

Model Details: This study will assess the non-inferiority of treatment with single fraction of 20 Gy delivered with stereotactic body radiotherapy in comparison with historical controls treated with a single fraction of 25 Gy. Based on historical controls, the investigators anticipate an incidence rate of approximately five VT events per person-year in participants treated with 25 Gy historical comparator. Based on a Poisson distribution and using a non-inferiority margin of 8.5 events per-year (corresponding to an incident rate ratio of 1.7), recruitment of nine participants will provide 80% power when using a one-sided type I error set at 0.05.

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: February 28, 2022
• Study Start: July 1, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2031
• Last Updated: March 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)