Stereotactic Arrhythmia Radioablation for Ventricular Tachycardia (StAR-VT)

Ventricular Tachycardia Clinical Trial

— StAR-VT  

Official title:

Stereotactic Arrhythmia Radioablation for Ventricular Tachycardia (StAR-VT): a Single Centre, Phase II, Dose De-escalation, Non-inferiority, Clinical Trial.

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05258422
• Other study ID #: 2022-7202
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: July 1, 2023
• Est. completion date: December 31, 2031

Study information

• Verified date: May 2024
• Source: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Ventricular tachycardia (VT) is a potentially life-threatening arrhythmia characterized by electrical re-entry within patches of heterogeneous myocardial fibrosis leading to sustained consecutive ventricular beats at a rate > 100 per minute. VT is classified based on hemodynamic stability, duration (less than or greater than 30 seconds), morphology (monomorphic or polymorphic), and mechanism (scar-related re-entry, automaticity, triggered activity.

In patients with monomorphic VT, implantable cardioverter-defibrillators (ICDs) have become the cornerstone of therapy in decreasing mortality, through the prevention of sudden death from potentially lethal sustained arrhythmia in select patients. However, ICDs have no effect on the underlying arrhythmogenic substrate or fibrotic scar and thus are primarily a symptom-control therapy; patients may develop recurrent and debilitating shocks associated with an increase in mortality. Currently, catheter ablation (CA) for VT is used as an adjunctive therapy for patients who are refractory to medical therapy. A recent systematic review and meta-analysis of randomized controlled trials and observation studies comparing medical therapy and catheter ablation for VT shows that CA is superior to medical therapy for scar-related VT with respect to VT recurrence and the life-threatening VT storm. Despite this, there is still a high reported incidence of VT recurrence in both medically-treated (48%) and ablation-treated (39%) patients, suggesting that the current treatment paradigm is suboptimal for good control of this debilitating arrhythmia.

In 2017, Cuculich et al. introduced a novel treatment approach to a series of 5 patients with refractory VT, 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. These initial results suggest that this new treatment paradigm has the potential to vastly improve morbidity and mortality for patients suffering from VT by means of a minimally invasive technique, but requires further validation for widespread use.

Additionally, 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 9
• Est. completion date: December 31, 2031
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Arrhythmia
• Arrhythmias, Cardiac
• Radiation Toxicity
• Tachycardia
• Tachycardia, Ventricular
• Ventricular Tachycardia

Intervention

Radiation:
• stereotactic body radiotherapy, 20 Gy in 1 fraction
A single dose of focused radiation therapy of 20 Gy in 1 fraction to the PTV of the arrhythmogenic substrate

Locations

Country	Name	City	State
Canada	Cedars Cancer Center, McGill University Health Centre	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
McGill University Health Centre/Research Institute of the McGill University Health Centre

Country where clinical trial is conducted

Canada, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Int J Radiat Oncol Biol Phys. 2014 Dec 1;90(5):1264. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall Survival	The overall survival of participants following the intervention	5 years following radiation therapy
Primary	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
Primary	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
Primary	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	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	Severe adverse events as defined by CTCAE v5.0 occuring after the first 90 days following treatment	90 days - 5 years following study intervention
Secondary	Changes in number and doses of antiarrhythmic drugs	Changes in number and doses of all antiarrhythmic drugs that are used before and in the 5 year follow-up after the study intervention	1 year, 3 years, and 5 years following study intervention
Secondary	Patient-Reported Quality of life as measured by the short form-36 questionnaire	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
Secondary	Patient-Reported Quality of life as measured by the Arrhythmia-specific questionnaire in Tachycardia and arrhythmia (ASTA)	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

External Links

•   CTCAE v5.0