SBRT in Chagas Disease Ventricular Tachycardia

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Brief Title

SBRT in Chagas Disease Ventricular Tachycardia

Official Title

Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia in Chagas Disease Patients

Brief Summary

      This is an observational study of 10 Chagas Disease patients with Ventricular Tachycardia
      that have failed prior catheter ablation or have this procedure contraindicated due to
      clinical status. Those patients will underwent to Stereotactic Body Radiation Therapy (SBRT)
      targeting the area of the heart of the VT circuits. Radioablation target will be defined
      based on prior ablation electroanatomical mapping, VT morphology, pre-acquired imaging (CT
      angiogram, Cardiac Magnetic Resonance), current imaging reconstructed and integrated to
      electroanatomical mapping and a EP study to define current VT morphologies. Gross targeted
      volume (GTV), internal targeted volume (ITV) and planning targeted volume (PTV) will be
      defined and calculated and a single 25Gy dose will be delivered to the PTV. Patients will be
      followed initially for one year and efficacy endpoint will be rate of VT recurrence, time to
      recurrence and VT burden. Safety endpoint will be the occurrence of any adverse effect
      related to SBRT.
    

Detailed Description

      Enrollment A patient that fulfill all inclusion criteria (especially diagnosis of Chagas
      heart disease including positive serology, recurrent sustained ventricular tachycardia
      requiring therapy and failed or is ineligible for catheter ablation and had no exclusion
      criteria will be identified as a candidate for participation in this study while receiving
      care at Instituto do Coração, São Paulo, Brazil. The clinical team will contact the patient
      in-person and propose study participation and Consent Form will be applied.

      A total of 10 patients will be enrolled in the current study. At the time of enrollment,
      baseline information pertaining to symptoms and details regarding clinical presentation,
      imaging, and heart catheterization procedures will be obtained from examination of their
      medical record and recorded in a Redcap database.

      Pre-radiation Imaging and Definition of Treatment Area:

      All patients will perform a cardiac MRI with 3D LGE sequence to be imported in the ADAS 3D
      software. After MRI acquisition, images will be imported in the software, segmented and the
      channels will be identified using an specific tool in the software. After channels and scar
      identified the quality of reconstruction and channel identification will be manually
      validated by one of the investigators. If the image is considered adequate, the scar, the
      chambers and the channels will be exported in VTK format. If the reconstruction is defined as
      a poor quality by the investigators, last VT ablation procedure and or ECGs of the VT and
      cardiac, mapping data from prior ablation, prior MRI or cardiac CT analyzing wall thickness
      will be used to design treatment area . Additionally, areas of scar or infarction identified
      by previous electroanatomic mapping (voltage maps), imaging (CT, echocardiography, and/or
      nuclear imaging) that are likely the source of VT based on mapping or ECG analysis will be
      targeted. The area of interest will be determined by both the treating cardiologist and
      radiation oncologist.

      Radiation treatment:

      Simulation:

      All patients will undergo a 4D CT scan for treatment planning. The patient will be
      immobilized using a custom BodyFIX device. CT with contrast is preferred to facilitate
      anatomical definition when the patient is a candidate for contrast.

      Definition of the target volume:

      As described above, the gross target volume (GTV) will be defined using the pre-radiation
      imaging. Using the 4D CT data, an internal target volume (ITV) will then be created to
      account for organ motion. Finally, to account for any patient setup variability, a planning
      target volume (PTV) will be created by adding a 5 mm margin to the ITV. The prescribed dose
      will be 25 Gy to the PTV.

      The following are recommendations for radiation planning parameters with regards to target
      coverage and normal tissue constraints. Final determination regarding radiation treatment
      plan approval is left at the treating provider's discretion.

      Treatment planning guidelines:

        -  95% of the PTV should be covered with 100% of the prescribed dose

        -  100% of the ITV should be covered with 100% of the prescribed dose Dmax of 120% the
           prescribed dose SBRT will take place at the radiation oncology department. Treatment
           will be completed within approximately 90 minutes during one visit.

      Post ablation management Any ICD or pacemaker will be interrogated before and immediately
      after ablation and settings and function documented. Continued antiarrhythmic drug therapy
      will be left to the discretion of the treating physicians. The following approaches are
      recommended: If the patient is receiving amiodarone, it is recommended that the dose be
      reduced to 200 mg daily and then consider stopping it after 3 months if no VT has occurred in
      the previous month. It is recommended that antiarrhythmic drugs combined with amiodarone be
      stopped at 6 weeks after radioablation if VT has not recurred in the preceding two weeks. For
      other antiarrhythmic medications in the absence of amiodarone, continuing administration for
      the first 3 months is recommended if tolerated.

      Anticoagulation with warfarin or a direct acting anticoagulant will be maintained for one
      month.

      Follow-up Follow up will be at 4-6 weeks, 10-14weeks, 5-7 months, 11-13 months and thereafter
      every 1 year. At the above intervals, all patients will return for follow-up in the
      Department of Cardiology and Department of Radiation Oncology. At each visit screening for
      effectiveness and adverse effects attributable to treatment will be performed. Arrhythmia
      burden will be determined from ICD interrogation. Ventricular function will be assessed from
      echocardiography at 3 months. Side effects will be graded according to CTCAE v4.0 criteria.

      Patients who die during the follow-up period will be considered for autopsy to evaluate the
      effect of treatment at the histologic and cellular level. This will be subject to approval by
      the patient or his/her family.

      Risks The principal elements of risk in the study are possible complications of ablative
      doses of radiation targeting the ventricle. Target regions and radiation doses will be
      designed to limit dose to surrounding normal tissues using established constraints to
      minimize potential toxicity. Treatment experience for an electrically ablative dose of
      radiation to the myocardium is based on case reports and series noted above. Potential side
      effects include, but are not limited to, skin changes/fibrosis, rib weakening or fracture,
      lung injury (pneumonitis or fibrosis), heart injury (decreased EF, pericarditis, or
      conduction abnormalities), vascular injury (to coronaries or other major vessels), nerve or
      spinal injury, esophageal injury (stricture or esophagitis), fatigue, birth defects, and
      secondary malignancy.

      Given the severe detriment to quality of life and survival in patients with recurrent VT and
      the evidence of VT burden reduction in patients treated with stereotactic ablation, we
      believe the benefits of further characterizing this technique justify the risks.

      Reporting of Adverse Events or Unanticipated Problems involving Risk to Participants or
      Others Any unanticipated adverse events will be reported by the Principal Investigator
      according to applicable IRB policy. The PI is fully engaged in the actual performance of the
      study and this ensures that adverse events would be readily known and reported by the PI.

      Study Withdrawal/Discontinuation If an individual decides to withdraw their consent by
      informing study staff in writing or verbally, we will withdraw the participant. Contact
      information for the PI and study staff will be made available to the participant upon
      enrollment in the consent document.

      Data Management Data will be stored in REDCap using the participant's study ID. Their REDCap
      data record may contain some identifying information. Subjects will be tracked using their
      study ID. The identifiable data, excluding date of procedures, will reside as a separate form
      under the data entry sections labeled "Registration/PHI" within our REDCap database which
      will allow us to exclude access to the identifiable information, excluding date of
      procedures, if necessary. Minimal paper records will be kept, and they will be kept locked in
      a cabinet.

      Study protocol will adhere to privacy regulations at Instituto do Coração. No information
      will be released, nor will participation in the research be acknowledged, to any party except
      where compulsory according to law or Instituto do Coração policy. There may be unknown or
      unanticipated adverse effects from participation in this registry for which the PI and study
      team will remain observant.

      12. Follow-up and Record Retention Patient will be enrolled until the number is complete.
      Data will be retained indefinitely. Electronic data may be destroyed earlier at the request
      of the participant. Electronic records will be deleted from the REDCap database, paper copies
      will be deposited into locked containers designated for shredding of confidential patient
      information.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Safety of SBRT for the treatment of Ventricular Tachycardia

Secondary Outcome

 Time to VT Recurrence

Condition

Ventricular Tachycardia

Intervention

Stereotactic Body Radiation Therapy

Study Arms / Comparison Groups

 Stereotactic Body rRadiotherapy (SBRT)
Description:  SBRT targeting the area of the circuit of Ventricular Tachycardia

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Radiation

Estimated Enrollment

10

Start Date

July 14, 2021

Completion Date

July 31, 2023

Primary Completion Date

July 31, 2022

Eligibility Criteria

        Inclusion Criteria:

          1. Diagnosis of Chagas heart disease including positive serology

          2. Recurrent sustained ventricular tachycardia requiring therapy due to symptoms, ICD
             shocks, or requiring hospitalization.

          3. Age>18 years.

          4. Able to give written, informed consent. If the patient requires continuous
             sedation/anesthesia for arrhythmia control consent can be provided by the next of kin.

          5. Medically fit to undergo radiation planning and treatment sessions.

          6. Failed antiarrhythmic medications due to VT recurrence, drug intolerance, or
             contraindication.

          7. Failed prior catheter ablation due to arrhythmia recurrence or ineligible for
             endocardial or epicardial catheter ablation (LV thrombus, epicardial adhesion,
             megacolon, prior open chest surgery)

        Exclusion Criteria:

          1. Cardiogenic shock not due to VT with no possibility of heart transplant or ventricular
             assist device.

          2. Inability for patient to be adequately immobilized for radiation planning and
             treatment.

          3. Repeat catheter ablation is felt to be a reasonable option.

          4. Previous radiation to the chest.

          5. Pregnancy or refusal to use contraception.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Mauricio I Scanavacca, MD, PhD, +551126615341, [email protected]

Location Countries

Brazil

Location Countries

Brazil

Administrative Informations


NCT ID

NCT04984265

Organization ID

4920/19/139


Responsible Party

Principal Investigator

Study Sponsor

University of Sao Paulo General Hospital


Study Sponsor

Mauricio I Scanavacca, MD, PhD, Study Director, University of São Paulo General Hospital


Verification Date

July 2021