Oesophageal Protection Study: A Multicentre Study. (IMPACT II)

Improving Oesophageal Protection During AF Ablation: a Multicentre Double-blind Randomized Clinical Trial.

Atrial fibrillation (AF) is a common debilitating heart rhythm condition that can cause heart failure and negatively impact a patient's outlook in terms of symptoms and disability. It is an irregular fast heart rhythm disorder coming from the top chamber of the heart (left atrium). Catheter ablation treatment has been shown to be effective in controlling or eliminating AF and its associated symptoms. This is now a common and effective treatment option for patients suffering with AF. During ablation, thermal energy is applied in the top chamber of the heart (the left atrium) to abolish abnormal electrical signals that cause AF. It is generally a safe procedure, but one potential risk associated with this procedure is damage to the oesophagus caused by thermal energy being transmitted to the oesophagus from the heart. The oesophagus sits just behind the heart chamber where ablation work is performed, about 5mm away, so it is vulnerable to damage. Although the risk of severe oesophageal damage is low, if it occurs it can be serious as the patient may become very ill as a result.

In a recent study, it was shown that a more advanced type of oesophageal probe that cools the oesophagus during ablation is better at protecting the oesophagus from ablation-related injury compared to the standard care probe currently used. As it was a single-centre study, more evidence is required before knowing if this type of probe is more effective in protecting the oesophagus.

The purpose is to run a multi-centre randomized study to compare the safety of AF ablation when there is protection by the oesophageal cooling probe versus the standard of care oesophageal temperature monitoring probe. This means that there is a 50:50 chance of the new cooling probe being used during AF ablation for participants.

Study Overview

• Status: Recruiting
• Conditions: Complication; AF - Atrial Fibrillation; Atrio-Esophageal Fistula
• Intervention / Treatment: Device: ensoETM. Esophageal cooling during AF ablation; Device: Esophageal temperature monitoring probe

Detailed Description

The purpose of this research project is to investigate the use of an oesophageal cooling probe as a new and potentially better method of oesophageal protection for AF ablation patients compared to standard care. This is the multi-centre version of the recently completed single-site study (IRAS ID: 253844). This multi-centre version is required to confirm if the oesophageal cooling probe is definitively superior to standard care in protecting AF ablation patients and to clarify the extent of this protection.

At present, the method of protection is limited; an oesophageal temperature monitoring probe is inserted whilst the patient is under general anaesthesia and the temperature is measured during ablation, stopping if temperatures markedly increase, which may suggest significant oesophageal thermal injury. This method is unreliable as the temperature probe does not sit well in the oesophagus and is often too far away from the area requiring monitoring. The probe is difficult to place as it can coil.

The design of the project is in the form of a randomised controlled trial like the single-centre study, so participants will have a 50:50 chance of being allocated to the study group receiving the new oesophageal cooling probe or the standard care (or control) group, receiving the oesophageal temperature monitoring probe.

The patient is blinded to the result of the randomization, to avoid bias/placebo effect.

If enrolled to the study group, the oesophageal cooling probe will be used- called the ensoETM probe. This is a smooth medical-grade silicone multi-lumen oesophageal probe (the device has a CE mark and is designed for the purpose of oesophageal insertion and cooling) that allows water irrigation in a closed loop system, when connected to an external console. If the console cools the irrigated water (this is controlled by manual up/down buttons depending on what temperature is desired), the oesophageal probe is then cooled also, which allows local oesophageal wall temperature to be controlled. Oesophageal cooling via the ensoETM probe can then counteract any transmitted thermal energy from the ablation. This probe is already in clinical use in critical care patients where it can control body temperature, if the probe is left in situ for purposely extended hours or days. It is therefore already known to be safe; it also has a good safety profile in the context of AF ablations based on experience from the single-centre study (IRAS ID: 253844; in press- doi:10.1093/europace/euaa276). In the single-centre study, all participants had endoscopic examination after their ablation to review the oesophagus, and no device/probe related abrasive trauma was seen.

The procedure is normally done under general anaesthetic so the participant will not be aware of this and will not be subjected to any sensation of pain or discomfort. The probe is soft and much gentler than the camera probe that the team normally have to insert during the catheter ablation procedure (the camera probe or transoesophageal echocardiography, TOE- is part of standard care), so the study authors are of the opinion that this additional precautionary measure does not itself increase the patient's risk or exposure to harm.

After the procedure, all participants (study or control) will have an endoscopy camera between 12-72 hours after the catheter ablation procedure to review for degree of oesophageal thermal damage caused by ablation, if any. (Please note: A biopsy is NOT part of this research protocol; this is simply a diagnostic camera.) The endoscopist is also blinded to the result of the randomization to avoid bias during reporting of the endoscopy result. The short time window between ablation and endoscopy camera follow up means that it can be done at the same admission as the ablation procedure itself, this is advantageous for the patient as both the ablation treatment and the follow up camera can be completed in 1 hospital admission. The endoscopy camera result is explained to the patient on the day and if any further action required. The timing is also advantageous to minimise separate hospital attendances in the Covid-19 era.

After this, normal/standard care clinic follow up of the patient will be adhered to but as part of the trial, at the first clinic follow up, participants in both groups will be asked about any lingering gastro-oesophageal symptoms and a record is made of this, for the study. The patient is still blinded to the results of the randomization at the time of reporting their symptoms during recovery, if any. This is to avoid bias/placebo effect.

The research project does not create any areas of ethical concern as the soft oesophageal cooling device/probe is of gentle design, specifically made to sit in the oesophagus. Especially when compared to the TOE probe that is normally used as part of standard protocol for an AF ablation procedure. The patient will also not be aware of this step at all as the procedure is conducted under general anaesthesia. The device is appropriately CE marked and used for the indication of body cooling via the oesophagus and protection. Even in standard care, an oesophageal temperature monitoring probe is required, so effectively, this study simply randomizes the patient to either the new probe or the standard of care one, during their AF ablation.

There is one additional follow up the participant is required to have, as part of this trial: the endoscopy camera (regardless of if randomised to study or control group). The endoscopy camera will be completed by 12-72hrs post catheter ablation procedure. The purpose is to review any areas of inflammation or thermal injury in the oesophagus that may alter clinical management but this specific information will also be used during study analysis of the 2 randomized groups after the study has completed. An endoscopy camera is considered to be a low risk day case procedure that takes 20 minutes to complete. The risk of this camera test causing any damage itself is <0.5%. A TOE probe/any other oesophageal probe used during the ablation procedure is similar to the endoscopy probe so apart from the participant having to attend an additional appointment after their ablation, the overall risk to the patient is not significantly increased.

The follow up endoscopy camera may be slightly uncomfortable in the beginning but it is not painful, is straightforward and relatively quick- this will be explained in the beginning during the recruitment process so the potential participant has an accurate idea of what to expect from the endoscopy camera and if they are happy to be enrolled. There is added benefit to the patient from this follow up, as the endoscopy camera will confirm to the patient about any oesophageal injury from ablation and if any treatment is required. If no injury, this can help to reassure the patient before they go home. Lastly, the follow up clinics will be as normal for the participant, only that investigators will ask specifically for any ongoing gastrooesophageal symptoms as well. A record of this will be made.

The study authors reviewed the steps involved with this study design and conclude that no major ethical or legal issue has been identified. The summary of the steps involved here hopefully clarifies our viewpoint. From a management perspective, our centre is designed to conduct catheter ablation procedures for AF with general anaesthetic cover. The authors have experience and acquired the necessary equipment from the oesophageal cooling device company and have appropriate device management protocols and storage space in place. External funding for the project has been secured to cover for the additional cost of the oesophageal cooling devices. The endoscopy department at the centre is also equipped and supportive of this study and are able to conduct the additional follow up endoscopy tests post ablation. The team are already accustomed to endoscopy test requests from the department, due to strong clinical indication, post catheter ablation.

Lastly, the authors have conducted this proposed research trial at a single-site setting to great success and with excellent safety record with no probe-related trauma and the team did not encounter any new or unexpected issues or difficulties. The authors obtained good patient feedback from the single-centre study. This same trial will run at 5 sites across the UK with potential to further expand depending on statistical analysis.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Patrick Shanley, MS; Phone Number: (888) 534-4873; Email: pshanley@attune-medical.com
• Study Contact Backup: Name: Avis Williams, MSPH; Phone Number: (888) 534-4873; Email: awilliams@attune-medical.com

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B15 2WB
    • Not yet recruiting
    • The Queen Elizabeth Hospital
    • Contact: Manish Kalla, MRCP, DPhil; Phone Number: 070980612080; Email: manish.kalla@uhb.nhs.uk
  • London, United Kingdom, SW170QT
    • Recruiting
    • St.George's Hospital
    • Contact: Mark M Gallagher, MD; Phone Number: 3701 +442087253701; Email: mark_m_gallagher@hotmail.com
    • Sub-Investigator: Manav Sohal, PhD
    • Sub-Investigator: Abhay Bajpai, MD
    • Sub-Investigator: Zia Zuberi, PhD
    • Sub-Investigator: Anthony Li, MD
    • Sub-Investigator: Mark Norman, PhD
    • Sub-Investigator: Riyaz Kaba, MD
  • London, United Kingdom, SE1 7EH
    • Not yet recruiting
    • Guy's and St Thomas' NHS Foundation Trust
    • Contact: Jaswinder Gill, MD; Phone Number: 02071887188; Email: jaswinder.gill@gstt.nhs.uk
  • Uxbridge, United Kingdom, UB9 6JH
    • Not yet recruiting
    • Royal Brompton & Harefield NHS Foundation Trust
    • Contact: Zhong Chen, MRCP, PhD; Phone Number: 070980612080; Email: z.chen@rbht.nhs.uk
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Not yet recruiting
      • University of Colorado
      • Principal Investigator: Wendy Tzou, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Not yet recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Jenifer Kaufman, RN, MS; Email: jmkaufma@bidmc.harvard.edu
      • Principal Investigator: Andrew Locke, MD
      • Principal Investigator: Timothy Maher, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Tiffany Sharksoski, BA; Phone Number: 215-615-2354; Email: Tiffany.Sharkoski@pennmedicine.upenn.edu
      • Principal Investigator: David Callans, MD
      • Principal Investigator: Cory Tscahbrunn, PhD
  • Texas
    • Austin, Texas, United States, 78705
      • Recruiting
      • Texas Cardiac Arrhythmia Research Foundation
      • Principal Investigator: Andrea Natale, MD
      • Contact: Deb Cardinal, RN; Phone Number: 512-431-4868
  • Virginia
    • Richmond, Virginia, United States, 23284
      • Not yet recruiting
      • Virginia Commonwealth University
      • Contact: Melissa Sears, MSN, CCRP; Phone Number: 804-628-1601; Email: melissa.sears@vcuhealth.org
      • Principal Investigator: Kenneth Ellenbogen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All AF patients deemed suitable for AF ablation treatment (under general anaesthetic) as per international guidelines and the patient has already decided on AF ablation treatment and are waiting for this procedure.

Exclusion Criteria:

• Inability to consent for any reason.
• Inability to have the endoscopy follow up for any reason.
• Those in extremities of age (<18 or >85) will not be recruited.
• Those with a history of upper gastrointestinal tract bleeding or at risk of trauma e.g. esophageal varices or stricture which means there is a contraindication for instrumentation of the esophagus for any reason during the ablation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Study group; Those randomized to the study group will receive the esophageal cooling device- the ensoETM probe, during AF ablation treatment, under general anaesthetic. The cooling device is set to 4 degrees covering ablation of the left atrial posterior wall.	Device: ensoETM. Esophageal cooling during AF ablation; Esophageal cooling during AF ablation: The ensoETM probe is inserted via the orogastric route when the patient is under general anaesthesia. The device is set to cool during ablation of the posterior aspect of the left atrium, to protect against transmitted thermal energy and so reduce or prevent esophageal thermal injury.
Active Comparator: Control group; Those randomized to the control group will receive standard of care, which is an esophageal temperature monitoring probe during their AF ablation procedure, under general anaesthetic. The esophageal temperature probe is sited close to the level of ablation (the probe should be at the esophageal level where, opposite this, the ablation catheter is at, in the endocardial aspect of the posterior left atrium).	Device: Esophageal temperature monitoring probe; An esophageal temperature monitoring probe is normally used in standard of care AF ablations. This allows any temperature rise in the esophagus to be detected during ablation. If the temperature reaches >38 degrees then it is widely recognised that ablation should be halted until the temperatures fall back to below 38 degrees. It therefore has the ability to detect esophageal temperature rise only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of endoscopically detected oesophageal thermal injury related to AF ablation. (Endoscopy at times 12-72 hours).	An upper gastrointestinal endoscopy diagnostic camera is performed under local anaesthetic spray and sedation. This is to screen for ablation-related thermal injury, which is highly characteristic and separate from other pathologies. This is performed for ALL participants of the trial regardless of randomization to study or control group.	Performed once, at 12-72 hours post ablation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedure duration (minutes).	A measure for procedure efficiency	Measured once. At time of AF ablation procedure (day 0)
Fluoroscopy duration (minutes)	A measure for procedure efficiency	Measured once. At time of AF ablation procedure (day 0)
Incidence of major adverse events (MACCE) at times 0, 3, 6, 12 months.	A measure of safety of AF ablation across both randomized groups.	Measured 4 times, at times: 0, 3, 6, 12 months from time of ablation.
Ability to attain procedural endpoints during AF ablation.	A measure of efficacy and efficiency of the AF ablation procedure: Attainment of ablation targets, including isolation of all veins and production of proven bidirectional block across all lines attempted.; Attainment of first-pass isolation for each set of veins; Persistence of isolation through waiting period and adenosine test (if used at operator's discretion).	Measured once at time points: time of AF ablation procedure (day 0).
Incidence of clinically significant chest/gastroenterological symptoms post ablation	Incidence of severe gastroenterological symptoms, indicative of oesophageal reflux or gastroparesis, from validated questionnaires (gastro-esophageal reflux disease score (GERDQ) and gastroparesis cardinal symptoms index (GCSI) score) administered >3 months from time of ablation.	Measured once at time points: 3 months from AF ablation procedure
Recurrence of treated atrial arrhythmia (AF or related AT)	Record any evidence of return of the treated arrhythmia at follow up cardiac monitoring: includes, 12 lead ECG, Holter, implantable loop recorders, non-invasive ECG monitors, mobile ECG apps. A return of AF (treated arrhythmia) must satisfy clear ECG/monitoring evidence of AF/related AT for >30 seconds. This is a measure of the success of the AF ablation procedure.	Measured at these time points: 3, 6, 12, 24 months from time of ablation procedure.

Collaborators and Investigators

• Sponsor: Advanced Cooling Therapy, Inc., d/b/a Attune Medical
• Collaborators: University of Colorado, Denver; University of Pennsylvania; Beth Israel Deaconess Medical Center; Guy's and St Thomas' NHS Foundation Trust; Virginia Commonwealth University; Royal Brompton & Harefield NHS Foundation Trust; National Health Service, United Kingdom; Berry Consultants; The Queen Elizabeth Hospital; St. George's Hospital, London; Texas Cardiac Arrhythmia Research Foundation
• Investigators: Principal Investigator: Mark M Gallagher, MD, St. George's NHS Trust; Principal Investigator: David Callans, MD, University of Pennsylvania

Publications and helpful links

General Publications

• Leung LW, Gallagher MM, Santangeli P, Tschabrunn C, Guerra JM, Campos B, Hayat J, Atem F, Mickelsen S, Kulstad E. Esophageal cooling for protection during left atrial ablation: a systematic review and meta-analysis. J Interv Card Electrophysiol. 2020 Nov;59(2):347-355. doi: 10.1007/s10840-019-00661-5. Epub 2019 Nov 22.
• Leung LW, Gallagher MM. Esophageal cooling for protection: an innovative tool that improves the safety of atrial fibrillation ablation. Expert Rev Med Devices. 2020 Oct;17(10):981-982. doi: 10.1080/17434440.2020.1824674. Epub 2020 Sep 21.
• Leung LWM, Gallagher MM. Letter in reply to Gianni et al on "Prevention, diagnosis, and management of atrioesophageal fistula". Pacing Clin Electrophysiol. 2020 Nov;43(11):1417-1418. doi: 10.1111/pace.14012. Epub 2020 Sep 3. No abstract available.
• Zagrodzky J, Gallagher MM, Leung LWM, Sharkoski T, Santangeli P, Tschabrunn C, Guerra JM, Campos B, MacGregor J, Hayat J, Clark B, Mazur A, Feher M, Arnold M, Metzl M, Nazari J, Kulstad E. Cooling or Warming the Esophagus to Reduce Esophageal Injury During Left Atrial Ablation in the Treatment of Atrial Fibrillation. J Vis Exp. 2020 Mar 15;(157). doi: 10.3791/60733.

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2022
• Primary Completion (Anticipated): March 10, 2024
• Study Completion (Anticipated): March 10, 2025

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: September 30, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): May 18, 2023
• Last Update Submitted That Met QC Criteria: May 17, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Esophageal protection; Radiofrequency; AF ablation; Esophageal thermal injury; atrio-esophageal fistula; Esophageal cooling; Esophageal temperature monitoring probe
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Gastrointestinal Diseases; Pathological Conditions, Anatomical; Arrhythmias, Cardiac; Esophageal Diseases; Digestive System Fistula; Atrial Fibrillation; Fistula; Esophageal Fistula
• Other Study ID Numbers: IRAS ID: 290265

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Anonymised study data will be shared with sponsor PI, CI and appointed medical scientists. Dataset will also be available for independent review by study monitors from the appointed CRO. Dataset will also be verified again by all site PIs.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes