Ignite Creation Date:
2024-05-06 @ 1:44 PM
Last Modification Date:
2024-10-26 @ 1:18 PM
Study NCT ID:
NCT04101539
Status:
RECRUITING
Last Update Posted:
2023-09-26
First Post:
2019-09-23
Brief Title:
Comparing Pulmonary Vein Isolation to Pulmonary Vein Isolation OPTIMA Ablation in Patients Undergoing Ablation for Atrial Fibrillation
Sponsor:
Johns Hopkins University
Organization:
Johns Hopkins University
Study Overview
Official Title:
A Randomized Trial Comparing Pulmonary Vein Isolation to Pulmonary Vein Isolation OPTIMA Ablation in Patients Undergoing Ablation for Atrial Fibrillation
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
OPTIMA
Brief Summary:
Catheter ablation is an established cornerstone of therapy for patients with symptomatic atrial fibrillation AF who wish to avoid anti-arrhythmic drug therapy or for whom anti-arrhythmics have proven ineffective Pulmonary vein isolation PVI in which circumferential ablation is performed around the ostia of the pulmonary vein - left atrial junctions is the standard ablation approach internationally Single-procedure success rates 1y freedom from AF off anti-arrhythmics for patients with paroxysmal AF is roughly 70 and even worse roughly 50 for patients with persistent AF
A number of strategies have been developed to improve outcomes in patients undergoing AF ablation particularly in patients with persistent AF Unfortunately large prospective randomized trials including STAR-AF II published in NEJM in 2015 have demonstrated a failure of ancillary ablation techniques to improve AF ablation outcomes relative to PVI alone
In a collaborative effort between the Cardiology electrophysiology group and the Trayanova laboratory Biomechanical Engineering investigators have developed a strategy of patient-specific modeling to identify pro-arrhythmic sites in AF patients that may be amenable to ablation In this approach patients undergo a pre-ablation cardiac MRI with late gadolinium enhancement to delineate regions of healthy atrial tissue and regions of scar this scan is clinically indicated and performed currently in patients undergoing PVI for AF A novel in silico modeling to determine regions supporting electrical reentry in the atrium driving ongoing AF has been developed by the Trayanova lab In preliminary studies investigators have demonstrated the ability to identify and target these regions with catheter ablation in patients undergoing PVI
Investigators would like to conduct a prospective randomized clinical trial in patients undergoing ablation for symptomatic persistent AF All patients enrolled would undergo standard pre-procedure imaging LGE-MRI prior to the day of procedure Investigators have developed methodology termed OPTIMA OPtimal Target Identification via Modeling of Arrhythmogenesis to determine based on non-invasive patient-specific anatomic and tissue data from late gadolinium enhancement cardiac MRI LGE-CMR and simulation of cardiac electrical function personalized ablation targets for persistent AF in patients with fibrotic remodeling Patients would be randomized to receiving PVI only versus PVI OPTIMA ablation at the time of ablation Patients would then be followed in standard clinical fashion at 3m 6m and 12m to assess for ablation efficacy and for procedural complications
Investigators postulate a 20 improvement in freedom from AF with PVI OPTIMA ablation form 50 to 70 compared to PVI alone investigators anticipate that in 11 randomization a sample size of 80 patients in each arm will yield a power calculation of 80 with an alpha of 005 Investigators anticipate that enrollment and 1y clinical follow-up for 160 patients total undergoing AF ablation will require a 4y timeline
A number of strategies have been developed to improve outcomes in patients undergoing AF ablation particularly in patients with persistent AF Unfortunately large prospective randomized trials including STAR-AF II published in NEJM in 2015 have demonstrated a failure of ancillary ablation techniques to improve AF ablation outcomes relative to PVI alone
In a collaborative effort between the Cardiology electrophysiology group and the Trayanova laboratory Biomechanical Engineering investigators have developed a strategy of patient-specific modeling to identify pro-arrhythmic sites in AF patients that may be amenable to ablation In this approach patients undergo a pre-ablation cardiac MRI with late gadolinium enhancement to delineate regions of healthy atrial tissue and regions of scar this scan is clinically indicated and performed currently in patients undergoing PVI for AF A novel in silico modeling to determine regions supporting electrical reentry in the atrium driving ongoing AF has been developed by the Trayanova lab In preliminary studies investigators have demonstrated the ability to identify and target these regions with catheter ablation in patients undergoing PVI
Investigators would like to conduct a prospective randomized clinical trial in patients undergoing ablation for symptomatic persistent AF All patients enrolled would undergo standard pre-procedure imaging LGE-MRI prior to the day of procedure Investigators have developed methodology termed OPTIMA OPtimal Target Identification via Modeling of Arrhythmogenesis to determine based on non-invasive patient-specific anatomic and tissue data from late gadolinium enhancement cardiac MRI LGE-CMR and simulation of cardiac electrical function personalized ablation targets for persistent AF in patients with fibrotic remodeling Patients would be randomized to receiving PVI only versus PVI OPTIMA ablation at the time of ablation Patients would then be followed in standard clinical fashion at 3m 6m and 12m to assess for ablation efficacy and for procedural complications
Investigators postulate a 20 improvement in freedom from AF with PVI OPTIMA ablation form 50 to 70 compared to PVI alone investigators anticipate that in 11 randomization a sample size of 80 patients in each arm will yield a power calculation of 80 with an alpha of 005 Investigators anticipate that enrollment and 1y clinical follow-up for 160 patients total undergoing AF ablation will require a 4y timeline
Detailed Description:
Background Atrial fibrillation AF is the most commonly encountered clinical arrhythmia Symptoms arising from AF are common and may include palpitations fatigue exertional intolerance and angina Relief of symptoms is achieved by rhythm control strategies including drug therapy and catheter ablation for AF Catheter ablation is more effective than drug therapy is the preferred method of rhythm control for patients in whom drug therapy has been ineffective or intolerable and is increasingly used as first-line therapy However success rates for AF control after catheter ablation are imperfect with AF recurrence rates between 30 - 50 at 1 year Currently catheter ablation focuses almost exclusively on electrical isolation of the pulmonary vein PV ostia PV isolation PVI to eliminate triggering activity from ectopic foci in the PVs that in the vast majority of patients initiate AF A number of strategies have been developed to improve outcomes in patients undergoing AF ablation particularly in patients with persistent AF Unfortunately large prospective randomized trials including STAR-AF II NEJM 2015 have demonstrated a failure of ancillary ablation techniques to improve AF ablation outcomes relative to PVI alone The failure of PVI and ancillary ablation techniques to deliver reasonable outcomes is exacerbated in patients with persistent AF PsAF who develop fibrosis in the atria These patients have AF ablation outcomes that are demonstrably worse than those seen in patients with persistent AF Investigators have recently developed methodology termed OPTIMA OPtimal Target Identification via Modeling of Arrhythmogenesis to determine based on non-invasive patient-specific anatomic and tissue data from late gadolinium enhancement cardiac MRI LGE-CMR and simulation of cardiac electrical function personalized ablation targets for persistent AF in patients with fibrotic remodeling These targets which are determined off line pre-procedure are then used to steer patient treatment This technology is intended to make the procedure accurate and efficacious in persistent AF patients with fibrosis and to eliminate the need for repeat ablations offering long-term freedom from AF
Hypothesis In patients undergoing ablation for the treatment of persistent AF using the OPTIMA approach and performing PV isolation during ablation for AF will improve outcomes compared to performing PV isolation alone
Importance In United States Center for disease control estimates that 27-61 million people suffer with AF and expects this number to increase with the aging population Ablation for AF is performed at increasing rates and in certain population eg patients with paroxysmal AF is moderately effective Even in optimal patients however the rate of AF recurrence following apparently successful PV isolation is high 2017 Heart Rhythm Society HRS Consensus statement on AF ablation Strategies to improve AF ablation outcomes should result in improved patient health symptom elimination lower patient risk reduction of the number of patients undergoing redo ablation procedures and reduced economic burden from healthcare costs reducing post-ablation treatment for AF including redo ablation procedures Furthermore demonstration of the arrhythmogenic propensity of fibrotic remodeling in patients with persistent AF will add to investigators collective understanding of the fundamental mechanisms underlying AF initiation and perpetuation
Objectives The goal of this study is to test the efficacy of the OPTIMA approach for determining the optimal ablation targets in patients with persistent AF and fibrosis and to demonstrate that elimination of AF-perpetuating sources in the fibrotic substrate in conjunction with PVI during AF ablation improves rate of AF-free survival at 1 year compared to patients undergoing standard PVI alone
Study Procedures
This study is a prospective randomized single-blind study of patients undergoing either standard PV isolation or PVIOPTIMA ablation for the treatment of symptomatic persistent AF Patients referred for ablation for symptomatic persistent AF will be considered for enrollment Patients will have cardiac function and anatomy assessed by echocardiography in the six-month window prior to ablation routine care Patients will have a baseline rhythm assessment with Ziopatch to quantify pre-ablation AF burden All patients will undergo pre-procedure LGE-CMR to delineate atrial anatomy routine care MRI scan will be obtained in sinus rhythm patients will be cardiovertered before MRI if the patients are in atrial fibrillation All patients will be anticoagulated according to standard clinical guidelines Patients with a CHADS VASc score of 2 or greater will be systemically anticoagulated in the pre- peri- and post-procedural periods Patients not otherwise requiring long-term systemic anticoagulation will be anticoagulated during the peri- and post-procedural intervals minimum of 2 months systemic anticoagulation following ablation Finally any patient undergoing cardioversion to facilitate MRI acquisition will receive systemic anticoagulation for a minimum of three weeks prior to cardioversion andor have a Transesophageal Echocardiography TEE performed prior to cardioversion After CMR acquisition patients will be randomized to PVI versus PVIOPTIMA ablation Pre-procedural TEE is not required for patients presenting in Sinus rhythm and on uninterrupted anticoagulation for at least 3 weeks regardless of CHADS VASC score Patients presenting either in atrial fibrillation or not on uninterrupted anticoagulation will undergo a pre-procedural TEE again independent of CHADS VASC score All patients will undergo AF ablation with PVI routine care At the outset of the procedure electroanatomical mapping of the Left Atrium LA will be performed to facilitate clinical ablation with typically 1000 datapoints captured in the LA PVI will be performed in all patients In the PVIOPTIMA arm sites identified as targets by pre-procedure modeling will subsequently be targeted for ablation research procedure during routine ablation procedure Additional ablation of other atrial targets lines complex fractionated electrograms will be discouraged in both arms but ultimately targeting such areas will be left to the discretion of the operator In both arms PV isolation will be assessed by entrance block OPTIMA lesions will be assessed by both minimum of 50 percentage reduction in all local Electrograms EGM as well as non-capture by high output pacing at the site of target ablation Operator will have the discretion not to ablate certain OPTIMA targets for safety reasons including but not limited to avoid critical structures and patient hemodynamic status Operator will document the reason for not ablating all OPTIMA targets in the case report forms Patients will be maintained on anti-arrhythmic drugs during the healing phase 3m following ablation with medication changes cessation up-titration or drug changes made at the discretion of the treating physician All patients will be followed clinically after ablation in the standard fashion routine care including visits at 3 6 and 12 months with AF burden assessment with Zio patch at each visit
Study duration and number of study visits required of research participants
Investigators anticipate that this study will take 3 years for enrollment and 1 year clinical follow-up Patient encounters include a pre-procedure clinical assessment and rhythm assessmentzio patch in outpatient Electrophysiology EP Clinic cardiac MRI in the week prior to ablation the ablation procedure itself overnight monitoring in the hospital following ablation clinical assessment at 3 6 and 12 months after ablation including rhythm assessment with Ziopatch at each visit Additional rhythm assessment with Ziopatch will be performed for patients with clinical symptoms of atrial fibrillation Of note these encounters are all part of current clinical practice in patients undergoing AF ablation
Blinding including justification for blinding or not blinding the trial if applicable
Patients will be blinded to the ablation strategy PVI only versus PVIOPTIMA ablation Operators by necessity cannot be blinded to the ablation strategy as patients are performing the ablations
Risks
All patients in the study will undergo standard PVI with its attendant risks These risks include those related to general anesthesia risk of stroke risk of cardiac puncture risk of esophageal injury risk of other cardiac damage and risk related to vascular access Patients randomized to Re-entrant Driver RD ablation will undergo standard PVI with risks listed above During ablation operators will target additional sites for lesion delivery This is anticipated to lead to increases in procedure time left atrial dwell time number of lesions delivered and increased radiation exposure
Investigators anticipate that the additional risk to patients undergoing OPTIMA ablation in addition to PVI will be minimal Typical PVI involves lesion delivery at 50-60 sites In investigators early experience patients have between 2-5 AF sources in the fibrotic substrate that OPTIMA targets Thus the additional ablation in each patient is likely to be a small component of the total ablation lesion set additional risks are a function largely of time manipulating catheters and ablating in the left atrium This added time will be minimal
Radiation exposure Patients undergoing standard ablation procedure is estimated to be estimated to have 0700 rems of radiation exposure due to fluoroscopy Patients undergoing optima ablation are estimated to be exposed to additional 014 rems of radiation
Risks of ECG patch monitor Clinical trials have so far shown the Zio XT is well-tolerated in the overall population The risks associated with Zio patch include mild discomfort andor allergic reaction to sticky pads used to attach the Zio patch
There is a possibility that while reviewing ones patch monitor results investigators may detect a heart rhythm abnormality that investigators did not expect to find Investigators will contact the patient and inform the patient and hisher clinical cardiac electrophysiologist regarding the result The costs for any care that may arise in reaction to this incidental finding will not be covered by this research study
Steps taken to minimize the risks
Currently investigators employ a number of risk mitigation strategies including the use of electroanatomical mapping systems to minimize radiation exposure the use of systemic anticoagulation to minimize Cardiovascular Accident CVA risk the use of ultrasound guided vascular access to minimize vascular complication rates All of these strategies will be employed for all study participants In addition following monitoring procedures will be followed during the study
Data quality will be monitored routinely and reviewed monthly for missing data inconsistent data data outliers and potential protocol deviations
All adverse events and protocol deviations will be notified to PI
In order to minimize risks to patients enrolled in the study all adverse events will be discussed in the monthly cardiac electrophysiology complications conference This conference will serve as the Global safety monitoring committee
All Attending physicians participating in this study including David Spragg MD Ronal Berger MD Hugh Calkins MD Joseph Marine MD and Hiroshi Ashikaga MD PhD attend this conference
All adverse events will be assessed in terms of relationship to device relationship to procedure severity subsequent intervention required and resolution status
Benefits
Strategies to improve AF ablation outcomes should result in improved patient health symptom elimination lower patient risk reduction of the number of patients undergoing redo ablation procedures and reduced economic burden from healthcare costs reducing post-ablation treatment for AF including redo ablation procedures Furthermore demonstration of the importance of elimination of the arrhythmogenic propensity of the fibrotic substrate in patients with PsAF will add to investigators collective understanding of the fundamental mechanisms underlying AF initiation and perpetuation
Hypothesis In patients undergoing ablation for the treatment of persistent AF using the OPTIMA approach and performing PV isolation during ablation for AF will improve outcomes compared to performing PV isolation alone
Importance In United States Center for disease control estimates that 27-61 million people suffer with AF and expects this number to increase with the aging population Ablation for AF is performed at increasing rates and in certain population eg patients with paroxysmal AF is moderately effective Even in optimal patients however the rate of AF recurrence following apparently successful PV isolation is high 2017 Heart Rhythm Society HRS Consensus statement on AF ablation Strategies to improve AF ablation outcomes should result in improved patient health symptom elimination lower patient risk reduction of the number of patients undergoing redo ablation procedures and reduced economic burden from healthcare costs reducing post-ablation treatment for AF including redo ablation procedures Furthermore demonstration of the arrhythmogenic propensity of fibrotic remodeling in patients with persistent AF will add to investigators collective understanding of the fundamental mechanisms underlying AF initiation and perpetuation
Objectives The goal of this study is to test the efficacy of the OPTIMA approach for determining the optimal ablation targets in patients with persistent AF and fibrosis and to demonstrate that elimination of AF-perpetuating sources in the fibrotic substrate in conjunction with PVI during AF ablation improves rate of AF-free survival at 1 year compared to patients undergoing standard PVI alone
Study Procedures
This study is a prospective randomized single-blind study of patients undergoing either standard PV isolation or PVIOPTIMA ablation for the treatment of symptomatic persistent AF Patients referred for ablation for symptomatic persistent AF will be considered for enrollment Patients will have cardiac function and anatomy assessed by echocardiography in the six-month window prior to ablation routine care Patients will have a baseline rhythm assessment with Ziopatch to quantify pre-ablation AF burden All patients will undergo pre-procedure LGE-CMR to delineate atrial anatomy routine care MRI scan will be obtained in sinus rhythm patients will be cardiovertered before MRI if the patients are in atrial fibrillation All patients will be anticoagulated according to standard clinical guidelines Patients with a CHADS VASc score of 2 or greater will be systemically anticoagulated in the pre- peri- and post-procedural periods Patients not otherwise requiring long-term systemic anticoagulation will be anticoagulated during the peri- and post-procedural intervals minimum of 2 months systemic anticoagulation following ablation Finally any patient undergoing cardioversion to facilitate MRI acquisition will receive systemic anticoagulation for a minimum of three weeks prior to cardioversion andor have a Transesophageal Echocardiography TEE performed prior to cardioversion After CMR acquisition patients will be randomized to PVI versus PVIOPTIMA ablation Pre-procedural TEE is not required for patients presenting in Sinus rhythm and on uninterrupted anticoagulation for at least 3 weeks regardless of CHADS VASC score Patients presenting either in atrial fibrillation or not on uninterrupted anticoagulation will undergo a pre-procedural TEE again independent of CHADS VASC score All patients will undergo AF ablation with PVI routine care At the outset of the procedure electroanatomical mapping of the Left Atrium LA will be performed to facilitate clinical ablation with typically 1000 datapoints captured in the LA PVI will be performed in all patients In the PVIOPTIMA arm sites identified as targets by pre-procedure modeling will subsequently be targeted for ablation research procedure during routine ablation procedure Additional ablation of other atrial targets lines complex fractionated electrograms will be discouraged in both arms but ultimately targeting such areas will be left to the discretion of the operator In both arms PV isolation will be assessed by entrance block OPTIMA lesions will be assessed by both minimum of 50 percentage reduction in all local Electrograms EGM as well as non-capture by high output pacing at the site of target ablation Operator will have the discretion not to ablate certain OPTIMA targets for safety reasons including but not limited to avoid critical structures and patient hemodynamic status Operator will document the reason for not ablating all OPTIMA targets in the case report forms Patients will be maintained on anti-arrhythmic drugs during the healing phase 3m following ablation with medication changes cessation up-titration or drug changes made at the discretion of the treating physician All patients will be followed clinically after ablation in the standard fashion routine care including visits at 3 6 and 12 months with AF burden assessment with Zio patch at each visit
Study duration and number of study visits required of research participants
Investigators anticipate that this study will take 3 years for enrollment and 1 year clinical follow-up Patient encounters include a pre-procedure clinical assessment and rhythm assessmentzio patch in outpatient Electrophysiology EP Clinic cardiac MRI in the week prior to ablation the ablation procedure itself overnight monitoring in the hospital following ablation clinical assessment at 3 6 and 12 months after ablation including rhythm assessment with Ziopatch at each visit Additional rhythm assessment with Ziopatch will be performed for patients with clinical symptoms of atrial fibrillation Of note these encounters are all part of current clinical practice in patients undergoing AF ablation
Blinding including justification for blinding or not blinding the trial if applicable
Patients will be blinded to the ablation strategy PVI only versus PVIOPTIMA ablation Operators by necessity cannot be blinded to the ablation strategy as patients are performing the ablations
Risks
All patients in the study will undergo standard PVI with its attendant risks These risks include those related to general anesthesia risk of stroke risk of cardiac puncture risk of esophageal injury risk of other cardiac damage and risk related to vascular access Patients randomized to Re-entrant Driver RD ablation will undergo standard PVI with risks listed above During ablation operators will target additional sites for lesion delivery This is anticipated to lead to increases in procedure time left atrial dwell time number of lesions delivered and increased radiation exposure
Investigators anticipate that the additional risk to patients undergoing OPTIMA ablation in addition to PVI will be minimal Typical PVI involves lesion delivery at 50-60 sites In investigators early experience patients have between 2-5 AF sources in the fibrotic substrate that OPTIMA targets Thus the additional ablation in each patient is likely to be a small component of the total ablation lesion set additional risks are a function largely of time manipulating catheters and ablating in the left atrium This added time will be minimal
Radiation exposure Patients undergoing standard ablation procedure is estimated to be estimated to have 0700 rems of radiation exposure due to fluoroscopy Patients undergoing optima ablation are estimated to be exposed to additional 014 rems of radiation
Risks of ECG patch monitor Clinical trials have so far shown the Zio XT is well-tolerated in the overall population The risks associated with Zio patch include mild discomfort andor allergic reaction to sticky pads used to attach the Zio patch
There is a possibility that while reviewing ones patch monitor results investigators may detect a heart rhythm abnormality that investigators did not expect to find Investigators will contact the patient and inform the patient and hisher clinical cardiac electrophysiologist regarding the result The costs for any care that may arise in reaction to this incidental finding will not be covered by this research study
Steps taken to minimize the risks
Currently investigators employ a number of risk mitigation strategies including the use of electroanatomical mapping systems to minimize radiation exposure the use of systemic anticoagulation to minimize Cardiovascular Accident CVA risk the use of ultrasound guided vascular access to minimize vascular complication rates All of these strategies will be employed for all study participants In addition following monitoring procedures will be followed during the study
Data quality will be monitored routinely and reviewed monthly for missing data inconsistent data data outliers and potential protocol deviations
All adverse events and protocol deviations will be notified to PI
In order to minimize risks to patients enrolled in the study all adverse events will be discussed in the monthly cardiac electrophysiology complications conference This conference will serve as the Global safety monitoring committee
All Attending physicians participating in this study including David Spragg MD Ronal Berger MD Hugh Calkins MD Joseph Marine MD and Hiroshi Ashikaga MD PhD attend this conference
All adverse events will be assessed in terms of relationship to device relationship to procedure severity subsequent intervention required and resolution status
Benefits
Strategies to improve AF ablation outcomes should result in improved patient health symptom elimination lower patient risk reduction of the number of patients undergoing redo ablation procedures and reduced economic burden from healthcare costs reducing post-ablation treatment for AF including redo ablation procedures Furthermore demonstration of the importance of elimination of the arrhythmogenic propensity of the fibrotic substrate in patients with PsAF will add to investigators collective understanding of the fundamental mechanisms underlying AF initiation and perpetuation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None