Ignite Creation Date:
2024-05-06 @ 5:27 PM
Last Modification Date:
2024-10-26 @ 2:29 PM
Study NCT ID:
NCT05316753
Status:
UNKNOWN
Last Update Posted:
2022-07-25
First Post:
2022-03-08
Brief Title:
BTE and Pulsed Waveforms for Cardioversion of Atrial Fibrillation - Escalation Strategy and Manual Pressure
Sponsor:
University National Heart Hospital
Organization:
University National Heart Hospital
Study Overview
Official Title:
Comparison of Biphasic Truncated Exponential and Pulsed Waveforms for Cardioversion of Atrial Fibrillation-High Energy Escalation Strategy and Introduction to Manual Pressure Application
Status:
UNKNOWN
Status Verified Date:
2022-07
Last Known Status:
RECRUITING
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:
None
Brief Summary:
Background A Danish study raised the question of the usefulness of escalating energy protocols compared to fixed high-energy protocols Maximal energies are usually the final choice of the physicians Some authors showed that decreasing impedance by manual pressure application MPA had a positive impact on cardioversion outcome This is likely due to the impedance decrease linked to MPA
Objective This new clinical cardioversion study of atrial fibrillation AF patients aims to compare the efficacy and safety of a new high energy escalation strategy The protocol combines high energy shocks at first shock jumping to maximal defibrillator energy at second shock and finally complemented by MPA at third shock if success is not reached using electric shocks only
Experimental design Patients will be recruited at the Intensive Cardiology Care Unit Cardiology Clinic National Cardiology Hospital NCH Sofia Bulgaria All eligible patients will sign a written informed consent prior to the cardioversion and will receive the standard hospital procedures during cardioversion
AF patients will be alternatively randomized to cardioversion using one of the two defibrillators following the strategy below
DEFIGARD HD-7 arm 3 consecutive shocks with escalating selected energy 150J 200J 200J The third shock is combined with MPA LIFEPAK15 arm 3 consecutive shocks with escalating selected energy 150J 360J 360J The third shock is combined with MPA The statistical power analysis will consider a superiority comparison between the cumulative energy actually delivered by both defibrillators
The secondary cardioversion efficacy outcome measures are the cumulative success rate measured at 1 minute post-shock number of delivered shocks Delivered energy will be measured during each shock with a dedicated pulse recording device approved by the NCH Ethical Committee Heart rhythm will be measured in continuously recorded peripheral ECG
The secondary cardioversion safety outcome measures are markers for myocardial necrosis high sensitive troponin I CK-MB evaluated on blood samples taken before and 8-12 hours after cardioversion ST-segment changes post-shock - pre-shock measured in lead II Complications after cardioversion measured during 2 hours follow-up period in the ICCU - the presence of apnea arrhythmias bradycardia and the need for respective therapy at the discretion of attending physician
Objective This new clinical cardioversion study of atrial fibrillation AF patients aims to compare the efficacy and safety of a new high energy escalation strategy The protocol combines high energy shocks at first shock jumping to maximal defibrillator energy at second shock and finally complemented by MPA at third shock if success is not reached using electric shocks only
Experimental design Patients will be recruited at the Intensive Cardiology Care Unit Cardiology Clinic National Cardiology Hospital NCH Sofia Bulgaria All eligible patients will sign a written informed consent prior to the cardioversion and will receive the standard hospital procedures during cardioversion
AF patients will be alternatively randomized to cardioversion using one of the two defibrillators following the strategy below
DEFIGARD HD-7 arm 3 consecutive shocks with escalating selected energy 150J 200J 200J The third shock is combined with MPA LIFEPAK15 arm 3 consecutive shocks with escalating selected energy 150J 360J 360J The third shock is combined with MPA The statistical power analysis will consider a superiority comparison between the cumulative energy actually delivered by both defibrillators
The secondary cardioversion efficacy outcome measures are the cumulative success rate measured at 1 minute post-shock number of delivered shocks Delivered energy will be measured during each shock with a dedicated pulse recording device approved by the NCH Ethical Committee Heart rhythm will be measured in continuously recorded peripheral ECG
The secondary cardioversion safety outcome measures are markers for myocardial necrosis high sensitive troponin I CK-MB evaluated on blood samples taken before and 8-12 hours after cardioversion ST-segment changes post-shock - pre-shock measured in lead II Complications after cardioversion measured during 2 hours follow-up period in the ICCU - the presence of apnea arrhythmias bradycardia and the need for respective therapy at the discretion of attending physician
Detailed Description:
Background Commercially available defibrillators generate direct current DC shock with various waveforms using distinct technologies These waveforms are suggested to have different efficacy and safety Although the superiority of biphasic over monophasic waveforms is well established the relative efficacy and safety of the available biphasic waveforms is not clear
Various BTE waveforms apply different potential gradients on the thorax that might produce various defibrillation effects Apart from efficacy the most important aspect is the patient safety considering that larger potential gradients in the myocardium lasting longer could potentially induce an electroporation and then a fibrillation A frequently observed effect of electroporation are the post-shock ST-segment deviations in the surface ECG representing the potential difference between the normal tissue and sustained depolarized critical mass of myocardium closest to the associated origin of the electrical current Although ST-segment changes are an easily ignored phenomenon occurring acutely and resolving during the first few minutes post-shock their presence in a short-term basis can identify electroporation by dangerously high potential gradients while the sustained ST-changes in a long-term basis can identify cases with myocardial injury The most reliable marker of shock-induced myocardial injuries is the high sensitive cardiac Troponin I hsTnI
In a previous study Trendafilova et al were compared fixed-high energy protocols 200J-200J-200J delivered by two different defibrillation waveforms Pulsed BTE-PE and High-energy BTE BTE-HE This study concluded on non-inferiority between devices Cumulative energy efficiency of the waveforms and safety measured by High-sensitive Troponin were not reaching significant difference for both waveforms Delivered energy of the first efficient shock was significantly lower for BTE-PE and although BTE-PE delivered almost 28J lower energy after the whole procedure significance could not be reached due to wide variance
In a Danish study Schmidt et al compared two cardioversion protocols - one is fixed-high energy 360J-360J-360J the other is low energy escalating 125J-150J-200J The overall efficacy of fixed-energy protocol was better than escalating Safety is non significantly different Schmidt et al raised the question of the usefulness of escalating energy protocols compared to fixed high-energy protocols
There is an ethical consideration to apply maximal energy shocks to all patients without considering patient individuality Ramirez et al remind that failed shocks might depend on other factors like transthoracic impedance Lavignasse et al found that cumulative energy setting differs with patient characteristics having significant association with AF duration gender BSA LV TDD valvular disease and chronic respiratory disease Indeed some authors Voskoboinik et al and Ramirez et al showed that decreasing impedance by manual pressure application MPA had a positive impact on cardioversion outcome
On most defibrillators increasing the energy level is leading to an increase of the voltage delivered to the patient This voltage increase implies a current increase in the thorax of the patient In fact applying a force on the defibrillation pads or increasing shock voltage by increasing the energy setting would lead to increase the current in the thorax associated with expectations for higher shock efficiency MPA is performed by pressing on the pads using a non-connected pair of paddles in order to assure isolation of the practitioner from the patient during the shock
Objective
This new clinical cardioversion study of atrial fibrillation AF patients aims to compare the efficacy and safety of a new high energy escalation strategy The protocol combines reasonably high energy shocks complemented by MPA when necessary
Two biphasic defibrillators - a standard BTE-HE waveform Lifepak 15 Physio Control and a BTE-PE waveform Defigard HD 7 Schiller Medical with different maximal energy settings of 360J and 200J respectively are compared
The proposed high energy escalation strategy is based on the hypothesis that most of the patients do not implicitly require the maximal levels of energy for cardioversion Thus patients who could be easily cardioverted are removed from the pool that would need a more aggressive treatment
Methods
Study population All patients admitted for elective cardioversion of atrial fibrillation in ICCU- NCH will be potentially eligible for the study Informed consent will be obtained from all eligible patients prior to cardioversion Patients declining to participate in the study will receive treatment according to the hospital protocol
Cardiologists will check the eligibility of each patient following the detailed list of inclusion and exclusion criteria based on the documented pre-treatment data
Additionally eligibility will be verified through pre-cardioversion medical exams blood test within 24 hours before cardioversion routine blood chemistry glucose creatinine eGFR K Na CK-MB high sensitive troponin I measurements on the day of cardioversion
Study design This will be a prospective randomized trial alternating design where eligible patients will be randomized to treatment with two different defibrillators Following the order of patient admittance in ICCU-NCH the attending cardiologist will assign the odd and even eligible patients to the defibrillators in arm 1 and arm 2 respectively The cardiologist cannot control the order of patient admittance in ICCU-NCH The alternative randomization design will equalize the number of subjects on each treatment This study is not designed to control for sex age comorbidity type of device used for cardioversion cumulative energy delivered during shocks number of shocks administered Randomization is performed to limit these and any other confounding factors
Patient preparation Patients will be consulted prior to cardioversion CV in a quiet setting Any questions will be answered by the attending cardiologist Patients will be asked to manually sign their informed consent for study participation before further preparations and data collection If the patient declines to participate then heshe will receive treatment according to the hospital protocol without data documentation as further defined in the study
Demographic data will be taken Pre-treatment data will be read from the patient files concomitant diseases medications during the previous 7 days Left atrium dimensions left ventricle dimensions and volumes ejection fraction by transthoracic echocardiography during index hospitalization TEE will be performed for all patients before CV - presence of cardiac thrombus and spontaneous echo contrast will be checked duration of index AF in days European Heart Rhythm Association class score of symptoms from index AF standard blood test will be documented
Appropriate standard anticoagulation with unfractionated heparin UFH or acenocumarol or direct oral anticoagulants DOAC is required before and after the CV
The anesthesia will be conducted by an anesthesiologist with slow intravenous injection of Propofol adjusted individually to reach deep sedation Cook s scale points 7
Cardioversion protocol
The CV procedure is performed in ICCU by a cardiologist and anesthesiologist Defibrillator pads are placed according to the user guides on the pads and respecting 40 cm distance between them Standard self-adhesive defibrillation pads recommended by specific defibrillators manufacturer will be used
Defibrillator use The time-interval interval between consecutive shocks is 1 min The energy of consecutive shocks follows pre-defined protocol The protocol stops at successful cardioversion sinus rhythm at 1 min post-shock otherwise at the last shock of the protocol
Data collection and Follow up
Defibrillator pulse recorder The shock waveforms delivered by the studied defibrillators is recorded in real-time during the shock by a dedicated measurement device Defimpulse recorder DR2 connected in the patient circuit This allows accurate measurement of the delivered energy which is the primary measured outcome Additionally currents voltages patient impedances at each shock can be also measured The device is fully automatic and expert assistance is not need during the CV intervention The use of the measurement device Defimpulse recorder DR2 has been approved by the NCH Ethical Committee
Blood samples standard ECG blood pressure and heart rate at baseline
Continuous ECG in 3 peripheral leads is recorded during the whole CV procedure ST deviation is measured on the first cardiac complex after 10 s post-shock in standard manner 0080 seconds after J point in lead II
Standard ECG is recorded in 5 min after CV 24 h after CV at discharge if the discharge day is different from 24 h after CV
Heart rate and blood pressure are measured 3 times after CV during follow-up in ICCU
Follow-up period in ICCU 2 hours after CV Potential complications after CV are recorded
Follow-up period in the Cardiology Clinic 24 hours after CV blood samples to analyze CK-MB and troponin 8 to 12 h after CV Clinical exam with heart rate and blood pressure ECG Any complications before discharge
Statistics
For arm1 BTE PE waveform the expected efficacy is 50 at the first shock 150J 80 at the second shock 200J and 85 at the third shock 200J combined with MPA
For arm2 BTE HE waveform the expected efficacy is 50 at the first shock 150J 80 at the second shock 360J and 85 at the third shock 360J combined with MPA
Taking into account that BTE PE waveform typically delivers 180J for energy setting of 200J the estimated cumulative energy at the end of the CV procedure is 258J -120J and 366J -240J for arm1 and arm2 respectively
The statistical analysis is designed for a superiority comparison between the two defibrillation strategies in respect of their delivered cumulative energies hypothesizing similar cardioversion efficacy rate It is estimated that a total of 94 patients 47 per arm would allow to reach a statistical power of 80 in a superiority study design with one-sided type I error rate of 005
Continuous variables will be expressed as mean value standard deviation or median values inter-quartile range and compared with Students t-test or equivalent non-parametric test respectively Categorical variables are expressed as percentages and compared using the Chi-square or Fishers exact test P005 is considered statistically significant for all comparisons
Ethics All patients will sign a written informed consent prior to the cardioversion and will receive the standard hospital procedures during cardioversion Both defibrillators included in this study are approved for clinical use and both are used on a daily basis
Data anonymization policy will be respected In order to ensure the medical confidentiality no information about the patient will be entered in the defibrillators An identification number will be given to each patient by the dedicated measurement device Defimpulse recorder DR2 This number and the recording data are properties of the principal investigator Approval from the NCH Ethical Committee concerning energy strategy and the use of the Defimpulse recorder during the cardioversion intervention has been obtained
Various BTE waveforms apply different potential gradients on the thorax that might produce various defibrillation effects Apart from efficacy the most important aspect is the patient safety considering that larger potential gradients in the myocardium lasting longer could potentially induce an electroporation and then a fibrillation A frequently observed effect of electroporation are the post-shock ST-segment deviations in the surface ECG representing the potential difference between the normal tissue and sustained depolarized critical mass of myocardium closest to the associated origin of the electrical current Although ST-segment changes are an easily ignored phenomenon occurring acutely and resolving during the first few minutes post-shock their presence in a short-term basis can identify electroporation by dangerously high potential gradients while the sustained ST-changes in a long-term basis can identify cases with myocardial injury The most reliable marker of shock-induced myocardial injuries is the high sensitive cardiac Troponin I hsTnI
In a previous study Trendafilova et al were compared fixed-high energy protocols 200J-200J-200J delivered by two different defibrillation waveforms Pulsed BTE-PE and High-energy BTE BTE-HE This study concluded on non-inferiority between devices Cumulative energy efficiency of the waveforms and safety measured by High-sensitive Troponin were not reaching significant difference for both waveforms Delivered energy of the first efficient shock was significantly lower for BTE-PE and although BTE-PE delivered almost 28J lower energy after the whole procedure significance could not be reached due to wide variance
In a Danish study Schmidt et al compared two cardioversion protocols - one is fixed-high energy 360J-360J-360J the other is low energy escalating 125J-150J-200J The overall efficacy of fixed-energy protocol was better than escalating Safety is non significantly different Schmidt et al raised the question of the usefulness of escalating energy protocols compared to fixed high-energy protocols
There is an ethical consideration to apply maximal energy shocks to all patients without considering patient individuality Ramirez et al remind that failed shocks might depend on other factors like transthoracic impedance Lavignasse et al found that cumulative energy setting differs with patient characteristics having significant association with AF duration gender BSA LV TDD valvular disease and chronic respiratory disease Indeed some authors Voskoboinik et al and Ramirez et al showed that decreasing impedance by manual pressure application MPA had a positive impact on cardioversion outcome
On most defibrillators increasing the energy level is leading to an increase of the voltage delivered to the patient This voltage increase implies a current increase in the thorax of the patient In fact applying a force on the defibrillation pads or increasing shock voltage by increasing the energy setting would lead to increase the current in the thorax associated with expectations for higher shock efficiency MPA is performed by pressing on the pads using a non-connected pair of paddles in order to assure isolation of the practitioner from the patient during the shock
Objective
This new clinical cardioversion study of atrial fibrillation AF patients aims to compare the efficacy and safety of a new high energy escalation strategy The protocol combines reasonably high energy shocks complemented by MPA when necessary
Two biphasic defibrillators - a standard BTE-HE waveform Lifepak 15 Physio Control and a BTE-PE waveform Defigard HD 7 Schiller Medical with different maximal energy settings of 360J and 200J respectively are compared
The proposed high energy escalation strategy is based on the hypothesis that most of the patients do not implicitly require the maximal levels of energy for cardioversion Thus patients who could be easily cardioverted are removed from the pool that would need a more aggressive treatment
Methods
Study population All patients admitted for elective cardioversion of atrial fibrillation in ICCU- NCH will be potentially eligible for the study Informed consent will be obtained from all eligible patients prior to cardioversion Patients declining to participate in the study will receive treatment according to the hospital protocol
Cardiologists will check the eligibility of each patient following the detailed list of inclusion and exclusion criteria based on the documented pre-treatment data
Additionally eligibility will be verified through pre-cardioversion medical exams blood test within 24 hours before cardioversion routine blood chemistry glucose creatinine eGFR K Na CK-MB high sensitive troponin I measurements on the day of cardioversion
Study design This will be a prospective randomized trial alternating design where eligible patients will be randomized to treatment with two different defibrillators Following the order of patient admittance in ICCU-NCH the attending cardiologist will assign the odd and even eligible patients to the defibrillators in arm 1 and arm 2 respectively The cardiologist cannot control the order of patient admittance in ICCU-NCH The alternative randomization design will equalize the number of subjects on each treatment This study is not designed to control for sex age comorbidity type of device used for cardioversion cumulative energy delivered during shocks number of shocks administered Randomization is performed to limit these and any other confounding factors
Patient preparation Patients will be consulted prior to cardioversion CV in a quiet setting Any questions will be answered by the attending cardiologist Patients will be asked to manually sign their informed consent for study participation before further preparations and data collection If the patient declines to participate then heshe will receive treatment according to the hospital protocol without data documentation as further defined in the study
Demographic data will be taken Pre-treatment data will be read from the patient files concomitant diseases medications during the previous 7 days Left atrium dimensions left ventricle dimensions and volumes ejection fraction by transthoracic echocardiography during index hospitalization TEE will be performed for all patients before CV - presence of cardiac thrombus and spontaneous echo contrast will be checked duration of index AF in days European Heart Rhythm Association class score of symptoms from index AF standard blood test will be documented
Appropriate standard anticoagulation with unfractionated heparin UFH or acenocumarol or direct oral anticoagulants DOAC is required before and after the CV
The anesthesia will be conducted by an anesthesiologist with slow intravenous injection of Propofol adjusted individually to reach deep sedation Cook s scale points 7
Cardioversion protocol
The CV procedure is performed in ICCU by a cardiologist and anesthesiologist Defibrillator pads are placed according to the user guides on the pads and respecting 40 cm distance between them Standard self-adhesive defibrillation pads recommended by specific defibrillators manufacturer will be used
Defibrillator use The time-interval interval between consecutive shocks is 1 min The energy of consecutive shocks follows pre-defined protocol The protocol stops at successful cardioversion sinus rhythm at 1 min post-shock otherwise at the last shock of the protocol
Data collection and Follow up
Defibrillator pulse recorder The shock waveforms delivered by the studied defibrillators is recorded in real-time during the shock by a dedicated measurement device Defimpulse recorder DR2 connected in the patient circuit This allows accurate measurement of the delivered energy which is the primary measured outcome Additionally currents voltages patient impedances at each shock can be also measured The device is fully automatic and expert assistance is not need during the CV intervention The use of the measurement device Defimpulse recorder DR2 has been approved by the NCH Ethical Committee
Blood samples standard ECG blood pressure and heart rate at baseline
Continuous ECG in 3 peripheral leads is recorded during the whole CV procedure ST deviation is measured on the first cardiac complex after 10 s post-shock in standard manner 0080 seconds after J point in lead II
Standard ECG is recorded in 5 min after CV 24 h after CV at discharge if the discharge day is different from 24 h after CV
Heart rate and blood pressure are measured 3 times after CV during follow-up in ICCU
Follow-up period in ICCU 2 hours after CV Potential complications after CV are recorded
Follow-up period in the Cardiology Clinic 24 hours after CV blood samples to analyze CK-MB and troponin 8 to 12 h after CV Clinical exam with heart rate and blood pressure ECG Any complications before discharge
Statistics
For arm1 BTE PE waveform the expected efficacy is 50 at the first shock 150J 80 at the second shock 200J and 85 at the third shock 200J combined with MPA
For arm2 BTE HE waveform the expected efficacy is 50 at the first shock 150J 80 at the second shock 360J and 85 at the third shock 360J combined with MPA
Taking into account that BTE PE waveform typically delivers 180J for energy setting of 200J the estimated cumulative energy at the end of the CV procedure is 258J -120J and 366J -240J for arm1 and arm2 respectively
The statistical analysis is designed for a superiority comparison between the two defibrillation strategies in respect of their delivered cumulative energies hypothesizing similar cardioversion efficacy rate It is estimated that a total of 94 patients 47 per arm would allow to reach a statistical power of 80 in a superiority study design with one-sided type I error rate of 005
Continuous variables will be expressed as mean value standard deviation or median values inter-quartile range and compared with Students t-test or equivalent non-parametric test respectively Categorical variables are expressed as percentages and compared using the Chi-square or Fishers exact test P005 is considered statistically significant for all comparisons
Ethics All patients will sign a written informed consent prior to the cardioversion and will receive the standard hospital procedures during cardioversion Both defibrillators included in this study are approved for clinical use and both are used on a daily basis
Data anonymization policy will be respected In order to ensure the medical confidentiality no information about the patient will be entered in the defibrillators An identification number will be given to each patient by the dedicated measurement device Defimpulse recorder DR2 This number and the recording data are properties of the principal investigator Approval from the NCH Ethical Committee concerning energy strategy and the use of the Defimpulse recorder during the cardioversion intervention has been obtained
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None