Ignite Creation Date:
2024-05-06 @ 1:29 PM
Last Modification Date:
2024-10-26 @ 1:14 PM
Study NCT ID:
NCT04032678
Status:
COMPLETED
Last Update Posted:
2020-08-25
First Post:
2019-07-12
Brief Title:
Comparison of Efficacy and Safety of Two Biphasic Defibrillators in Cardioversion of Atrial Fibrillation
Sponsor:
University National Heart Hospital
Organization:
University National Heart Hospital
Study Overview
Official Title:
A Comparison of Biphasic Truncated Exponential and Pulsed Waveforms for Cardioversion of Atrial Fibrillation
Status:
COMPLETED
Status Verified Date:
2020-08
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:
None
Brief Summary:
Background Biphasic truncated exponential BTE waveforms are standard for cardiac defibrillation and synchronized cardioversion up to date BTE waveforms differ by design characteristics and technologies for pulse commutation rectilinear standard truncated exponential pulsed Clinical evaluation of BTE waveforms can be planned during cardioversion CVS as a well-established procedure of atrial fibrillation patients who are able to give consent and also present a more controlled population
Scarce studies have been found to present the relative efficacy and safety of different BTE waveforms during CVS The validity of significantly deviating results of the pulsed waveform in one CVS study is questionable
Objective To compare the CVS efficacy and safety two different biphasic defibrillators - a standard truncated exponential waveform and a pulsed biphasic waveform
Experimental design Patients will be recruited at the Intensive Cardiology Care Unit ICCU Cardiology Clinic University National Heart Hospital NHH Sofia Bulgaria underwent the pre-CVS medical exams and check for eligibility All eligible patients will sign a written informed consent prior to the CVS and will receive the standard hospital procedures during CVS accepted in the NHH and approved by the NHH Local Ethic Committee
Atrial fibrillation patients will be alternatively randomized to CVS using one of the two defibrillators following the same energy selection protocol in both defibrillators The statistical power analysis will consider a non-inferiority comparison between the cumulative energy actually delivered by both defibrillators
The secondary CVS outcome measures are the cumulative success rate measured at 1 minute post-shock and number of delivered shocks Delivered energy will be measured during each shock with a dedicated pulse recording device approved by the NHH Local Ethic Committee Heart rhythm will be monitoring in continuously recorded peripheral ECG
The secondary CVS safety outcome measures Biochemical markers for myocardial necrosis high sensitive troponin I - hsTnI creatine kinase MB fraction - CK-MB will be evaluated on blood samples taken before and 12 hours after cardioversion ST-segment changes will be measured in lead II baseline and 10 s post-shock and 12-lead ECG Complications after cardioversion will be measured during 2 hours follow-up period in the ICCU
Scarce studies have been found to present the relative efficacy and safety of different BTE waveforms during CVS The validity of significantly deviating results of the pulsed waveform in one CVS study is questionable
Objective To compare the CVS efficacy and safety two different biphasic defibrillators - a standard truncated exponential waveform and a pulsed biphasic waveform
Experimental design Patients will be recruited at the Intensive Cardiology Care Unit ICCU Cardiology Clinic University National Heart Hospital NHH Sofia Bulgaria underwent the pre-CVS medical exams and check for eligibility All eligible patients will sign a written informed consent prior to the CVS and will receive the standard hospital procedures during CVS accepted in the NHH and approved by the NHH Local Ethic Committee
Atrial fibrillation patients will be alternatively randomized to CVS using one of the two defibrillators following the same energy selection protocol in both defibrillators The statistical power analysis will consider a non-inferiority comparison between the cumulative energy actually delivered by both defibrillators
The secondary CVS outcome measures are the cumulative success rate measured at 1 minute post-shock and number of delivered shocks Delivered energy will be measured during each shock with a dedicated pulse recording device approved by the NHH Local Ethic Committee Heart rhythm will be monitoring in continuously recorded peripheral ECG
The secondary CVS safety outcome measures Biochemical markers for myocardial necrosis high sensitive troponin I - hsTnI creatine kinase MB fraction - CK-MB will be evaluated on blood samples taken before and 12 hours after cardioversion ST-segment changes will be measured in lead II baseline and 10 s post-shock and 12-lead ECG Complications after cardioversion will be measured during 2 hours follow-up period in the ICCU
Detailed Description:
Background
External defibrillators are routinely used for treatment of lethal ventricular arrhythmias defibrillation as well as atrial and non-lethal ventricular arrhythmias synchronized CVS Commercially available defibrillators generate direct current DC shock with various waveforms using distinct technologies These waveforms are suggested to have different efficacy and safety aiming at a positive effect with lower cumulative energy smaller number of shocks and less post-shock complications and myocardial injury Therefore the efficacy and safety of different waveforms has been an object of continuous interest and clinical investigations over the last years Although the superiority of biphasic over monophasic waveforms is well established the relative efficacy and safety of the available biphasic waveforms is not clear
Most defibrillator manufacturers use the biphasic truncated exponential BTE waveform Almost all BTE defibrillators are embedding the impedance compensation technology which adapts the pulse duration for proper delivery of the selected energy However various pulse commutation concepts produce differently shaped waveforms
rectilinear impedance compensation with constant pulse duration
standard truncated exponential impedance compensation with constant tilt
pulsed impedance compensation with constant duty cycle and constant tilt Clinical studies with patients presenting with shockable life-threatening arrhythmias are difficult to perform for ethical and practical reasons Several studies have therefore included patients requiring elective CVS for atrial arrhythmias who are able to give consent and also present a more controlled population Elective CVS is a standard treatment for patients with atrial arrhythmias and is performed as a day case procedure under general anesthesia The investigators bibliographic research found 6 studies from which the dose-response curves of 4 rectilinear 7 standard truncated exponential and 3 pulsed waveforms have been drawn Although the major disparities between the studies success accounted at different delays after CVS rhythm inhomogeneity different population sizes different selected energy levels etc the dose-response curves concentrate within 85-95 success rate and 300-500 joules J cumulative energy More data on the efficacy of the pulsed waveform during CVS are needed
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 quantification of shock-induced myocardial injuries is based on measurements of the hsTnI biomarker after CVS The safety of shocks contemplates any other complications after CVS such as apnea arrhythmias etc The variety of safety outcomes for different BTE waveforms is not clear
Considering that little published data are available on pulsed waveforms this study aims to compare the pulsed biphasic waveform to a standard truncated exponential waveform in respect of efficacy and safety in elective CVS of atrial fibrillation
Methods
Study population All patients admitted for elective CVS of atrial fibrillation AFIB in ICCU- National Heart Hospital NHH will be potentially eligible for the study Informed consent will be obtained from all eligible patients prior to CVS Patients declining to participate in the study will receive treatment according to the hospital protocol
Cardiologists in ICCU-NHH will check the eligibility of each patient following the detailed list of inclusion and exclusion criteria in section Eligibility Criteria based on the documented pre-treatment data duration of AFIB concomitant diseases thyroid dysfunction transesophageal echocardiographic TEE measurements
Additionally eligibility will be verified through pre-CVS medical exams and routine blood test within 24 hours before CVS including hsTnI measurements on the day of CVS
Study design 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-NHH 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-NHH 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 CVS 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 CVS 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 hospital file ID age gender weight height body mass index body surface area will be taken
Pre-treatment data will be read from the patient dossier
All concomitant diseases
All medications during the previous 7 days before CVS
Left atrium dimensions left ventricle dimensions and volumes ejection fraction EF by transthoracic echocardiography during the last month
TEE will be performed for all patients within 1 to 5 days before CVS except if contraindications of TEE exist presence of cardiac thrombus and spontaneous echo contrast will be checked
Duration of index AFIB in days
European Heart Rhythm Association EHRA class score of symptoms from index AFIB
American Society of Anaesthesiologists Score ASA
Signs of heart failure before CVS and on the day before CVS Standard blood test taken 24h before CVS will be documented Appropriate standard anticoagulation with unfractionated heparin UFH or acenocoumarol or direct oral anticoagulants DOAC is to be applied before and after CVS
The patient will be in fasting condition before CVS If needed the chest will be shaved before CVS so that the self-adhesive defibrillation pads can be stick intact to the skin
The anesthesia will be conducted by an anesthesiologist with slow intravenous injection of Propofol adjusted individually to reach deep sedation The individual Propofol dose mg per kg bodyweight will be documented
CVS protocol
The CVS procedure is performed in ICCU by a cardiologist and anesthesiologist Defibrillator pads are placed according to the manufacturer user guides Standard self-adhesive defibrillation pads recommended by specific defibrillators manufacturer will be used
Defibrillator use The time-interval interval between consecutive shocks is 1 minute The energy of consecutive shocks follows pre-defined protocol The protocol stops at successful CVS sinus rhythm at 1 minute 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 recorder Defimpulse 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 needed during the CVS intervention The use of the Defimpulse has been approved by the NHH Ethical Committee
Blood samples standard 12-lead ECG blood pressure and heart rate is obtained at baseline
Continuous ECG in 3 peripheral leads I II III is recorded during the CVS procedure ST-segment deviation is measured on the first cardiac complex after 10 s post-shock 80 ms after J point in lead II
Standard 12-lead ECG is recorded 5 minutes after CVS 24 h after CVS at discharge if the discharge day is different from 24 h after CVS
Heart rate and blood pressure are measured 3 times after CVS immediately 1 hour and 2 hours after the last shock
Follow-up period in ICCU 2 hours of duration Potential complications after CVS are recorded
1 Presence of apnea
2 Presence of arrhythmias
3 Record of any other medication at CVS and during the follow-up period
Follow-up period in the Cardiology Clinic 24 hours of duration
1 blood samples to analyze CK-MB and hsTnI 12 hours - 4 hours after CVS
2 Clinical exam with heart rate and blood pressure 2 times on the day of CVS
3 ECG and blood pressure on the next day after CVS
4 Any complications before discharge
Statistics
Primary endpoint The statistical analysis is designed for a non-inferiority comparison between the two defibrillators in respect of their cumulative energies actually delivered A non-inferiority margin of 50J is chosen as the absolute difference in cumulative delivered energy at the end of the CVS study It is estimated that a total of 62 patients 31 per group allows a study power to show non-inferiority of 80 with a one-sided type I error rate of 005
Continuous variables cumulative energy number of shocks cardiac troponin levels etc 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 eg cumulative success rate are expressed as percentages and compared using the Chi-square or Fishers exact test where appropriate P 005 is considered statistically significant for all comparisons
Ethics All patients are signed a written informed consent prior to the CVS and receive the standard hospital procedures during CVS accepted in the NHH and approved by the NHH Ethical Committee Both defibrillators included in this study are approved for clinical use and both are used on a daily basis
Data anonymization policy is respected In order to ensure the medical confidentiality no information about the patient intervention place and date age gender name diagnosis etc is entered in the defibrillators An identification number are given to each patient by the dedicated measurement recorder Defimpulse This number and the recording data are properties of the principal investigator Approval from the NHH Ethical Committee concerning the use of the Defimpulse during the CVS intervention has been obtained
External defibrillators are routinely used for treatment of lethal ventricular arrhythmias defibrillation as well as atrial and non-lethal ventricular arrhythmias synchronized CVS Commercially available defibrillators generate direct current DC shock with various waveforms using distinct technologies These waveforms are suggested to have different efficacy and safety aiming at a positive effect with lower cumulative energy smaller number of shocks and less post-shock complications and myocardial injury Therefore the efficacy and safety of different waveforms has been an object of continuous interest and clinical investigations over the last years Although the superiority of biphasic over monophasic waveforms is well established the relative efficacy and safety of the available biphasic waveforms is not clear
Most defibrillator manufacturers use the biphasic truncated exponential BTE waveform Almost all BTE defibrillators are embedding the impedance compensation technology which adapts the pulse duration for proper delivery of the selected energy However various pulse commutation concepts produce differently shaped waveforms
rectilinear impedance compensation with constant pulse duration
standard truncated exponential impedance compensation with constant tilt
pulsed impedance compensation with constant duty cycle and constant tilt Clinical studies with patients presenting with shockable life-threatening arrhythmias are difficult to perform for ethical and practical reasons Several studies have therefore included patients requiring elective CVS for atrial arrhythmias who are able to give consent and also present a more controlled population Elective CVS is a standard treatment for patients with atrial arrhythmias and is performed as a day case procedure under general anesthesia The investigators bibliographic research found 6 studies from which the dose-response curves of 4 rectilinear 7 standard truncated exponential and 3 pulsed waveforms have been drawn Although the major disparities between the studies success accounted at different delays after CVS rhythm inhomogeneity different population sizes different selected energy levels etc the dose-response curves concentrate within 85-95 success rate and 300-500 joules J cumulative energy More data on the efficacy of the pulsed waveform during CVS are needed
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 quantification of shock-induced myocardial injuries is based on measurements of the hsTnI biomarker after CVS The safety of shocks contemplates any other complications after CVS such as apnea arrhythmias etc The variety of safety outcomes for different BTE waveforms is not clear
Considering that little published data are available on pulsed waveforms this study aims to compare the pulsed biphasic waveform to a standard truncated exponential waveform in respect of efficacy and safety in elective CVS of atrial fibrillation
Methods
Study population All patients admitted for elective CVS of atrial fibrillation AFIB in ICCU- National Heart Hospital NHH will be potentially eligible for the study Informed consent will be obtained from all eligible patients prior to CVS Patients declining to participate in the study will receive treatment according to the hospital protocol
Cardiologists in ICCU-NHH will check the eligibility of each patient following the detailed list of inclusion and exclusion criteria in section Eligibility Criteria based on the documented pre-treatment data duration of AFIB concomitant diseases thyroid dysfunction transesophageal echocardiographic TEE measurements
Additionally eligibility will be verified through pre-CVS medical exams and routine blood test within 24 hours before CVS including hsTnI measurements on the day of CVS
Study design 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-NHH 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-NHH 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 CVS 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 CVS 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 hospital file ID age gender weight height body mass index body surface area will be taken
Pre-treatment data will be read from the patient dossier
All concomitant diseases
All medications during the previous 7 days before CVS
Left atrium dimensions left ventricle dimensions and volumes ejection fraction EF by transthoracic echocardiography during the last month
TEE will be performed for all patients within 1 to 5 days before CVS except if contraindications of TEE exist presence of cardiac thrombus and spontaneous echo contrast will be checked
Duration of index AFIB in days
European Heart Rhythm Association EHRA class score of symptoms from index AFIB
American Society of Anaesthesiologists Score ASA
Signs of heart failure before CVS and on the day before CVS Standard blood test taken 24h before CVS will be documented Appropriate standard anticoagulation with unfractionated heparin UFH or acenocoumarol or direct oral anticoagulants DOAC is to be applied before and after CVS
The patient will be in fasting condition before CVS If needed the chest will be shaved before CVS so that the self-adhesive defibrillation pads can be stick intact to the skin
The anesthesia will be conducted by an anesthesiologist with slow intravenous injection of Propofol adjusted individually to reach deep sedation The individual Propofol dose mg per kg bodyweight will be documented
CVS protocol
The CVS procedure is performed in ICCU by a cardiologist and anesthesiologist Defibrillator pads are placed according to the manufacturer user guides Standard self-adhesive defibrillation pads recommended by specific defibrillators manufacturer will be used
Defibrillator use The time-interval interval between consecutive shocks is 1 minute The energy of consecutive shocks follows pre-defined protocol The protocol stops at successful CVS sinus rhythm at 1 minute 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 recorder Defimpulse 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 needed during the CVS intervention The use of the Defimpulse has been approved by the NHH Ethical Committee
Blood samples standard 12-lead ECG blood pressure and heart rate is obtained at baseline
Continuous ECG in 3 peripheral leads I II III is recorded during the CVS procedure ST-segment deviation is measured on the first cardiac complex after 10 s post-shock 80 ms after J point in lead II
Standard 12-lead ECG is recorded 5 minutes after CVS 24 h after CVS at discharge if the discharge day is different from 24 h after CVS
Heart rate and blood pressure are measured 3 times after CVS immediately 1 hour and 2 hours after the last shock
Follow-up period in ICCU 2 hours of duration Potential complications after CVS are recorded
1 Presence of apnea
2 Presence of arrhythmias
3 Record of any other medication at CVS and during the follow-up period
Follow-up period in the Cardiology Clinic 24 hours of duration
1 blood samples to analyze CK-MB and hsTnI 12 hours - 4 hours after CVS
2 Clinical exam with heart rate and blood pressure 2 times on the day of CVS
3 ECG and blood pressure on the next day after CVS
4 Any complications before discharge
Statistics
Primary endpoint The statistical analysis is designed for a non-inferiority comparison between the two defibrillators in respect of their cumulative energies actually delivered A non-inferiority margin of 50J is chosen as the absolute difference in cumulative delivered energy at the end of the CVS study It is estimated that a total of 62 patients 31 per group allows a study power to show non-inferiority of 80 with a one-sided type I error rate of 005
Continuous variables cumulative energy number of shocks cardiac troponin levels etc 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 eg cumulative success rate are expressed as percentages and compared using the Chi-square or Fishers exact test where appropriate P 005 is considered statistically significant for all comparisons
Ethics All patients are signed a written informed consent prior to the CVS and receive the standard hospital procedures during CVS accepted in the NHH and approved by the NHH Ethical Committee Both defibrillators included in this study are approved for clinical use and both are used on a daily basis
Data anonymization policy is respected In order to ensure the medical confidentiality no information about the patient intervention place and date age gender name diagnosis etc is entered in the defibrillators An identification number are given to each patient by the dedicated measurement recorder Defimpulse This number and the recording data are properties of the principal investigator Approval from the NHH Ethical Committee concerning the use of the Defimpulse during the CVS 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?:
None
Is an FDA AA801 Violation?:
None