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Comparison of Oxygen Interventions and Defibrillator Efficiency (CODE)

Primary Purpose

Atrial Fibrillation, Atrial Flutter

Status
Terminated
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Cardioversion with a pulsed biphasic waveform
Normoxia during cardioversion
Cardioversion with a biphasic truncated exponential waveform
Hyperoxia during cardioversion
Sponsored by
Randers Regional Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring Cardioversion, Cardiac Arrythmias, Myocardial Injury, Defibrillators, Biomarkers

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Atrial fibrillation or -flutter

Exclusion Criteria:

  • Patients <18 years of age
  • Pregnancy
  • Haemodynamically unstable patients
  • Other arrhythmias
  • Untreated hyperthyroidism

Sites / Locations

  • Randers Regional Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Active Comparator

Active Comparator

Arm Label

1 ("Standard": Oxygen / LIFEPAK 20)

2 (room air / LIFEPAK 20)

3 (Oxygen / Schiller Defigard 5000)

4 (Room air / Schiller Defigard 5000)

Arm Description

Intervention: Cardioversion with a biphasic truncated exponential waveform Intervention: Hyperoxia during cardioversion

Intervention: Cardioversion with a biphasic truncated exponential waveform Intervention: Normoxia during cardioversion

Intervention: Cardioversion with a pulsed biphasic waveform Intervention: Hyperoxia during cardioversion

Intervention: Cardioversion with a pulsed biphasic waveform Intervention: Normoxia during cardioversion

Outcomes

Primary Outcome Measures

Change in Hs-cTnI and Hs-cTnT for room air versus hyperoxia
High sensitive cardiac Troponin I (Hs-cTnI) and -T (Hs-cTnT) are biomarkers for myocardial injury. Cardiac troponins are measured in plasma as ng/L. Change in cardiac troponins (4 hours after cardioversion - pre-cardioversion) will be compared between room air and hyperoxia.
Defibrillator Efficiency: Proportion of patients in sinus rhythm four hours post cardioversion
Proportion of patients in sinus rhythm four hours post cardioversion

Secondary Outcome Measures

Cardiac rhythm and change in biomarkers
Biomarkers will be measured by NT-pro-BNP (ng/L) and Copeptin (pmol/L) at baseline, discharge and at a 3 months follow up visit in the outpatient Clinic. Change in biomarker levels will be compared for patients treated with hyperoxia and room air.
Echocardiography
Cardiac function will be evaluated.

Full Information

First Posted
March 18, 2014
Last Updated
May 22, 2018
Sponsor
Randers Regional Hospital
Collaborators
Aarhus University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02317029
Brief Title
Comparison of Oxygen Interventions and Defibrillator Efficiency
Acronym
CODE
Official Title
A Comparison of Two Biphasic Waveforms and Impact of Oxygen on Myocardial Injury Following Cardioversion
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Terminated
Why Stopped
A major adverse event occured (pulsed biphasic waveform arm).
Study Start Date
September 2013 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Randers Regional Hospital
Collaborators
Aarhus University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Background: Cardiac arrhythmias can be terminated by electrical current applied by an external defibrillator. This treatment, named cardioversion, has been used for decades in the treatment of atrial fibrillation. Several kinds of defibrillators exist, though the relative efficacy and safety of these defibrillators is not clear. During cardioversion, oxygen is being administered, and it has been a long-held belief that oxygen is always beneficial for the patient. This is now being challenged by recent studies suggesting excessive oxygenation to be potentially dangerous for the patients. Objective: To compare the efficiency and safety of two different defibrillators To investigate the effects of excessive oxygen on injury of the heart following cardioversion. Experimental design: Patients will be recruited at the outpatient clinic at the Department of Cardiology, Regional Hospital of Randers, Denmark as a part of the pre-cardioversion check. Patients will be randomized to cardioversion using one of two defibrillators and randomized to treatment with room air or 100% oxygen. The cardiac condition will be measured by blood samples before cardioversion, 4 hours after cardioversion and 3 months after cardioversion. Heart rhythm will be measured by ECG before cardioversion, 1 minute-, 30 minutes- and 4 hours after cardioversion.
Detailed Description
Background: Treatment of cardiac arrest includes effective chest compressions, ventilation using high flow oxygen and the delivery of electric shocks (cardioversion). Prompt termination of cardiac arrhythmias and sufficient airway handling including oxygenation are crucial factors for patient outcome. Studies suggest that cardioversion itself may induce myocardial injury; however it is currently unknown whether hyperoxia exacerbate this injury. Currently, several different biphasic waveforms are in use for cardioversion.The comparative efficacy and safety of these waveforms has not been compared in clinical studies. Commercially available defibrillators use different electrical waveforms that may affect the efficacy of external defibrillation. Although the superiority of biphasic over monophasic waveforms is well established, the relative efficacy and safety of the available biphasic waveforms is not clear. The long held belief that oxygen (O2) is always beneficial for ill and injured patients is being challenged by recent studies suggesting that excessive oxygenation may result in free-radical mediated tissue damage, resulting in increased morbidity and mortality. Recent guidelines suggest that O2 should be 'titrated' to achieve an appropriate target saturation of 94-98% rather than being administered in an all-or-nothing fashion, particularly in patients with myocardial ischemia or those following resuscitation from cardiac arrest. The Scottish Intercollegiate Guidelines Network (SIGN), British Thoracic Society, National Institute of Health Care Excellence (NICE), European Resuscitation Council and other respected bodies all restrict O2 use to those with hypoxemia, pulmonary oedema or continuing myocardial ischemia, based on expert opinion and pathophysiological reasoning rather than hard evidence. Studies using patients presenting with shockable life-threatening arrhythmias (e.g. ventricular fibrillation) are difficult to perform for ethical and practical reasons. This study will therefore use patients requiring elective cardioversion for atrial arrhythmias, who are able to give consent and also present a more controlled population. Elective cardioversion is a standard treatment for patients with atrial arrhythmias and is performed as a day case procedure under general anaesthesia. This study has the following aims: To compare a standard biphasic waveform with a newer pulsed biphasic waveform on which there is little published data To compare the effect of hyperoxia and room air on myocardial injury following cardioversion on which there is no published data. Methods: All patients admitted for cardioversion for atrial fibrillation and flutter will be potentially eligible for the study. Patients will be recruited at the Regional Hospital of Randers as a part of the pre-cardioversion check. This is the first contact to patients, and they will receive oral and written information. The oral and written information will be given by a doctor and/or the primary investigator. The information will be given in a quiet setting, and the patients may ask questions about the study. It will be possible for the patient to have a companion present. Informed consent will be obtained from all participants during the pre-cardioversion check or alternatively prior to cardioversion allowing the patient to have a companion present before consent is given. Patients declining to participate in the study will receive treatment according to the standard protocol. Patients with atrial fibrillation or flutter for ≤48 hours may be cardioverted immediately. Patients with atrial fibrillation or flutter for >48 hours will be required to have a documented weekly international normalized ratio (INR) ≥2.0 (including within 48 hours of cardioversion) or treatment with dabigatranetexilat for three weeks or longer. Alternatively, a transoesophageal echocardiogram documenting absence of intracardiac thrombi is accepted and cardioversion can be performed on treatment with low molecular weight heparin. All patients will be discharged with a recommendation for therapeutic anticoagulation according to current guidelines. Patient preparation Patients will be consulted prior to cardioversion; standard blood test will be taken, blood pressure, height and weight will be measured. Information from patient chart (age, gender, morbidity, co-morbidity and medication) will be used to define baseline values. In addition New York Heart Association Functional Classification (NYHA), European Heart Rhythm Association AF-related symptoms (EHRA), American Society of Anaesthesiologists Score (ASA) and Canadian Cardiovascular Society Grading System (CCS) will be recorded during history taking. In addition, information from the patient chart regarding comorbidities, medication etc. will be obtained. Cardioversion protocol Blood samples, ECG, blood pressure, oxygen saturation and heart rate will be obtained at baseline and all patients will receive 0.5 mg Rapifen i.v. All patients will be treated with 100 % oxygen or room air, 10-15 L/ minute for 3 minutes before administration of Propofol. All patients will be treated with Propofol 1 mg i.v./kg bodyweight with subsequent 20 mg boluses as needed. Before cardioversion PaO2 will be measured by arterial blood gas (1 mL). Follow up All patients will be seen at the outpatient clinic after 3 months. Echocardiography will be performed and biomarkers will be measured. Patients will be classified after NYHA, EHRA, ASA and CCS. Statistics Regarding waveforms: Assuming the cumulative efficacy, defined as success rate after all delivered shocks, for one of the waveforms is 95%, and for the other waveform ≥80%, a sample size of 75 patients in each group is needed to achieve a power of 80% in rejecting the null hypothesis (that the difference in cumulative efficacy is ≥15%). Continuous variables (number of shocks, delivered energy etc.) are expressed as mean ± SD or median values and compared with Students t-test or equivalent non-parametric test. Categorical variables (e.g. successful cardioversion) are expressed as percentages and compared using the Chi-square or Fisher's exact test (where appropriate). P ≤ 0.05 is considered statistically significant for all comparisons. Regarding oxygen treatment: It is estimated that 150 patients will be sufficient for the study. After treatment of 60 patients, an interim futility test will be performed. Biomarker data will be analyzed using parametric and non-parametric tests as appropriate. P ≤ 0.05 is considered statistically significant. Ethics Approval from The Danish Research Ethics Committee and Danish Data Protection Agency has been obtained. The project will be performed in accordance with the Danish Health Act.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Atrial Flutter
Keywords
Cardioversion, Cardiac Arrythmias, Myocardial Injury, Defibrillators, Biomarkers

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
134 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1 ("Standard": Oxygen / LIFEPAK 20)
Arm Type
Experimental
Arm Description
Intervention: Cardioversion with a biphasic truncated exponential waveform Intervention: Hyperoxia during cardioversion
Arm Title
2 (room air / LIFEPAK 20)
Arm Type
Active Comparator
Arm Description
Intervention: Cardioversion with a biphasic truncated exponential waveform Intervention: Normoxia during cardioversion
Arm Title
3 (Oxygen / Schiller Defigard 5000)
Arm Type
Active Comparator
Arm Description
Intervention: Cardioversion with a pulsed biphasic waveform Intervention: Hyperoxia during cardioversion
Arm Title
4 (Room air / Schiller Defigard 5000)
Arm Type
Active Comparator
Arm Description
Intervention: Cardioversion with a pulsed biphasic waveform Intervention: Normoxia during cardioversion
Intervention Type
Device
Intervention Name(s)
Cardioversion with a pulsed biphasic waveform
Other Intervention Name(s)
Schiller Defigard 5000 (SCHILLER AG, Baar, Switzerland)
Intervention Description
Cardioversion will be performed by a pulsed biphasic (Multipulse Biowave®) waveform (Schiller Defigard 5000) with an energy setting of 90J, 120J, 150J, 200J. Primary endpoint: The proportion of patients in sinus rhythm four hours post cardioversion.
Intervention Type
Procedure
Intervention Name(s)
Normoxia during cardioversion
Other Intervention Name(s)
room air during cardioversion
Intervention Description
Patients will be treated with room air with a flow of 10-15 L/minute for 3 minutes prior to cardioversion and nasal room air with a flow of 3 L/minute for 30 minutes following cardioversion
Intervention Type
Device
Intervention Name(s)
Cardioversion with a biphasic truncated exponential waveform
Other Intervention Name(s)
LIFEPAK 20, Physio Control Inc., Redmond, WA, USA
Intervention Description
Cardioversion will be performed by a biphasic truncated exponential waveform (LIFEPAK 20), with a energy setting of 100J, 150J, 200J, 250J. Primary endpoint: The proportion of patients in sinus rhythm four hours post cardioversion.
Intervention Type
Procedure
Intervention Name(s)
Hyperoxia during cardioversion
Other Intervention Name(s)
100% oxygen during cardioversion
Intervention Description
Patients will be treated with 100% oxygen with a flow of 10-15 L/minute for 3 minutes prior to cardioversion and nasal 100% oxygen with a flow of 3 L/minute for 30 minutes following cardioversion
Primary Outcome Measure Information:
Title
Change in Hs-cTnI and Hs-cTnT for room air versus hyperoxia
Description
High sensitive cardiac Troponin I (Hs-cTnI) and -T (Hs-cTnT) are biomarkers for myocardial injury. Cardiac troponins are measured in plasma as ng/L. Change in cardiac troponins (4 hours after cardioversion - pre-cardioversion) will be compared between room air and hyperoxia.
Time Frame
Change measured from 2 hours before and 4 hours after cardioversion
Title
Defibrillator Efficiency: Proportion of patients in sinus rhythm four hours post cardioversion
Description
Proportion of patients in sinus rhythm four hours post cardioversion
Time Frame
Heart rhythm measured four hours after cardioversion
Secondary Outcome Measure Information:
Title
Cardiac rhythm and change in biomarkers
Description
Biomarkers will be measured by NT-pro-BNP (ng/L) and Copeptin (pmol/L) at baseline, discharge and at a 3 months follow up visit in the outpatient Clinic. Change in biomarker levels will be compared for patients treated with hyperoxia and room air.
Time Frame
Biomarkers will be measured within 2 hours before, 4 hours after and 3 months after cardioversion. ECG will be recorded after 1 minute, 30 minutes and four hours after cardioversion.
Title
Echocardiography
Description
Cardiac function will be evaluated.
Time Frame
Performed at baseline, 2-4 hours after and 3 months following cardioversion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Atrial fibrillation or -flutter Exclusion Criteria: Patients <18 years of age Pregnancy Haemodynamically unstable patients Other arrhythmias Untreated hyperthyroidism
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bo Løfgren, MD, PhD
Organizational Affiliation
Randers Regional Hospital
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Kasper G. Lauridsen, MB
Organizational Affiliation
Randers Regional Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anders S. Schmidt, MB
Organizational Affiliation
Randers Regional Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Randers Regional Hospital
City
Randers
State/Province
Midtjylland
ZIP/Postal Code
8970
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
29421020
Citation
Lauridsen KG, Schmidt AS, Adelborg K, Bach L, Hornung N, Jepsen SM, Deakin CD, Rickers H, Lofgren B. Effects of hyperoxia on myocardial injury following cardioversion-A randomized clinical trial. Am Heart J. 2018 Feb;196:97-104. doi: 10.1016/j.ahj.2017.10.006. Epub 2017 Oct 14.
Results Reference
derived
PubMed Identifier
28275066
Citation
Schmidt AS, Lauridsen KG, Adelborg K, Torp P, Bach LF, Jepsen SM, Hornung N, Deakin CD, Rickers H, Lofgren B. Cardioversion Efficacy Using Pulsed Biphasic or Biphasic Truncated Exponential Waveforms: A Randomized Clinical Trial. J Am Heart Assoc. 2017 Mar 8;6(3):e004853. doi: 10.1161/JAHA.116.004853.
Results Reference
derived

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Comparison of Oxygen Interventions and Defibrillator Efficiency

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