AMSA and Amiodarone Study in Cardiac Arrest

Out-Of-Hospital Cardiac Arrest Clinical Trial

— MOSAIC  

Official title:

aMsa and amiOdarone Study in cArdiaC Arrest

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04997980
• Other study ID #: IRCCSPSM 1
• Status: Completed
• Start date: January 1, 2015
• Est. completion date: December 31, 2023

Study information

• Verified date: March 2024
• Source: IRCCS Policlinico S. Matteo
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Investigators' aim is to assess whether the administration of amiodarone during resuscitation could cause a reduction of the values of the amplitude spectral area (AMSA).

Amiodarone is recommended for the treatment of cardiac arrest due to ventricular tachycardia/ventricular fibrillation (VT/VF) ( with a low level of recommendation cause of conflicting results. AMSA is a parameter expressing the amplitude of VF and it has been shown to predict defibrillation success and the return of spontaneous circulation (ROSC). No data are available so far about the impact of amiodarone administration on AMSA values.

Description:

The primary study endpoint of the present study is to determine whether patients who received amiodarone during advanced resuscitation had lower values of AMSA as compared to those who did not receive amiodarone.

Secondary endpoints

The secondary endpoints of this study are:

1. To assess, after correction for confounders, the rate of successful defibrillation, the rate of ROSC and the rate of short-term survival (survived event or survival to hospital discharge according to the available data) both in the amiodarone and non-amiodarone group.

2. To assess the role of AMSA for shock success and ROSC prediction in amiodarone group and in non-amiodarone group.

Type of study. This is a multicentre study based on a retrospective analysis of prospectically collected data.

Study population All the out-of-hospital cardiac arrests (OHCA) which occurred from January 1st, 2015 to December 31st, 2020 will be considered for the present study. In the analysis the investigators will include only those patients who received at least one shock for ventricular fibrillation during advanced resuscitation regardless whether or not the presenting rhythm was shockable or non-shockable.

The study cohort will involve cases retrieved from the Lombardia CARe registry (Lombardia Cardiac Arrest Registry NCT03197142), from the registry of Oslo and Vestfold

Data Collection Data from different databases will be integrated and combined in a single ad hoc database for statistical analysis.

For every shock, both pre-shock carbon dioxide at the end ot the tidal volume (ETCO2) and pre-shock AMSA will be calculated. The median ETCO2 value in the minute before the shock (METCO2) will be computed automatically either from a capnogram, when available, applying the algorithm described by Aramendi et al, or from the defibrillator with a ETCO2 monitoring feature. AMSA will be computed using a 2-second-pre-shock ECG interval, free of chest compression artifacts, leaving a 1-second guard before the shock. The electrocardiogram (ECG) will be bandpass filtered (0.5-30Hz) and the fast Fourier transform computed to obtain AMSA in the 2-48 Hz bandwidth.

For each patient all the pre-hospital variables will be included according to the 2014 Utstein recommendations and the number of shocks will be computed. The mean value of both ETCO2 and of AMSA will be calculated.

Statistical analysis Categorical variables will be compared with the Chi-square test and presented as number and percentage. Continuous variables will be compared with the t-test and presented as mean ± standard deviation, or compared with the Mann-Whitney test and presented as median and interquartile range (IQR) according to normal distribution tested with the D'Agostino-Pearson test. A multivariable regression model will be fitted both for shock success and for ROSC (including all non-correlated potential predictors) and to test the effect of amiodarone on AMSA values after correction for confounders.

The values of AMSA in the amiodarone and in the non-amiodarone group will then be compared in two groups of shocks randomly matched and identified via propensity score matching, so that they are homogeneous for time to shock, pre-shock ETCO2, outcome of defibrillation and the age of the patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 629
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 100 Years

Eligibility

Inclusion Criteria:

clinical:

• patients with out-of-hospital cardiac arrest

• shockable presenting rhythm

• resuscitation attempted

• advanced resuscitation attempted

technical: - VF cardiac arrest (and not VT)

Exclusion Criteria:

clinical:

• non-shockable presenting rhythm

• resuscitation not attempted

technical:

• AMSA not evaluable

Related Conditions & MeSH terms

• Heart Arrest
• Out-of-Hospital Cardiac Arrest

Intervention

Drug:
• Amiodarone Injection

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Norway	Oslo University Hospital	Oslo
Norway	Vestfold Hospital trust	Tønsberg
Spain	BioRes Research Group	Bilbao

Sponsors (4)

Lead Sponsor	Collaborator
IRCCS Policlinico S. Matteo	Oslo University Hospital, The Hospital of Vestfold, University of the Basque Country (UPV/EHU)

Countries where clinical trial is conducted

Italy,  Norway,  Spain, 

References & Publications (28)

Aiello S, Perez M, Cogan C, Baetiong A, Miller SA, Radhakrishnan J, Kaufman CL, Gazmuri RJ. Real-Time Ventricular Fibrillation Amplitude-Spectral Area Analysis to Guide Timing of Shock Delivery Improves Defibrillation Efficacy During Cardiopulmonary Resuscitation in Swine. J Am Heart Assoc. 2017 Nov 4;6(11):e006749. doi: 10.1161/JAHA.117.006749. — View Citation

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Frigerio L, Baldi E, Aramendi E, Chicote B, Irusta U, Contri E, Palo A, Compagnoni S, Fracchia R, Iotti G, Oltrona Visconti L, Savastano S; Lombardia CARe Researchers. End-tidal carbon dioxide (ETCO2) and ventricular fibrillation amplitude spectral area (AMSA) for shock outcome prediction in out-of-hospital cardiac arrest. Are they two sides of the same coin? Resuscitation. 2021 Mar;160:142-149. doi: 10.1016/j.resuscitation.2020.10.032. Epub 2020 Nov 10. — View Citation

Hohnloser SH, Dorian P, Roberts R, Gent M, Israel CW, Fain E, Champagne J, Connolly SJ. Effect of amiodarone and sotalol on ventricular defibrillation threshold: the optimal pharmacological therapy in cardioverter defibrillator patients (OPTIC) trial. Circulation. 2006 Jul 11;114(2):104-9. doi: 10.1161/CIRCULATIONAHA.106.618421. Epub 2006 Jul 3. — View Citation

Hulleman M, Salcido DD, Menegazzi JJ, Souverein PC, Tan HL, Blom MT, Koster RW. Predictive value of amplitude spectrum area of ventricular fibrillation waveform in patients with acute or previous myocardial infarction in out-of-hospital cardiac arrest. Resuscitation. 2017 Nov;120:125-131. doi: 10.1016/j.resuscitation.2017.08.219. Epub 2017 Aug 24. — View Citation

Hulleman M, Salcido DD, Menegazzi JJ, Souverein PC, Tan HL, Blom MT, Koster RW. Ventricular fibrillation waveform characteristics in out-of-hospital cardiac arrest and cardiovascular medication use. Resuscitation. 2020 Jun;151:173-180. doi: 10.1016/j.resuscitation.2020.02.027. Epub 2020 Mar 10. — View Citation

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Kudenchuk PJ, Cobb LA, Copass MK, Cummins RO, Doherty AM, Fahrenbruch CE, Hallstrom AP, Murray WA, Olsufka M, Walsh T. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med. 1999 Sep 16;341(12):871-8. doi: 10.1056/NEJM199909163411203. — View Citation

Kudenchuk PJ, Leroux BG, Daya M, Rea T, Vaillancourt C, Morrison LJ, Callaway CW, Christenson J, Ornato JP, Dunford JV, Wittwer L, Weisfeldt ML, Aufderheide TP, Vilke GM, Idris AH, Stiell IG, Colella MR, Kayea T, Egan D, Desvigne-Nickens P, Gray P, Gray R, Straight R, Dorian P; Resuscitation Outcomes Consortium Investigators. Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo). Circulation. 2017 Nov 28;136(22):2119-2131. doi: 10.1161/CIRCULATIONAHA.117.028624. Epub 2017 Sep 13. — View Citation

Marinchak RA, Friehling TD, Kline RA, Stohler J, Kowey PR. Effect of antiarrhythmic drugs on defibrillation threshold: case report of an adverse effect of mexiletine and review of the literature. Pacing Clin Electrophysiol. 1988 Jan;11(1):7-12. doi: 10.1111/j.1540-8159.1988.tb03925.x. — View Citation

Ong ME, Pellis T, Link MS. The use of antiarrhythmic drugs for adult cardiac arrest: a systematic review. Resuscitation. 2011 Jun;82(6):665-70. doi: 10.1016/j.resuscitation.2011.02.033. Epub 2011 Mar 27. — View Citation

Ristagno G, Gullo A, Berlot G, Lucangelo U, Geheb E, Bisera J. Prediction of successful defibrillation in human victims of out-of-hospital cardiac arrest: a retrospective electrocardiographic analysis. Anaesth Intensive Care. 2008 Jan;36(1):46-50. doi: 10.1177/0310057X0803600108. — View Citation

Ristagno G, Li Y, Fumagalli F, Finzi A, Quan W. Amplitude spectrum area to guide resuscitation-a retrospective analysis during out-of-hospital cardiopulmonary resuscitation in 609 patients with ventricular fibrillation cardiac arrest. Resuscitation. 2013 Dec;84(12):1697-703. doi: 10.1016/j.resuscitation.2013.08.017. Epub 2013 Sep 1. — View Citation

Ristagno G, Mauri T, Cesana G, Li Y, Finzi A, Fumagalli F, Rossi G, Grieco N, Migliori M, Andreassi A, Latini R, Fornari C, Pesenti A; Azienda Regionale Emergenza Urgenza Research Group. Amplitude spectrum area to guide defibrillation: a validation on 1617 patients with ventricular fibrillation. Circulation. 2015 Feb 3;131(5):478-87. doi: 10.1161/CIRCULATIONAHA.114.010989. Epub 2014 Dec 2. Erratum In: Circulation. 2015 May 19;131(20):e502. — View Citation

Ruggeri L, Semeraro F, Ristagno G. Amplitude spectrum area: The "clairvoyance" during resuscitation in the era of predictive medicine. Resuscitation. 2017 Nov;120:A5-A6. doi: 10.1016/j.resuscitation.2017.09.011. Epub 2017 Sep 18. No abstract available. — View Citation

Salcido DD, Schmicker RH, Kime N, Buick JE, Cheskes S, Grunau B, Zellner S, Zive D, Aufderheide TP, Koller AC, Herren H, Nuttall J, Sundermann ML, Menegazzi JJ; Resuscitation Outcomes Consortium Investigators. Effects of intra-resuscitation antiarrhythmic administration on rearrest occurrence and intra-resuscitation ECG characteristics in the ROC ALPS trial. Resuscitation. 2018 Aug;129:6-12. doi: 10.1016/j.resuscitation.2018.05.028. Epub 2018 May 24. — View Citation

Sanfilippo F, Corredor C, Santonocito C, Panarello G, Arcadipane A, Ristagno G, Pellis T. Amiodarone or lidocaine for cardiac arrest: A systematic review and meta-analysis. Resuscitation. 2016 Oct;107:31-7. doi: 10.1016/j.resuscitation.2016.07.235. Epub 2016 Aug 3. — View Citation

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Soar J, Berg KM, Andersen LW, Bottiger BW, Cacciola S, Callaway CW, Couper K, Cronberg T, D'Arrigo S, Deakin CD, Donnino MW, Drennan IR, Granfeldt A, Hoedemaekers CWE, Holmberg MJ, Hsu CH, Kamps M, Musiol S, Nation KJ, Neumar RW, Nicholson T, O'Neil BJ, Otto Q, de Paiva EF, Parr MJA, Reynolds JC, Sandroni C, Scholefield BR, Skrifvars MB, Wang TL, Wetsch WA, Yeung J, Morley PT, Morrison LJ, Welsford M, Hazinski MF, Nolan JP; Adult Advanced Life Support Collaborators. Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation. 2020 Nov;156:A80-A119. doi: 10.1016/j.resuscitation.2020.09.012. Epub 2020 Oct 21. — View Citation

Tagami T, Matsui H, Tanaka C, Kaneko J, Kuno M, Ishinokami S, Unemoto K, Fushimi K, Yasunaga H. Amiodarone Compared with Lidocaine for Out-Of-Hospital Cardiac Arrest with Refractory Ventricular Fibrillation on Hospital Arrival: a Nationwide Database Study. Cardiovasc Drugs Ther. 2016 Oct;30(5):485-491. doi: 10.1007/s10557-016-6689-7. — View Citation

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Zhao H, Fan K, Feng G. Amiodarone and/or lidocaine for cardiac arrest: A Bayesian network meta-analysis. Am J Emerg Med. 2020 Oct;38(10):2185-2193. doi: 10.1016/j.ajem.2020.06.074. Epub 2020 Jul 5. — View Citation

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Zipes DP, Prystowsky EN, Heger JJ. Amiodarone: electrophysiologic actions, pharmacokinetics and clinical effects. J Am Coll Cardiol. 1984 Apr;3(4):1059-71. doi: 10.1016/s0735-1097(84)80367-8. — View Citation

* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AMSA values	to determine whether AMSA values in the Amiodarone group are lower than in the NO Amiodarone gorup	through study completion, an average of 1 year
Secondary	Successful defibrilaltion	to assess the rate of successful defibrillation in the Amiodarone and in the NO Amiodarone group	through study completion, an average of 1 year
Secondary	ROSC	to assess the rate of ROSC in the Amiodarone and in the NO Amiodarone group	through study completion, an average of 1 year
Secondary	Survived event	to assess the rate of "survived event" in the Amiodarone and in the NO Amiodarone group	through study completion, an average of 1 year
Secondary	Survival to hospital discharge	to assess the rate of survival to hospital discharge in the Amiodarone and in the NO Amiodarone group	through study completion, an average of 1 year
Secondary	Prediction	to verify if AMSA maintain its predictive role for defibrillation success and ROSC also in the Amiodarone group	through study completion, an average of 1 year