Amiodarone, Lidocaine or Neither for Out-Of-Hospital Cardiac Arrest Due to Ventricular Fibrillation or Tachycardia (ALPS)

Study Description

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Brief Summary:

The primary objective of the trial is to determine if survival to hospital discharge is improved with early therapeutic administration of a new Captisol-Enabled formulation of IV amiodarone (Nexterone-PM101) compared to placebo.

Condition or disease	Intervention/treatment	Phase
Cardiac Arrest	Drug: amiodarone; Drug: Lidocaine; Other: Normal saline	Phase 3

Detailed Description:

The primary objective of the trial is to determine if survival to hospital discharge is improved with early therapeutic administration of a new Captisol-Enabled formulation of IV amiodarone (PM101) compared to placebo.

The corresponding null hypothesis is that survival to hospital discharge is identically distributed when out-of-hospital VF/VT arrest is treated with PM101 or placebo.

The secondary objectives of the trial are to determine if survival to hospital discharge is improved with early therapeutic administration of:

1. Lidocaine compared to placebo
2. PM101 compared to lidocaine The corresponding null hypotheses are that survival to hospital admission is identically distributed when out-of-hospital VF/VT arrest is treated with lidocaine as compared with placebo, and with PM101 as compared with lidocaine.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	3024 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Amiodarone, Lidocaine or Neither for Out-Of-Hospital Cardiac Arrest Due to Ventricular Fibrillation (VF) or Ventricular Tachycardia (VT)
Study Start Date :	May 2012
Actual Primary Completion Date :	December 2015
Actual Study Completion Date :	January 2016

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Amiodarone; Intravenous (IV) or intraosseous (IO) administration of amiodarone if VF/pulseless VT reoccurs after initial defibrillation.	Drug: amiodarone; 300 mg will be given IV/IO push for reoccurrence of ventricular fibrillation or pulseless ventricular tachycardia after 1 or more shocks. A second dose of 150 mg will be given if VF/pulseless VT reoccurs after initial dose and a subsequent shock. The initial dose for patients estimated to be less than 100 pounds will be 150 mg, followed by a second dose of 150 mg if the VF/pulseless VT persists.; Other Name: PM 101, Nexterone
Active Comparator: Lidocaine; IV or IO administration of lidocaine if VF/pulseless VT reoccurs after initial defibrillation.	Drug: Lidocaine; 120 mg will be given IV/IO push with reoccurrence of ventricular fibrillation or pulseless ventricular tachycardia after 1 or more shocks. A second dose of 60 mg will be given if VF/pulseless VT reoccurs after initial dose and a subsequent shock. The initial dose for patients estimated to be less than 100 pounds will be 60 mg, followed by a second dose of 60 mg if the VF/pulseless VT persists.; Other Name: lidocaine hydrochloride
Placebo Comparator: Normal saline; IV or IO administration of normal saline if VF/pulseless VT reoccurs after initial defibrillation.	Other: Normal saline; 6 cc of normal saline (NS) will be given IV/IO push for reoccurrence of ventricular fibrillation or pulseless ventricular tachycardia after 1 or more shocks. A second dose of 3 cc will be given if VF/pulseless VT reoccurs after initial dose and a subsequent shock. The initial dose for patients estimated to be less than 100 pounds will be 3 cc, followed by a second dose of 3 cc if the VF/pulseless VT persists.

Outcome Measures

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Primary Outcome Measures :

1. Number of Participants Who Survive From the Time of Cardiac Arrest to Hospital Discharge [ Time Frame: Patients will be followed from the time of the cardiac arrest until death, hospital discharge, or December 31, 2015, whichever occurs first. ]
   Patients may die in the field (outside of the hospital at the time of the cardiac arrest), at the emergency room, in the hospital, or they are discharged alive from the hospital.

Secondary Outcome Measures :

1. Number of Participants Scoring at or Below a 3 on the MRS Scale [ Time Frame: Patients will be followed from the time of the cardiac arrest until death, hospital discharge, or December 31, 2015, whichever occurs first. ]
   Neurologic status at discharge will be assessed using the modified Rankin Score (MRS). A higher value indicates a worse outcome. 0-No symptoms at all; 1-No significant disability despite symptoms; able to carry out all usual duties and activities, 2-Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance, 3-Moderate disability; requiring some help, but able to walk without assistance; 4-Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance, 5-Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6-Dead

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Age at least 18 years or local age of consent
• Non-traumatic out-of-hospital cardiac arrest treated by Resuscitation Outcomes Consortium (ROC) emergency medical services (EMS) with advanced life support capability
• VF or pulseless VT presenting as the initial arrest arrhythmia or results from conversion of another arrhythmia (such as transient asystole or pulseless electrical activity)
• Incessant or recurrent VF/VT after receipt of ≥ 1 shocks
• Established vascular access

Exclusion Criteria:

• Asystole or pulseless electrical activity (PEA) as the initial arrest rhythm who never transition to VF or pulseless VT
• Written advance directive to not attempt resuscitation (DNAR)
• Blunt, penetrating, or burn-related injury
• Exsanguination
• Protected populations (prisoners, pregnancy, children under local age of consent)
• Treated exclusively by non-ROC EMS agency/provider, or by basic life support-only capable ROC EMS providers
• Prior receipt of open label lidocaine or amiodarone during resuscitation

Contacts and Locations

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Locations

United States, Alabama
Alabama Resuscitation Center
Birmingham, Alabama, United States, 35294
United States, California
UCSD-San Diego Resuscitation Center
San Diego, California, United States, 92103
United States, Oregon
Portland Resuscitation Outcomes Consortium, Oregon Health & Sciences University
Portland, Oregon, United States, 97239
United States, Pennsylvania
The Pittsburgh Resuscitation Network, University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15261
United States, Texas
Dallas Center for Resuscitation Research, University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Washington
Seattle-King County Center for Resuscitation Research, University of Washington
Seattle, Washington, United States, 98195
United States, Wisconsin
Milwaukee Resuscitation Network, Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Ontario
University of Ottawa/University of British Columbia Collaborative RCC, Ottawa Health Research
Ottawa, Ontario, Canada
Toronto Regional Resuscitation Research Out-of-Hospital Network, University of Toronto
Toronto, Ontario, Canada

Sponsors and Collaborators

University of Washington

National Heart, Lung, and Blood Institute (NHLBI)

Canadian Institutes of Health Research (CIHR)

Heart and Stroke Foundation of Canada

American Heart Association

Defence Research and Development Canada

U.S. Army Medical Research and Materiel Command

Investigators

Study Chair:	Myron Weisfeldt, MD	Johns Hopkins University

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

ROC Public Homepage 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, Leroux B, Vaillancourt C, Wittwer L, Callaway CW, Christenson J, Egan D, Ornato JP, Weisfeldt ML, Stiell IG, Idris AH, Aufderheide TP, Dunford JV, Colella MR, Vilke GM, Brienza AM, Desvigne-Nickens P, Gray PC, Gray R, Seals N, Straight R, Dorian P; Resuscitation Outcomes Consortium Investigators. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2016 May 5;374(18):1711-22. doi: 10.1056/NEJMoa1514204. Epub 2016 Apr 4.

Responsible Party:	Susanne May, Associate Professor, Biostatistics, University of Washington
ClinicalTrials.gov Identifier:	NCT01401647 History of Changes
Other Study ID Numbers:	40605-D; 5U01HL077863-07 ( U.S. NIH Grant/Contract )
First Posted:	July 25, 2011
Results First Posted:	January 30, 2017
Last Update Posted:	April 17, 2017
Last Verified:	March 2017

Keywords provided by Susanne May, University of Washington:

cardiac arrest; cardiopulmonary resuscitation; ventricular fibrillation; pulseless ventricular tachycardia; Non-traumatic Out of Hospital Cardiac Arrest (OOHCA)

Additional relevant MeSH terms:

Heart Arrest; Tachycardia; Tachycardia, Ventricular; Out-of-Hospital Cardiac Arrest; Ventricular Fibrillation; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Pathologic Processes; Lidocaine; Amiodarone; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs

Sensory System Agents; Peripheral Nervous System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Potassium Channel Blockers; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP3A Inhibitors