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

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT01401647
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Canadian Institutes of Health Research (CIHR) (Other), Heart and Stroke Foundation of Canada (Other), American Heart Association (Other), Defence Research and Development Canada (Industry), U.S. Army Medical Research and Development Command (U.S. Fed)
• Enrollment: 3,024
• Locations: 9
• Arms: 3
• Duration (Months): 44
• Patients Per Site: 336
• Patients Per Site Per Month: 7.6

Study Details

Study Description

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

• Study Type: Interventional
• 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 1, 2012
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

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 Names: 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 Names: 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

Primary Outcome Measures

1. Number of Participants Who Survive From the Time of Cardiac Arrest to Hospital Discharge [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 [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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Alabama Resuscitation Center	Birmingham	Alabama	United States	35294
2	UCSD-San Diego Resuscitation Center	San Diego	California	United States	92103
3	Portland Resuscitation Outcomes Consortium, Oregon Health & Sciences University	Portland	Oregon	United States	97239
4	The Pittsburgh Resuscitation Network, University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15261
5	Dallas Center for Resuscitation Research, University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
6	Seattle-King County Center for Resuscitation Research, University of Washington	Seattle	Washington	United States	98195
7	Milwaukee Resuscitation Network, Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
8	University of Ottawa/University of British Columbia Collaborative RCC, Ottawa Health Research	Ottawa	Ontario	Canada
9	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 Development Command

Investigators

• Study Chair: Myron Weisfeldt, MD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• ROC Public Homepage

Publications

None provided.

• Responsible Party: Susanne May, Associate Professor, Biostatistics, University of Washington
• ClinicalTrials.gov Identifier: NCT01401647
• Other Study ID Numbers: 40605-D; 5U01HL077863-07
• First Posted: Jul 25, 2011
• Last Update Posted: Apr 17, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Susanne May, Associate Professor, Biostatistics, 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; Out-of-Hospital Cardiac Arrest; Ventricular Fibrillation; Lidocaine; Amiodarone

Study Results

Participant Flow

Arm/Group Title	Amiodarone	Lidocaine	Normal Saline
Arm/Group Description	Intravenous (IV) or intraosseous (IO) administration of amiodarone if VF/pulseless VT reoccurs after initial defibrillation. 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.	IV or IO administration of lidocaine if VF/pulseless VT reoccurs after initial defibrillation. 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.	IV or IO administration of normal saline if VF/pulseless VT reoccurs after initial defibrillation. 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.
Period Title: Overall Study
STARTED	972	993	1059
COMPLETED	968	985	1056
NOT COMPLETED	4	8	3

Baseline Characteristics

Arm/Group Title	Amiodarone	Lidocaine	Normal Saline	Total
Arm/Group Description	Intravenous (IV) or intraosseous (IO) administration of amiodarone if VF/pulseless VT reoccurs after initial defibrillation. 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.	IV or IO administration of lidocaine if VF/pulseless VT reoccurs after initial defibrillation. 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.	IV or IO administration of normal saline if VF/pulseless VT reoccurs after initial defibrillation. 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.	Total of all reporting groups
Overall Participants	972	993	1059	3024
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (14.0)	63.4 (14.7)	63.1 (14.6)	63.5 (14.4)
Sex: Female, Male (Count of Participants)
Female	211 21.7%	177 17.8%	215 20.3%	603 19.9%
Male	761 78.3%	816 82.2%	844 79.7%	2421 80.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	4 0.4%	2 0.2%	4 0.4%	10 0.3%
Asian	18 1.9%	17 1.7%	25 2.4%	60 2%
Native Hawaiian or Other Pacific Islander	3 0.3%	4 0.4%	5 0.5%	12 0.4%
Black or African American	95 9.8%	96 9.7%	97 9.2%	288 9.5%
White	334 34.4%	315 31.7%	340 32.1%	989 32.7%
More than one race	0 0%	0 0%	1 0.1%	1 0%
Unknown or Not Reported	518 53.3%	559 56.3%	587 55.4%	1664 55%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Survive From the Time of Cardiac Arrest to Hospital Discharge
Description	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.
Time Frame	Patients will be followed from the time of the cardiac arrest until death, hospital discharge, or December 31, 2015, whichever occurs first.

Outcome Measure Data

Analysis Population Description

The primary objective is to determine if survival to hospital discharge is improved with early therapeutic administration of IV amiodarone (PM101) compared to placebo.The secondary objectives of the trial are to determine if survival to hospital discharge is improved with early therapeutic administration of Lidocaine vs placebo; PM101 vs lidocaine.

Arm/Group Title	Amiodarone	Lidocaine	Normal Saline
Arm/Group Description	Intravenous (IV) or intraosseous (IO) administration of amiodarone if VF/pulseless VT reoccurs after initial defibrillation. 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.	IV or IO administration of lidocaine if VF/pulseless VT reoccurs after initial defibrillation. 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.	IV or IO administration of normal saline if VF/pulseless VT reoccurs after initial defibrillation. 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.
Measure Participants	968	985	1056
Number [participants]	237 24.4%	233 23.5%	222 21%

2. Secondary Outcome

Title	Number of Participants Scoring at or Below a 3 on the MRS Scale
Description	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
Time Frame	Patients will be followed from the time of the cardiac arrest until death, hospital discharge, or December 31, 2015, whichever occurs first.

Outcome Measure Data

Analysis Population Description

MRS as a secondary outcome is not available on all patients that we have survival for.

Arm/Group Title	Amiodarone	Lidocaine	Normal Saline
Arm/Group Description	Intravenous (IV) or intraosseous (IO) administration of amiodarone if VF/pulseless VT reoccurs after initial defibrillation. 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.	IV or IO administration of lidocaine if VF/pulseless VT reoccurs after initial defibrillation. 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.	IV or IO administration of normal saline if VF/pulseless VT reoccurs after initial defibrillation. 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.
Measure Participants	965	984	1055
Count of Participants [Participants]	182 18.7%	172 17.3%	175 16.5%

Adverse Events

Time Frame	Adverse event data were collected from the time a participating agency arrived on scene and up to 24 hours after Emergency Department arrival this results in adverse events reporting for up to 2 days.
Adverse Event Reporting Description	The following are commonly observed in patients who experience cardiac arrest or resuscitative efforts, and may or may not be attributable to specific resuscitation therapies. These were monitored and reported but not considered as adverse events of the study intervention. These include, but not limited to: pulmonary edema, airway bleeding, death, Clinical diagnoses of pneumonia, sepsis, cerebral bleeding, stroke, seizures, rearrest, serious rib fractures, and sternal fractures.
Arm/Group Title	Amiodarone		Lidocaine		Normal Saline
Arm/Group Description	Intravenous (IV) or intraosseous (IO) administration of amiodarone if VF/pulseless VT reoccurs after initial defibrillation. 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.		IV or IO administration of lidocaine if VF/pulseless VT reoccurs after initial defibrillation. 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.		IV or IO administration of normal saline if VF/pulseless VT reoccurs after initial defibrillation. 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.
All Cause Mortality
	Amiodarone		Lidocaine		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Amiodarone		Lidocaine		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/972 (0%)		0/993 (0%)		0/1059 (0%)
Other (Not Including Serious) Adverse Events
	Amiodarone		Lidocaine		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	515/972 (53%)		548/993 (55.2%)		476/1059 (44.9%)
Cardiac disorders
Hypotension requiring vasopressors	118/972 (12.1%)		114/993 (11.5%)		102/1059 (9.6%)
Rearrest	57/972 (5.9%)		76/993 (7.7%)		60/1059 (5.7%)
Nervous system disorders
Seizures or potential seizures	35/972 (3.6%)		49/993 (4.9%)		32/1059 (3%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Edema	202/972 (20.8%)		209/993 (21%)		184/1059 (17.4%)
Pneumonia	103/972 (10.6%)		100/993 (10.1%)		98/1059 (9.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.