Cardiac Arrest
Conditions
Keywords
cardiac arrest, cardiopulmonary resuscitation, ventricular fibrillation, pulseless ventricular tachycardia, Non-traumatic Out of Hospital Cardiac Arrest (OOHCA)
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.
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.
Interventions
DRUGamiodarone
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.
DRUGLidocaine
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.
OTHERNormal 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.
Sponsors
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
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Amiodarone 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. | 972 |
| Lidocaine 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. | 993 |
| Normal Saline 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. | 1,059 |
| Total | 3,024 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 5 | 2 |
Baseline characteristics
| Characteristic | Amiodarone | Lidocaine | Normal Saline | Total |
|---|---|---|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 14 | 63.4 years STANDARD_DEVIATION 14.7 | 63.1 years STANDARD_DEVIATION 14.6 | 63.5 years STANDARD_DEVIATION 14.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 2 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 17 Participants | 25 Participants | 60 Participants |
| Race (NIH/OMB) Black or African American | 95 Participants | 96 Participants | 97 Participants | 288 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 4 Participants | 5 Participants | 12 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 518 Participants | 559 Participants | 587 Participants | 1664 Participants |
| Race (NIH/OMB) White | 334 Participants | 315 Participants | 340 Participants | 989 Participants |
| Sex: Female, Male Female | 211 Participants | 177 Participants | 215 Participants | 603 Participants |
| Sex: Female, Male Male | 761 Participants | 816 Participants | 844 Participants | 2421 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 515 / 972 | 548 / 993 | 476 / 1,059 |
| serious Total, serious adverse events | 0 / 972 | 0 / 993 | 0 / 1,059 |
Outcome results
Primary
Number of Participants Who Survive From the Time of Cardiac Arrest to Hospital Discharge
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.
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Amiodarone | Number of Participants Who Survive From the Time of Cardiac Arrest to Hospital Discharge | 237 participants |
| Lidocaine | Number of Participants Who Survive From the Time of Cardiac Arrest to Hospital Discharge | 233 participants |
| Normal Saline | Number of Participants Who Survive From the Time of Cardiac Arrest to Hospital Discharge | 222 participants |
Secondary
Number of Participants Scoring at or Below a 3 on the MRS Scale
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.
Population: MRS as a secondary outcome is not available on all patients that we have survival for.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amiodarone | Number of Participants Scoring at or Below a 3 on the MRS Scale | 182 Participants |
| Lidocaine | Number of Participants Scoring at or Below a 3 on the MRS Scale | 172 Participants |
| Normal Saline | Number of Participants Scoring at or Below a 3 on the MRS Scale | 175 Participants |