Heart Arrest
Conditions
Keywords
cardiac arrest, cardiopulmonary resuscitation
Brief summary
The purpose of this study is to look at two different treatments during a cardiac arrest that occurs outside of the hospital and whether either or both treatments will increase the number of people who live to hospital discharge. A cardiac arrest is when the heart stops pumping blood to the body.
Detailed description
The first treatment involves using a device called the Impedance Threshold Device (ITD). The ITD is a small hard plastic device about the size of a fist that is attached to the face mask or airway tube used during CPR (cardiopulmonary resuscitation). The ITD provides increased blood flow back to the heart during chest compressions until the heart starts beating on its own again. The other treatment involves the amount of CPR given before the emergency medical services (EMS) providers first look at the heart rhythm to determine if a shock is needed. A person would receive either about 30 seconds of chest compressions or about 3 minutes of compressions before checking the heart rhythm. Giving some compressions before checking the heart rhythm increases the blood being circulated to the body. Researchers do not know how many compressions before the rhythm check are necessary to save more lives. Depending on the circumstances of the cardiac arrest a person may receive only one of these treatments or both of these treatments. The purpose of the research study is to determine if more people live when either the real ITD is used or if additional CPR is given before looking at the heart rhythm the first time. This study is being conducted in 9 different areas throughout the United States and Canada by the Resuscitation Outcomes Consortium (ROC). About 15,000 patients will be enrolled in this research study.
Interventions
Use of Impedance Threshold Device (ITD)
DEVICESham ITD
Sham ITD
OTHERAnalyze early
Upon EMS arrival at the scene of a non-traumatic cardiac arrest, an assessment of the cardiac rhythm is done to determine whether a defibrillatory shock is required.
OTHERAnalyze later
Upon EMS arrival at the scene of a non-traumatic cardiac arrest, three minutes of CPR is given prior to the assessment of the cardiac rhythm to determine whether a defibrillatory shock is required.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Neurological Disorders and Stroke (NINDS)
Canadian Institutes of Health Research (CIHR)
Defence Research and Development Canada
Heart and Stroke Foundation of Canada
American Heart Association
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All persons of local age of consent or older who suffer non-traumatic cardiopulmonary arrest outside of the hospital in the study communities with defibrillation and/or delivery of chest compressions provided by emergency medical service (EMS) providers dispatched to the scene and do not meet any of the
Exclusion criteria
.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival to Hospital Discharge With Satisfactory Function (Modified Rankin Scale [MRS] of Less Than or Equal to 3). | Hospital discharge or death prior to discharge | The modified Rankin Score (mRS) measures the ability of patients to function independently. The scale goes from 0 (no symptoms) to 6 (death). Subjects with a mRS scores of three or less (i.e. better) at the time of hospital discharge were considered to have a positive outcome, resulting in a binary measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival to Hospital Discharge | Survival to hospital discharge or death before discharge | — |
| Modified Rankin Score at 6 Months After Hospital Discharge | 6 months post hospital discharge | The modified Rankin Score (mRS) measures the ability of patients to function independently. The scale goes from 0 (no symptoms) to 6 (death). |
| Adult Lifestyle and Function Version of Mini-Mental Status Exam at 6 Months | 6 months post hospital discharge | The adult lifestyle and function interview (ALFI) version of the mini-mental status exam (MMSE) measures neurological status. The ALFI-MMSE has 23 items. It is scored from 0 to 22, with lower scores interpreted as being worse. |
| Health Utilities Index III Score and Geriatric Depression Scale Score 6 Months | 6 months post hospital discharge | The Health Utilities Index Mark 3 system was used to evaluate generic health related quality of life (HRQL). The interview-administered version of HUI3 requires completion of a maximum of 39 questions. The HUI3 consists of eight attributes of general health (vision, hearing, speech, mobility, dexterity, emotion, cognition, and pain) with five or six levels per attribute. For each respondent, health status is described as a vector that combines the levels of each attribute. This information is then converted into a utility score of HRQL on a scale from perfect health (1.0) to death (0). |
Countries
Canada, United States
Participant flow
Recruitment details
Clinical sites enrolled patients during a run-in period with the first patient enrolled on June 7, 2007. The run-in period ranged from from 2 to 6 months across the sites. The last patient was enrolled in the evaluable phase on November 6, 2009. All patients were enrolled in the pre-hospital EMS setting.
Participants by arm
| Arm | Count |
|---|---|
| Analyze Early + ITD Analyze early: upon EMS (emergency medical services) arrival at the scene of a non-traumatic cardiac arrest, the EMS providers assess the cardiac rhythm as soon as possible. Approximately thirty seconds of CPR (cardiopulmonary resuscitation) may be done prior to an assessment of the cardiac rhythm to determine whether a defibrillatory shock is required. Use of ITD (Impedance Threshold Device) by EMS providers in the prehospital setting. | 1,817 |
| Analyze Early + Sham Analyze early: upon EMS arrival at the scene of a non-traumatic cardiac arrest, the EMS providers assess the cardiac rhythm as soon as possible. Approximately thirty seconds of CPR may be done prior to an assessment of the cardiac rhythm to determine whether a defibrillatory shock is required. Use of a sham ITD by EMS providers in the pre-hospital setting. | 1,861 |
| Analyze Early, Not in ITD vs Sham Analyze early. Upon EMS arrival at the scene of a non-traumatic cardiac arrest, the EMS providers assess the cardiac rhythm as soon as possible. Approximately thirty seconds of CPR may be done prior to an assessment of the cardiac rhythm to determine whether a defibrillatory shock is required. Neither an ITD nor sham device used. | 1,621 |
| Analyze Later + ITD Analyze later: upon the EMS arrival at the scene of a non-traumatic cardiac arrest, three minutes of CPR is done prior to the assessment of the cardiac rhythm to determine whether a defibrillatory shock is required. Use of Impedance Threshold Device by EMS providers in the pre-hospital setting. | 1,631 |
| Analyze Later + Sham Analyze later: upon the EMS arrival at the scene of a non-traumatic cardiac arrest, three minutes of CPR is done prior to the assessment of the cardiac rhythm to determine whether a defibrillatory shock is required. Use of a sham ITD by EMS providers in the pre-hospital setting. | 1,633 |
| Analyze Later, Not in ITD vs. Sham Analyze later: upon the EMS arrival at the scene of a non-traumatic cardiac arrest, three minutes of CPR is done prior to the assessment of the cardiac rhythm to determine whether a defibrillatory shock is required. Neither an ITD nor sham device used. | 1,379 |
| Not in AEvAL, ITD Device Upon the EMS arrival at the scene of a non-traumatic cardiac arrest, local policy determines the length of CPR done prior to the assessment of the cardiac rhythm to determine whether a defibrillatory shock is required. Impedance Threshold Device used by EMS providers in the pre-hospital setting. | 929 |
| Not in AEvAL, Sham Upon the EMS arrival at the scene of a non-traumatic cardiac arrest, local policy determines the length of CPR done prior to the assessment of the cardiac rhythm to determine whether a defibrillatory shock is required. Sham ITD used by EMS providers in the pre-hospital setting. | 851 |
| Total | 11,722 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 2 | 8 | 1 | 2 | 5 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 | 0 | 0 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Analyze Early + Sham | Analyze Early, Not in ITD vs Sham | Analyze Later + ITD | Analyze Later + Sham | Analyze Later, Not in ITD vs. Sham | Analyze Early + ITD | Not in AEvAL, ITD Device | Not in AEvAL, Sham | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 2 Participants | 1 Participants | 4 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 11 Participants |
| Age, Categorical >=65 years | 1050 Participants | 932 Participants | 937 Participants | 954 Participants | 789 Participants | 1082 Participants | 547 Participants | 481 Participants | 6772 Participants |
| Age, Categorical Between 18 and 65 years | 809 Participants | 687 Participants | 693 Participants | 675 Participants | 590 Participants | 734 Participants | 381 Participants | 370 Participants | 4939 Participants |
| Age, Continuous | 66.6 years STANDARD_DEVIATION 16.4 | 66.3 years STANDARD_DEVIATION 17 | 67.2 years STANDARD_DEVIATION 16.6 | 67.1 years STANDARD_DEVIATION 16.4 | 66.3 years STANDARD_DEVIATION 16.7 | 67.3 years STANDARD_DEVIATION 16.3 | 67.7 years STANDARD_DEVIATION 16.3 | 66.7 years STANDARD_DEVIATION 16.7 | 66.9 years STANDARD_DEVIATION 16.6 |
| Region of Enrollment Canada | 1097 participants | 1210 participants | 940 participants | 935 participants | 979 participants | 1084 participants | 395 participants | 362 participants | 7002 participants |
| Region of Enrollment United States | 764 participants | 411 participants | 691 participants | 698 participants | 400 participants | 733 participants | 534 participants | 489 participants | 4720 participants |
| Sex: Female, Male Female | 673 Participants | 605 Participants | 615 Participants | 578 Participants | 486 Participants | 609 Participants | 313 Participants | 303 Participants | 4182 Participants |
| Sex: Female, Male Male | 1188 Participants | 1016 Participants | 1016 Participants | 1055 Participants | 893 Participants | 1208 Participants | 616 Participants | 548 Participants | 7540 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 2,310 | 0 / 2,321 | 0 / 2,051 | 0 / 2,156 | 0 / 2,191 | 0 / 1,839 | 0 / 1,336 | 0 / 1,278 |
| serious Total, serious adverse events | 154 / 2,310 | 193 / 2,321 | 122 / 2,051 | 166 / 2,156 | 174 / 2,191 | 121 / 1,839 | 181 / 1,336 | 152 / 1,278 |
Outcome results
Primary
Survival to Hospital Discharge With Satisfactory Function (Modified Rankin Scale [MRS] of Less Than or Equal to 3).
The modified Rankin Score (mRS) measures the ability of patients to function independently. The scale goes from 0 (no symptoms) to 6 (death). Subjects with a mRS scores of three or less (i.e. better) at the time of hospital discharge were considered to have a positive outcome, resulting in a binary measure.
Time frame: Hospital discharge or death prior to discharge
Population: Analyses of both interventions excluded subjects who suffered arrest secondary to drowning, strangulation, or electrocution; or for whom the primary outcome was unknown. Additionally, the ITD vs. Sham analysis excluded subjects who did not have the device applied, had study exclusions, or who had a response time of more than 15 minutes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Analyze Early | Survival to Hospital Discharge With Satisfactory Function (Modified Rankin Scale [MRS] of Less Than or Equal to 3). | 310 participants |
| Analyze Later | Survival to Hospital Discharge With Satisfactory Function (Modified Rankin Scale [MRS] of Less Than or Equal to 3). | 273 participants |
| Active ITD | Survival to Hospital Discharge With Satisfactory Function (Modified Rankin Scale [MRS] of Less Than or Equal to 3). | 254 participants |
| Sham ITD | Survival to Hospital Discharge With Satisfactory Function (Modified Rankin Scale [MRS] of Less Than or Equal to 3). | 260 participants |
Comparison: Comparison of the rates of MRS \<=3 in Analyze Early vs. Analyze Later arms using a linear mixed effect model with an identity link and random effects to account for the cluster randomization.p-value: 0.5995% CI: [-1.1, 0.7]Mixed Models Analysis
Comparison: Comparison of the rates of MRS \<=3 in Active ITD and Sham treatment arms, adjusted for sequential monitoring.p-value: 0.7195% CI: [-1.1, 0.8]t-test, 2 sided
Secondary
Adult Lifestyle and Function Version of Mini-Mental Status Exam at 6 Months
The adult lifestyle and function interview (ALFI) version of the mini-mental status exam (MMSE) measures neurological status. The ALFI-MMSE has 23 items. It is scored from 0 to 22, with lower scores interpreted as being worse.
Time frame: 6 months post hospital discharge
Population: ITT population, survived to hospital discharge, consented to participate in the post-discharge substudy, and with at least one post-discharge assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Analyze Early | Adult Lifestyle and Function Version of Mini-Mental Status Exam at 6 Months | 18.3 units on a scale | Standard Deviation 6 |
| Analyze Later | Adult Lifestyle and Function Version of Mini-Mental Status Exam at 6 Months | 18.5 units on a scale | Standard Deviation 5.5 |
| Active ITD | Adult Lifestyle and Function Version of Mini-Mental Status Exam at 6 Months | 18.0 units on a scale | Standard Deviation 6.3 |
| Sham ITD | Adult Lifestyle and Function Version of Mini-Mental Status Exam at 6 Months | 18.7 units on a scale | Standard Deviation 5.5 |
Comparison: Linear regression was used to assess associations between post-discharge measures and treatment group comparisons with adjustment for baseline characteristics. Site was adjusted for to accommodate clustering of patients within sites. All regression analyses used robust standard errors to accommodate non-constant variances.95% CI: [-0.71, 0.83]
Comparison: Linear regression was used to assess associations between post-discharge measures and treatment group comparisons with adjustment for baseline characteristics. Site was adjusted for to accommodate clustering of patients within sites. All regression analyses used robust standard errors to accommodate non-constant variances.95% CI: [-1.61, 0.28]
Secondary
Health Utilities Index III Score and Geriatric Depression Scale Score 6 Months
The Health Utilities Index Mark 3 system was used to evaluate generic health related quality of life (HRQL). The interview-administered version of HUI3 requires completion of a maximum of 39 questions. The HUI3 consists of eight attributes of general health (vision, hearing, speech, mobility, dexterity, emotion, cognition, and pain) with five or six levels per attribute. For each respondent, health status is described as a vector that combines the levels of each attribute. This information is then converted into a utility score of HRQL on a scale from perfect health (1.0) to death (0).
Time frame: 6 months post hospital discharge
Population: ITT population, survived to hospital discharge, consented to participate in the post-discharge substudy, and with at least one post-discharge assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Analyze Early | Health Utilities Index III Score and Geriatric Depression Scale Score 6 Months | 0.74 units on a scale | Standard Deviation 0.34 |
| Analyze Later | Health Utilities Index III Score and Geriatric Depression Scale Score 6 Months | 0.73 units on a scale | Standard Deviation 0.35 |
| Active ITD | Health Utilities Index III Score and Geriatric Depression Scale Score 6 Months | 0.71 units on a scale | Standard Deviation 0.36 |
| Sham ITD | Health Utilities Index III Score and Geriatric Depression Scale Score 6 Months | 0.75 units on a scale | Standard Deviation 0.33 |
Comparison: Linear regression was used to assess associations between post-discharge measures and treatment group comparisons with adjustment for baseline characteristics. Site was adjusted for to accommodate clustering of patients within sites. All regression analyses used robust standard errors to accommodate non-constant variances.95% CI: [-0.06, 0.05]
Comparison: Linear regression was used to assess associations between post-discharge measures and treatment group comparisons with adjustment for baseline characteristics. Site was adjusted for to accommodate clustering of patients within sites. All regression analyses used robust standard errors to accommodate non-constant variances.95% CI: [-0.08, 0.05]
Secondary
Modified Rankin Score at 6 Months After Hospital Discharge
The modified Rankin Score (mRS) measures the ability of patients to function independently. The scale goes from 0 (no symptoms) to 6 (death).
Time frame: 6 months post hospital discharge
Population: ITT population, survived to hospital discharge, consented to participate in the post-discharge substudy, and with at least one post-discharge assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Analyze Early | Modified Rankin Score at 6 Months After Hospital Discharge | 1.7 units on a scale | Standard Deviation 1.8 |
| Analyze Later | Modified Rankin Score at 6 Months After Hospital Discharge | 1.8 units on a scale | Standard Deviation 1.8 |
| Active ITD | Modified Rankin Score at 6 Months After Hospital Discharge | 1.8 units on a scale | Standard Deviation 1.9 |
| Sham ITD | Modified Rankin Score at 6 Months After Hospital Discharge | 1.6 units on a scale | Standard Deviation 1.7 |
Comparison: Linear regression was used to assess associations between post-discharge measures and treatment group comparisons with adjustment for baseline characteristics. Site was adjusted for to accommodate clustering of patients within sites. All regression analyses used robust standard errors to accommodate non-constant variances.95% CI: [-0.2, 0.34]
Comparison: Linear regression was used to assess associations between post-discharge measures and treatment group comparisons with adjustment for baseline characteristics. Site was adjusted for to accommodate clustering of patients within sites. All regression analyses used robust standard errors to accommodate non-constant variances.95% CI: [-0.17, 0.44]
Secondary
Survival to Hospital Discharge
Time frame: Survival to hospital discharge or death before discharge
Population: Analyses of both interventions excluded subjects who suffered arrest secondary to drowning, strangulation, or electrocution; or for whom the primary outcome was unknown. Additionally, the ITD vs. Sham analysis excluded subjects who did not have the device applied, had study exclusions, or who had a response time of more than 15 minutes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Analyze Early | Survival to Hospital Discharge | 427 participants |
| Analyze Later | Survival to Hospital Discharge | 372 participants |
| Active ITD | Survival to Hospital Discharge | 357 participants |
| Sham ITD | Survival to Hospital Discharge | 355 participants |
Comparison: Comparison of the rates of survival to hospital discharge in Analyze Early vs. Analyze Later arms using a generalized estimating equations model with an identity link, grouping on cluster.p-value: 0.9295% CI: [-1.2, 1.1]GEE
Comparison: Comparison of the rates of survival to hospital discharge in Active ITD and Sham treatment arms.p-value: 0.9995% CI: [-1.2, 1.1]t-test, 2 sided