Cardiac Arrest, Cardiopulmonary Resuscitation, Death, Sudden, Cardiac, Heart Arrest
Conditions
Keywords
Heart Arrest, Cardiac Arrest, Cardiopulmonary Resuscitation, Impedance Threshold Device, Active Compression Decompression, ResQPOD, ResQPump, Survival, Out-of-hospital, Prehospital, ResQCPR System
Brief summary
The purpose of this study is to determine whether performing active compression decompression cardiopulmonary resuscitation (ACD-CPR) with an impedance threshold device (ITD) compared to conventional standard cardiopulmonary resuscitation (S-CPR) will impact the neurologic recovery and survival to hospital discharge following out-of-hospital cardiac arrest.
Detailed description
Despite receiving conventional, standard CPR (S-CPR), most patients who experience out-of-hospital cardiac arrest die prior to arriving at a hospital. At the present time, the hospital discharge rate following out-of-hospital, nontraumatic cardiac arrest in adults in the United States is estimated to be less than 5%. Many factors contribute to the current poor survival statistics, including the inefficiency of the technique itself. CPR provides only 10% to 20% of normal myocardial perfusion, and only 20% to 30% of physiologically normal cerebral perfusion. A new method of CPR that combines ACD and an ITD (ACD-CPR+ITD) has been shown in animal models and in clinical trials conducted in Europe to provide significantly more blood flow to the vital organs and to improve survival rates when compared to S-CPR or ACD-CPR alone. ACD-CPR+ITD works by decreasing intrathoracic pressure during the chest wall recoil (or decompression) phase of CPR, creating a vacuum within the thorax relative to the rest of the body. When compared with controls, use of ACD-CPR+ITD (a) enhances blood return to the thorax during the chest wall recoil phase, (b) enhances blood flow to the heart and brain, (c) provides real-time feedback to rescuers to maintain high-quality CPR, (d) improves overall CPR efficiency and, as a result of the forgoing, (e) improves short-term survival rates. The sponsor and others recently evaluated the effectiveness of the combination of conventional, manual standard CPR±ITD in animals and humans. The ITD increased short-term survival rates in these studies as well. Two clinical trials were performed in Milwaukee, Wisconsin, under IDE (#G980125). Both compared S-CPR with either a sham (nonfunctional or placebo) or active (functional) ITD. The results from the hemodynamic study demonstrated that systolic blood pressure, the primary end point, increased from approximately 45 mmHg with the sham ITD to approximately 85 mmHg with the active ITD (P less than 0.05). Intensive care unit admission rate was the primary end point of the clinical outcome study. Comparisons: The objective of this two-arm, multisite, randomized, pivotal IDE clinical trial is to compare survival to hospital discharge with neurologic recovery rates in subjects receiving S-CPR compared to ACD-CPR+ITD following out-of-hospital cardiac arrest in well-established American emergency medical services systems.
Interventions
DEVICEUse of an impedance threshold device (ITD) during the performance of active compression decompression CPR (ACD-CPR)
The ITD selectively prevents the influx of unnecessary respiratory gases into the patient during the chest wall recoil phase of CPR. The ResQPump, a hand-held device containing a suction cup, attaches to the chest and actively compresses and actively re-expands the chest during the performance of CPR.
PROCEDUREStandard cardiopulmonary resuscitation (S-CPR)
Conventional standard cardiopulmonary resuscitation (S-CPR)
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Advanced Circulatory Systems
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult subjects initially presumed or known to be 18 years of age or older * Subjects who present with out-of-hospital cardiac arrest from presumed cardiac etiology and who receive CPR by Emergency Medical Services (EMS) personnel for at least 1 minute * Subjects whose airways are managed with a cuffed ET tube, combitube, or laryngeal mask airway or facemask
Exclusion criteria
* Adult subjects presumed or known to be less than 18 years of age * Subjects with known or likely traumatic injuries causing cardiac arrest or cardiac arrest of presumed noncardiac origin * Subjects with preexisting Do Not Resuscitate (DNR) orders * Subjects with signs of obvious clinical death or conditions that preclude the use of CPR * Family or legal representative request that the subject not be entered into the study * Subjects experiencing in-hospital cardiac arrest * Subjects with a recent sternotomy with wound not appearing completely healed (if unknown) or less than 6 months (if known) * Subjects who received less than 1 minute of CPR by EMS personnel * Subjects with a complete airway obstruction that cannot be cleared or in whom attempts at advanced airway management are unsuccessful * Subjects intubated with a leaky or uncuffed advanced airway device or presence of stomas, tracheotomies, or tracheostomies * Subjects who rearrest and are encountered by EMS within 365 days of the index cardiac arrest
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Survived to Hospital Discharge With Favorable Neurologic Function Defined as MRS Score <=3 | When the subject is discharged from the hospital; an average of 12 days after cardiac arrest for subjects surviving to hospital discharge | favorable neurologic function is defined as modified Rankin Scale (MRS) score \<= 3. Modified Rankin Scale measures functional outcome in stroke. It is a scale of 0-5 where 0=no symptoms at all and 5=severe disability: bedridden, incontinent, and requiring constant nursing care and attention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Adverse Event Rate as Measured by Number of Patients With One or More Adverse Events | Time from cardiac arrest through hospital discharge (an average of 12 days for subjects surviving to hospital discharge | Number of patients with one or more major adverse events, through hospital discharge. Major adverse events included: death, rearrest, pulmonary edema, seizure, bleeding requiring intervention, rib/sterna fracture, pneumothorax, hemothorax, cardiac tamponade, cerebral bleeding, aspiration, internal organ injury. |
| Return of Spontaneous Circulation (ROSC) | Time of cardiac arrest until discontinuation of efforts | Number of subjects who had ROSC, defined as any return of spontaneous circulation for any duration, reported during resuscitation in the field by EMS. |
| Survival to Hospital (e.g., Intensive Care Unit) Admission | Time of hospital admission, up to 1 day after cardiac arrest | Number of patients who survived to hospital or ICU admission after being transported to the emergency department (ED) after out-of-hospital cardiac arrest. |
| Survival to 24 Hours | 24 hours following cardiac arrest | Number of patients who were alive 24 hours after the initial cardiac arrest. |
| Survival to Hospital Discharge | cardiac arrest to hospital discharge | — |
| Survival to 90 Days | 90 days following cardiac arrest | Number of patients who are known to be alive 90 days after the index cardiac arrest. |
| Survival to 365 Days | 365 days following cardiac arrest | Number of patients who are alive 365 days after the index cardiac arrest. |
| Neurological Recovery at 1 Year [Measured by Cognitive Abilities Screening Instrument (CASI)] | One year after index arrest | CASI is scored on a scale of 0-100 with 100 being the best score. The instrument evaluates attention, concentration, and short- and long-term memory as well as language and abstraction. The CASI score is a total score and not an aggregate of subscores. |
Countries
United States
Participant flow
Recruitment details
The study was conducted under a waiver of informed consent for emergency research that was approved by the U.S. Food and Drug Administration and by the Institutional Review Boards at participating study sites. All adults with out-of-hospital cardiac arrest were eligible for the study.
Pre-assignment details
All sites were required to complete a run-in phase prior to to beginning randomization. A total of 2667 patients (197 run-in, 2470 pivotal) were provisionally enrolled and received randomized CPR treatment. Of these, 1653 pivotal patients met the final selection criteria (non-traumatic arrest due to cardiac cause).
Participants by arm
| Arm | Count |
|---|---|
| Standard CPR Conventional standard cardiopulmonary resuscitation (S-CPR) | 813 |
| ACD CPR Plus ITD Active compression decompression CPR plus an Impedance Threshold Device | 840 |
| Total | 1,653 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 746 | 747 |
| Overall Study | Lost to Follow-up | 10 | 10 |
| Overall Study | Withdrawal by Subject | 9 | 9 |
Baseline characteristics
| Characteristic | ACD CPR Plus ITD | Standard CPR | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 470 Participants | 436 Participants | 906 Participants |
| Age, Categorical Between 18 and 65 years | 369 Participants | 377 Participants | 746 Participants |
| Age, Continuous | 67.0 years STANDARD_DEVIATION 15.2 | 66.8 years STANDARD_DEVIATION 14.5 | 66.9 years STANDARD_DEVIATION 14.9 |
| Region of Enrollment United States | 840 participants | 813 participants | 1653 participants |
| Sex: Female, Male Female | 282 Participants | 274 Participants | 556 Participants |
| Sex: Female, Male Male | 558 Participants | 539 Participants | 1097 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 766 / 813 | 787 / 840 |
Outcome results
Primary
Number of Patients Who Survived to Hospital Discharge With Favorable Neurologic Function Defined as MRS Score <=3
favorable neurologic function is defined as modified Rankin Scale (MRS) score \<= 3. Modified Rankin Scale measures functional outcome in stroke. It is a scale of 0-5 where 0=no symptoms at all and 5=severe disability: bedridden, incontinent, and requiring constant nursing care and attention.
Time frame: When the subject is discharged from the hospital; an average of 12 days after cardiac arrest for subjects surviving to hospital discharge
Population: The population was a modified Intent to Treat (mITT) population who received EMS CPR per study protocol after meeting initial inclusion criteria and who were finally included in the final analysis population after meeting final inclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard CPR | Number of Patients Who Survived to Hospital Discharge With Favorable Neurologic Function Defined as MRS Score <=3 | 47 patients |
| ACD CPR Plus ITD | Number of Patients Who Survived to Hospital Discharge With Favorable Neurologic Function Defined as MRS Score <=3 | 75 patients |
p-value: 0.01995% CI: [1.07, 2.36]Fisher Exact
Secondary
Major Adverse Event Rate as Measured by Number of Patients With One or More Adverse Events
Number of patients with one or more major adverse events, through hospital discharge. Major adverse events included: death, rearrest, pulmonary edema, seizure, bleeding requiring intervention, rib/sterna fracture, pneumothorax, hemothorax, cardiac tamponade, cerebral bleeding, aspiration, internal organ injury.
Time frame: Time from cardiac arrest through hospital discharge (an average of 12 days for subjects surviving to hospital discharge
Population: Population is a modified Intent to Treat (mITT) population consisting of patients who met all initial and final inclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard CPR | Major Adverse Event Rate as Measured by Number of Patients With One or More Adverse Events | 766 patients |
| ACD CPR Plus ITD | Major Adverse Event Rate as Measured by Number of Patients With One or More Adverse Events | 787 patients |
p-value: 0.0001Fisher Exact test, for non-inferiority
p-value: 0.681Fisher Exact
Secondary
Neurological Recovery at 1 Year [Measured by Cognitive Abilities Screening Instrument (CASI)]
CASI is scored on a scale of 0-100 with 100 being the best score. The instrument evaluates attention, concentration, and short- and long-term memory as well as language and abstraction. The CASI score is a total score and not an aggregate of subscores.
Time frame: One year after index arrest
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard CPR | Neurological Recovery at 1 Year [Measured by Cognitive Abilities Screening Instrument (CASI)] | 93.7 units on a scale | Standard Deviation 11.8 |
| ACD CPR Plus ITD | Neurological Recovery at 1 Year [Measured by Cognitive Abilities Screening Instrument (CASI)] | 94.7 units on a scale | Standard Deviation 4.4 |
Secondary
Return of Spontaneous Circulation (ROSC)
Number of subjects who had ROSC, defined as any return of spontaneous circulation for any duration, reported during resuscitation in the field by EMS.
Time frame: Time of cardiac arrest until discontinuation of efforts
Population: Population was a modified Intent to Treat (mITT) population that consisted of patients who met all initial and final inclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard CPR | Return of Spontaneous Circulation (ROSC) | 324 patients |
| ACD CPR Plus ITD | Return of Spontaneous Circulation (ROSC) | 343 patients |
Secondary
Survival to 24 Hours
Number of patients who were alive 24 hours after the initial cardiac arrest.
Time frame: 24 hours following cardiac arrest
Population: Population is a modified Intent to Treat (mITT) population who met ititial inclusion criteria and final inclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard CPR | Survival to 24 Hours | 176 patients |
| ACD CPR Plus ITD | Survival to 24 Hours | 197 patients |
Secondary
Survival to 365 Days
Number of patients who are alive 365 days after the index cardiac arrest.
Time frame: 365 days following cardiac arrest
Population: Population is a modified Intent to Treat (mITT) population who met initial and final inclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard CPR | Survival to 365 Days | 48 patients |
| ACD CPR Plus ITD | Survival to 365 Days | 74 patients |
p-value: 0.024Fisher Exact
Secondary
Survival to 90 Days
Number of patients who are known to be alive 90 days after the index cardiac arrest.
Time frame: 90 days following cardiac arrest
Population: Population is a modified Intent to Treat (mITT) population that met initial and final inclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard CPR | Survival to 90 Days | 58 patients |
| ACD CPR Plus ITD | Survival to 90 Days | 87 patients |
Secondary
Survival to Hospital Discharge
Time frame: cardiac arrest to hospital discharge
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard CPR | Survival to Hospital Discharge | 104 patients |
| ACD CPR Plus ITD | Survival to Hospital Discharge | 80 patients |
Secondary
Survival to Hospital (e.g., Intensive Care Unit) Admission
Number of patients who survived to hospital or ICU admission after being transported to the emergency department (ED) after out-of-hospital cardiac arrest.
Time frame: Time of hospital admission, up to 1 day after cardiac arrest
Population: Population is a modified Intent to Treat (mITT) population who received EMS CPR per study protocol after meeting initial inclusion criteria and also met final inclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard CPR | Survival to Hospital (e.g., Intensive Care Unit) Admission | 216 patients |
| ACD CPR Plus ITD | Survival to Hospital (e.g., Intensive Care Unit) Admission | 237 patients |