Cardiac Arrest
Conditions
Keywords
Cardiac Arrest, Pre-hospital, Mild hypothermia, Resuscitation
Brief summary
The purpose of the study was to demonstrate the safety and feasibility of early intranasal cooling prior to return of spontaneous circulation (ROSC) in the emergency medical services (EMS) environment. It was hypothesized that cooling during the resuscitation attempt would increase ROSC and subsequent survival. The study was not powered to demonstrate statistically-significant differences in any outcome parameter, but was intended as an exploratory study only.
Detailed description
Out of hospital cardiac arrest remains a significant cause of death. Mild hypothermia induced after resuscitation from cardiac arrest has been shown to improve neurologically intact survival. Studies in dogs and rodents have demonstrated improved outcomes when cooling is initiated intra-arrest. The RhinoChill is a non-invasive cooling device through which rapid cooling is achieved via the intranasal delivery of an evaporative coolant into the nasopharynx. Due to its non-invasive and portable nature, the RhinoChill can be used to begin cooling earlier than other cooling devices. Studies performed using the RhinoChill in a porcine model of cardiac arrest suggest that cooling with the RhinoChill prior to the first defibrillation attempt facilitates resuscitation and improves resuscitation rate and neurologically intact survival. This study is being performed to assess the feasibility of using the RhinoChill device in the pre-hospital setting to improve resuscitation from cardiac arrest.
Interventions
DEVICERhinoChill
Nasal catheters are placed and cooling is begun during the resuscitation attempt
OTHERControl
Advanced cardiac life support according to American Heart Association & European Resuscitation Council 2005 Guidelines
Sponsors
BeneChill, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥18 years * Collapse was witnessed * No pulse * Unresponsive to external stimuli
Exclusion criteria
* Have an etiology of cardiac arrest due to trauma, severe bleeding, drug overdose (OD), cerebrovascular accident (CVA), drowning, smoke inhalation, electrocution, hanging * Already hypothermic * Head trauma * Cannot place intra nasal catheters * Do Not Attempt to Resuscitate (DNAR) orders * Known or clinically apparent pregnancy * Have a known coagulopathy (except therapeutically induced) * Are known to have a need for supplemental oxygen * Achieve return of spontaneous circulation (ROSC) prior to initiating cooling * Are reached by emergency medical services (EMS) personnel more than 20 minutes after collapse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Achieve Return of Spontaneous Circulation (ROSC) | 1-hour after arrest | ROSC was defined as the return of an organized rhythm on electrocardiography (ECG) with a palpable pulse that was maintained for at least 20 minutes. |
| Survived to Hospital Discharge | 30 days after arrest | The study end-point was hospital discharge. This outcome measure is the patient count for those that were discharged alive from the hospital. |
| Survived Neurologically-Intact | 30-days after arrest | The Cerebral Performance Categories (CPC) are used to describe neurological outcome. A CPC of 1 or 2 is considered neurologically intact. 1. \- Good cerebral performance: little to no deficit. 2. \- Moderate cerebral disability: capable of independent activities of daily life 3. \- Severe cerebral disability: conscious, but dependent on others for daily support 4. \- Coma or vegetative state 5. \- Death or brain death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events (SAEs) | 7 days after arrest | These were defined serious adverse events that are not direct sequelae of the cardiac arrest itself or the underlying cardiac disease. Therefore, these do not include recurrent arrests occcuring within 24 hours of resuscitation nor deaths due to lack of cardiac and/or neurological recovery. |
| Primary Outcomes in Sub-group With VF/VT as First Rhythm | hospital discharge | ROSC, survival, and neurologically-intact survival |
| 24-hour Adverse Events (AE) | 24 hours after arrest | These were all non-serious adverse events that occurred between the time of enrollment and 24 hours after resuscitation. These did not include a failure to achieve ROSC. |
| Time to Therapeutic Temperature | within 8 hours after enrollment | The therapeutic temperature range for treatment in cardiac arrest is considered to be 32-34C. Time to therapeutic temperature was taken as the first time in which 34C was measured. Tympanic and core temperatures were taken in all patients. |
| Length of Stay | Hospital Discharge | Length of stay data for patients admitted to the hospital will be calculated for: 1. Days on ventilator 2. Days in intensive care without ventilator 3. Days in general ward |
Countries
Belgium, Czechia, Germany, Italy, Sweden
Participant flow
Recruitment details
Patients were recruited by emergency medical system advanced life support personnel over an 8-month period (November 2008 through June 2009). Patients appearing to meet the study criteria were randomized during ongoing resuscitation procedures. Patients that survived to hospital admission were followed until death or hospital discharge.
Pre-assignment details
Due to the emergency nature of the research, patients were often randomized into the study before all exclusion criteria could be ruled out (e.g., Do Not Attempt to Resuscitate (DNAR) orders, drug over-dose (OD), cerebrovascular accident (CVA)). Therefore, patients meeting pre-defined exclusion criteria were not included in the outcome measures.
Participants by arm
| Arm | Count |
|---|---|
| RhinoChill Intra-arrest cooling with the RhinoChill during advanced cardiac life support | 96 |
| Control Advanced cardiac life support (ACLS), only. ACLS procedures were performed in accordance with the European Resuscitation Council 2006 Guidelines. | 104 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 18 | 30 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Pre-defined exclusion | 13 | 3 |
| Overall Study | Was not resuscitated | 50 | 56 |
Baseline characteristics
| Characteristic | Total | Control | RhinoChill |
|---|---|---|---|
| Age Categorical <=18 years | 0 participants | 0 participants | 0 participants |
| Age Categorical >=65 years | 102 participants | 55 participants | 47 participants |
| Age Categorical Between 18 and 65 years | 79 participants | 44 participants | 35 participants |
| Age Continuous | 65 years STANDARD_DEVIATION 14 | 64.8 years STANDARD_DEVIATION 13.5 | 66.4 years STANDARD_DEVIATION 13.2 |
| Bystander CPR Did not receive bystander CPR | 105 participants | 54 participants | 51 participants |
| Bystander CPR Received bystander CPR | 76 participants | 45 participants | 31 participants |
| Elapsed time from collapse until: Advanced Life Support (ALS) Arrived | 12 minutes | 11 minutes | 12 minutes |
| Elapsed time from collapse until: Airway Protected | 17 minutes | 16 minutes | 18 minutes |
| Elapsed time from collapse until: Arrived at Hospital | 60 minutes | 60 minutes | 59 minutes |
| Elapsed time from collapse until: Cooling Initiated | 30 minutes | 113 minutes | 23 minutes |
| Elapsed time from collapse until: EMS CPR Initiated | 8 minutes | 8 minutes | 8 minutes |
| Elapsed time from collapse until: First Defibrillation Shock (VF only) | 12 minutes | 12 minutes | 12 minutes |
| Elapsed time from collapse until: Intravenous (IV) Access Acquired | 16 minutes | 15 minutes | 16 minutes |
| Elapsed time from collapse until: Randomized | 19 minutes | 18 minutes | 20 minutes |
| Elapsed time from collapse until: ROSC Achieved | 31 minutes | 30 minutes | 32 minutes |
| Evaluable Participants Did not meet all Inclusion/Exclusion Criteria | 16 participants | 3 participants | 13 participants |
| Evaluable Participants No data obtained | 3 participants | 2 participants | 1 participants |
| Evaluable Participants Total evaluable | 181 participants | 99 participants | 82 participants |
| First Rhythm Asystole | 84 participants | 44 participants | 40 participants |
| First Rhythm PEA/EMD | 41 participants | 23 participants | 18 participants |
| First Rhythm VF/VT | 56 participants | 32 participants | 24 participants |
| Gender Female | 45 participants | 22 participants | 23 participants |
| Gender Male | 136 participants | 77 participants | 59 participants |
| Region of Enrollment Belgium | 97 participants | 51 participants | 46 participants |
| Region of Enrollment Czech Republic | 6 participants | 4 participants | 2 participants |
| Region of Enrollment Germany | 65 participants | 33 participants | 32 participants |
| Region of Enrollment Italy | 9 participants | 6 participants | 3 participants |
| Region of Enrollment Sweden | 23 participants | 10 participants | 13 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 96 | 3 / 104 |
| serious Total, serious adverse events | 6 / — | 12 / — |
Outcome results
Primary
Achieve Return of Spontaneous Circulation (ROSC)
ROSC was defined as the return of an organized rhythm on electrocardiography (ECG) with a palpable pulse that was maintained for at least 20 minutes.
Time frame: 1-hour after arrest
Population: Only patients meeting all inclusion/exclusion criteria (IC/EC) were included in the analyses. 15 patients were found to not meet all IC/EC after enrollment. 2 more patients were lost to follow-up and 1 patient was crossed over (Control to RhinoChill) and then withdrawn. Informed consent nor data was obtained for any of these patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RhinoChill | Achieve Return of Spontaneous Circulation (ROSC) | 33 participants |
| Control | Achieve Return of Spontaneous Circulation (ROSC) | 43 participants |
Primary
Survived Neurologically-Intact
The Cerebral Performance Categories (CPC) are used to describe neurological outcome. A CPC of 1 or 2 is considered neurologically intact. 1. \- Good cerebral performance: little to no deficit. 2. \- Moderate cerebral disability: capable of independent activities of daily life 3. \- Severe cerebral disability: conscious, but dependent on others for daily support 4. \- Coma or vegetative state 5. \- Death or brain death
Time frame: 30-days after arrest
Population: The set of patients excluding those not meeting IC/EC, not lost to follow-up, or not crossed-over/withdrawn.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RhinoChill | Survived Neurologically-Intact | 11 participants |
| Control | Survived Neurologically-Intact | 9 participants |
Primary
Survived to Hospital Discharge
The study end-point was hospital discharge. This outcome measure is the patient count for those that were discharged alive from the hospital.
Time frame: 30 days after arrest
Population: The set of patients excluding those not meeting IC/EC, not lost to follow-up, or not crossed-over/withdrawn. One RhinoChill patient that achieved ROSC was found to be DNAR upon hospital arrival and was excluded from analyses thereafter. The final number of analyzed RhinoChill patients was therefore 82.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RhinoChill | Survived to Hospital Discharge | 14 participants |
| Control | Survived to Hospital Discharge | 13 participants |
Secondary
24-hour Adverse Events (AE)
These were all non-serious adverse events that occurred between the time of enrollment and 24 hours after resuscitation. These did not include a failure to achieve ROSC.
Time frame: 24 hours after arrest
Population: all enrolled participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RhinoChill | 24-hour Adverse Events (AE) | Other | 0 all participants |
| RhinoChill | 24-hour Adverse Events (AE) | RhinoChill-related | 17 all participants |
| Control | 24-hour Adverse Events (AE) | Other | 3 all participants |
| Control | 24-hour Adverse Events (AE) | RhinoChill-related | 0 all participants |
Secondary
Length of Stay
Length of stay data for patients admitted to the hospital will be calculated for: 1. Days on ventilator 2. Days in intensive care without ventilator 3. Days in general ward
Time frame: Hospital Discharge
Population: Evaluable patients admitted to the hospital
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| RhinoChill | Length of Stay | Survivors - ventilator days | 4.2 days |
| RhinoChill | Length of Stay | Survivors - general ward days | 12.8 days |
| RhinoChill | Length of Stay | Survivors - ICU days (no ventilator) | 2.0 days |
| RhinoChill | Length of Stay | Non-survivors | 3.0 days |
| Control | Length of Stay | Survivors - ICU days (no ventilator) | 3.0 days |
| Control | Length of Stay | Survivors - ventilator days | 8.8 days |
| Control | Length of Stay | Non-survivors | 2.6 days |
| Control | Length of Stay | Survivors - general ward days | 11.5 days |
Secondary
Primary Outcomes in Sub-group With VF/VT as First Rhythm
ROSC, survival, and neurologically-intact survival
Time frame: hospital discharge
Population: Subset of all included patients with VF/VT as the first cardiac rhythm present upon ECG assessment by EMS personnel
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RhinoChill | Primary Outcomes in Sub-group With VF/VT as First Rhythm | Achieved ROSC | 17 participants |
| RhinoChill | Primary Outcomes in Sub-group With VF/VT as First Rhythm | Survived to Hospital Discharge | 10 participants |
| RhinoChill | Primary Outcomes in Sub-group With VF/VT as First Rhythm | Survived Neurologically-Intact | 8 participants |
| Control | Primary Outcomes in Sub-group With VF/VT as First Rhythm | Achieved ROSC | 21 participants |
| Control | Primary Outcomes in Sub-group With VF/VT as First Rhythm | Survived to Hospital Discharge | 10 participants |
| Control | Primary Outcomes in Sub-group With VF/VT as First Rhythm | Survived Neurologically-Intact | 6 participants |
Secondary
Serious Adverse Events (SAEs)
These were defined serious adverse events that are not direct sequelae of the cardiac arrest itself or the underlying cardiac disease. Therefore, these do not include recurrent arrests occcuring within 24 hours of resuscitation nor deaths due to lack of cardiac and/or neurological recovery.
Time frame: 7 days after arrest
Population: All enrolled patients; see additional modified at risk population based on study attrition in the Adverse Event section.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RhinoChill | Serious Adverse Events (SAEs) | 6 all participants |
| Control | Serious Adverse Events (SAEs) | 12 all participants |
Secondary
Time to Therapeutic Temperature
The therapeutic temperature range for treatment in cardiac arrest is considered to be 32-34C. Time to therapeutic temperature was taken as the first time in which 34C was measured. Tympanic and core temperatures were taken in all patients.
Time frame: within 8 hours after enrollment
Population: The subset of patients that were resuscitated and subsequently received in-hospital cooling and reached the designated therapuetic temperatures.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| RhinoChill | Time to Therapeutic Temperature | Time to 34C Core Temperature | 155 minutes |
| RhinoChill | Time to Therapeutic Temperature | Time to 33C Core Temperature | 315 minutes |
| RhinoChill | Time to Therapeutic Temperature | Time to 33C Tympanic Temperature | 170 minutes |
| RhinoChill | Time to Therapeutic Temperature | Time to 34C Tympanic Temperature | 102 minutes |
| Control | Time to Therapeutic Temperature | Time to 33C Tympanic Temperature | 377 minutes |
| Control | Time to Therapeutic Temperature | Time to 34C Core Temperature | 284 minutes |
| Control | Time to Therapeutic Temperature | Time to 34C Tympanic Temperature | 291 minutes |
| Control | Time to Therapeutic Temperature | Time to 33C Core Temperature | 389 minutes |
Post Hoc
Outcomes for Patients Admitted to the Hospital
Suvival and neurologically intact survival
Time frame: Hospital discharge
Population: Subset of patients that achieved ROSC and were subsequently admitted to the hospital.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RhinoChill | Outcomes for Patients Admitted to the Hospital | Survived to Hospital Discharge | 14 participants |
| RhinoChill | Outcomes for Patients Admitted to the Hospital | Survived Neurologically-Intact | 11 participants |
| Control | Outcomes for Patients Admitted to the Hospital | Survived to Hospital Discharge | 13 participants |
| Control | Outcomes for Patients Admitted to the Hospital | Survived Neurologically-Intact | 9 participants |
Post Hoc
Outcomes for Patients Receiving EMS CPR Within 10 Minutes of Collapse That Were Admitted to the Hospital
Time frame: Hospital Discharge
Population: Subset of patients that received EMS CPR within 10 minutes of collapse, achieved ROSC, and were subsequently admitted to the hospital.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RhinoChill | Outcomes for Patients Receiving EMS CPR Within 10 Minutes of Collapse That Were Admitted to the Hospital | Survived to Hospital Discharge | 13 participants |
| RhinoChill | Outcomes for Patients Receiving EMS CPR Within 10 Minutes of Collapse That Were Admitted to the Hospital | Survived Neurologically-Intact | 10 participants |
| Control | Outcomes for Patients Receiving EMS CPR Within 10 Minutes of Collapse That Were Admitted to the Hospital | Survived to Hospital Discharge | 10 participants |
| Control | Outcomes for Patients Receiving EMS CPR Within 10 Minutes of Collapse That Were Admitted to the Hospital | Survived Neurologically-Intact | 6 participants |
Post Hoc
Outcomes for VF Patients Admitted to the Hospital
Survival and neurologically-intact survival for patients found in VF/VT admitted to the hospital
Time frame: Hospital discharge
Population: Subset of patients with an initial rhythm of VF/VT, achieved ROSC and were subsequently admitted to the hospital
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RhinoChill | Outcomes for VF Patients Admitted to the Hospital | All Survivors | 10 participants |
| RhinoChill | Outcomes for VF Patients Admitted to the Hospital | Neurologically-Intact Survivors | 8 participants |
| Control | Outcomes for VF Patients Admitted to the Hospital | All Survivors | 10 participants |
| Control | Outcomes for VF Patients Admitted to the Hospital | Neurologically-Intact Survivors | 6 participants |
Post Hoc
Primary Outcomes in Sub-group Receiving EMS CPR Within 10 Minutes of Collapse
ROSC, Survival, and neurologically-intact survival
Time frame: Hospital discharge
Population: Subset of patients receiving EMS CPR within 10 minutes of collapse (representing 75% of all patients)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RhinoChill | Primary Outcomes in Sub-group Receiving EMS CPR Within 10 Minutes of Collapse | Achieved ROSC | 26 participants |
| RhinoChill | Primary Outcomes in Sub-group Receiving EMS CPR Within 10 Minutes of Collapse | Survived to Hospital Discharge | 13 participants |
| RhinoChill | Primary Outcomes in Sub-group Receiving EMS CPR Within 10 Minutes of Collapse | Survived Neurologically-Intact | 10 participants |
| Control | Primary Outcomes in Sub-group Receiving EMS CPR Within 10 Minutes of Collapse | Achieved ROSC | 35 participants |
| Control | Primary Outcomes in Sub-group Receiving EMS CPR Within 10 Minutes of Collapse | Survived to Hospital Discharge | 10 participants |
| Control | Primary Outcomes in Sub-group Receiving EMS CPR Within 10 Minutes of Collapse | Survived Neurologically-Intact | 6 participants |