Cardiac Arrest
Conditions
Keywords
Therapeutic Hypothermia, Out of hospital cardiac arrest, Mild hypothermia, Moderate hypothermia
Brief summary
This trial is currently a single-center, randomized, double-blind investigator initiated prospective clinical trial initiated at the University of Ottawa Heart Institute (UOHI). The plan is to expand the trial shortly as a multi-center project. The patients for this study will be recruited amongst comatose survivors of out-of-hospital cardiac arrest (OHCA). The aim of this study is to determine whether neurologic outcomes at six months are improved with moderate (31 degrees Celsius) versus mild (34 degrees Celsius) therapeutic hypothermia (TH) following return of spontaneous circulation (ROSC) in patients suffering OHCA, with ROSC defined as the resumption of sustained perfusing cardiac activity. The primary outcome will be the proportion of patients experiencing death or a poor neurologic outcome at six months after out of hospital cardiac arrest.
Interventions
Sponsors
Ottawa Heart Institute Research Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Out of hospital cardiac arrest patient 2. Return of spontaneous circulation 3. Glasgow Coma Score equal or lesser than 8.
Exclusion criteria
1. Patients residing in a Nursing Home or patients unable to reside independently, 2. Intracranial bleed responsible for the cardiac arrest, 3. Severe coagulopathy with clinical evidence of major bleeding, 4. Coma that is not attributable to cardiac arrest, 5. Pregnancy, 6. Life expectancy of \< one year due to any cause unrelated to the cardiac arrest, 7. Known coagulation disorder (i.e. INR \>2.0, platelets \<100,000 / mm3), 8. Participation in a study with another investigational device or drug \< four weeks, 9. The Endovascular cooling (ZOLL) device is not available.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Death or Poor Neurologic Outcome at 6 Months | Six months | The primary outcome of the study will be death or poor neurologic outcome at six months. Neurologic outcome will be assessed by a specialist in rehabilitation medicine using the Disability Ratings Scale (DRS. Patients will be judged to have had a poor neurologic outcome if the score on the DRS scale is \>5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Stroke | 30 days and 6 months | Stroke will be classified as hemorrhagic versus non-hemorrhagic. |
| Number of Participants With Bleeding | During index hospitalization, up to 40 days | Bleeding will be assessed using the TIMI definition and will be scored as major or minor. |
| Length of Stay in the Unit | Admission to unit to discharge from unit | — |
| Length of Stay in the Hospital | Admission to hospital to discharge from hospital. | The length of stay participant was in hospital (day of admission to day of discharge from facility) |
| Number of Participants With Cardiogenic Shock | During index hospitalization - day of admission to day of discharge from the facility (*up to 30 days post admission) | The total number of participants who had cardiogenic shock during their admission (day of admission to day of discharge from facility) |
| Number of Mortality | 30 days and 6 months | All cause mortality will be recorded. Mortality will be adjudicated as cardiac versus non-cardiac. |
| Number of Participants With Seizures | During index hospitalization (*up to 45 days post admission day while in hospital) | Count of participants who had seizures while in hospital (day of admission to day of discharge from the facility) |
| Number of Participants With Renal Failure Requiring Renal Replacement Therapy | During index hospitalization - day of admission up to 45 days post admission while in hospital | Participants who required renal replacement therapy (e.g. CRRT, IHD) |
| Number of Participants With Ventilator Associated Pneumonia | During index hospitalization - from day of admission up to 45 days post admission (while in hospital) | The number of participants who developed ventilator associated pneumonia |
| Number of Participants With Stent Thrombosis | Within 6 months of their admission | Participants who are diagnosed with stent thrombosis |
| Number of Participants Discharged Home | Six months | — |
| Number of Participants With Repeat Circulatory Arrest Requiring Cardiopulmonary Resuscitation (CPR) | Six months | — |
Countries
Canada
Participant flow
Recruitment details
Patients with out-of-hospital cardiac arrest surviving to hospital admission and referred for post-cardiac arrest care were recruited.
Participants by arm
| Arm | Count |
|---|---|
| Moderate Hypothermia Therapeutic hypothermia at 31 degrees celsius
Therapeutic Hypothermia | 184 |
| Mild Hypothermia Therapeutic Hypothermia at 34 degrees Celsius
Therapeutic Hypothermia | 183 |
| Total | 367 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 3 |
| Overall Study | Withdrawal by Subject | 8 | 10 |
Baseline characteristics
| Characteristic | Mild Hypothermia | Total | Moderate Hypothermia |
|---|---|---|---|
| Age, Continuous | 61.7 years STANDARD_DEVIATION 13.3 | 61.5 years STANDARD_DEVIATION 13.6 | 61 years STANDARD_DEVIATION 14.2 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Canada | 183 participants | 367 participants | 184 participants |
| Sex: Female, Male Female | 37 Participants | 69 Participants | 32 Participants |
| Sex: Female, Male Male | 146 Participants | 298 Participants | 152 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 80 / 184 | 75 / 183 |
| other Total, other adverse events | 0 / 184 | 0 / 183 |
| serious Total, serious adverse events | 28 / 184 | 34 / 183 |
Outcome results
Primary
Number of Participants With Death or Poor Neurologic Outcome at 6 Months
The primary outcome of the study will be death or poor neurologic outcome at six months. Neurologic outcome will be assessed by a specialist in rehabilitation medicine using the Disability Ratings Scale (DRS. Patients will be judged to have had a poor neurologic outcome if the score on the DRS scale is \>5.
Time frame: Six months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Hypothermia | Number of Participants With Death or Poor Neurologic Outcome at 6 Months | 89 Participants |
| Mild Hypothermia | Number of Participants With Death or Poor Neurologic Outcome at 6 Months | 83 Participants |
Secondary
Length of Stay in the Hospital
The length of stay participant was in hospital (day of admission to day of discharge from facility)
Time frame: Admission to hospital to discharge from hospital.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate Hypothermia | Length of Stay in the Hospital | 22 days |
| Mild Hypothermia | Length of Stay in the Hospital | 20 days |
Secondary
Length of Stay in the Unit
Time frame: Admission to unit to discharge from unit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate Hypothermia | Length of Stay in the Unit | 10 days |
| Mild Hypothermia | Length of Stay in the Unit | 7 days |
Secondary
Number of Mortality
All cause mortality will be recorded. Mortality will be adjudicated as cardiac versus non-cardiac.
Time frame: 30 days and 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Hypothermia | Number of Mortality | 80 Participants |
| Mild Hypothermia | Number of Mortality | 75 Participants |
Secondary
Number of Participants Discharged Home
Time frame: Six months
Population: Survivors discharged to home from hospital.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Hypothermia | Number of Participants Discharged Home | 93 Participants |
| Mild Hypothermia | Number of Participants Discharged Home | 99 Participants |
Secondary
Number of Participants With Bleeding
Bleeding will be assessed using the TIMI definition and will be scored as major or minor.
Time frame: During index hospitalization, up to 40 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Hypothermia | Number of Participants With Bleeding | 43 Participants |
| Mild Hypothermia | Number of Participants With Bleeding | 36 Participants |
Secondary
Number of Participants With Cardiogenic Shock
The total number of participants who had cardiogenic shock during their admission (day of admission to day of discharge from facility)
Time frame: During index hospitalization - day of admission to day of discharge from the facility (*up to 30 days post admission)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Hypothermia | Number of Participants With Cardiogenic Shock | 71 Participants |
| Mild Hypothermia | Number of Participants With Cardiogenic Shock | 61 Participants |
Secondary
Number of Participants With Renal Failure Requiring Renal Replacement Therapy
Participants who required renal replacement therapy (e.g. CRRT, IHD)
Time frame: During index hospitalization - day of admission up to 45 days post admission while in hospital
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Hypothermia | Number of Participants With Renal Failure Requiring Renal Replacement Therapy | 23 Participants |
| Mild Hypothermia | Number of Participants With Renal Failure Requiring Renal Replacement Therapy | 13 Participants |
Secondary
Number of Participants With Repeat Circulatory Arrest Requiring Cardiopulmonary Resuscitation (CPR)
Time frame: Six months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Hypothermia | Number of Participants With Repeat Circulatory Arrest Requiring Cardiopulmonary Resuscitation (CPR) | 20 Participants |
| Mild Hypothermia | Number of Participants With Repeat Circulatory Arrest Requiring Cardiopulmonary Resuscitation (CPR) | 17 Participants |
Secondary
Number of Participants With Seizures
Count of participants who had seizures while in hospital (day of admission to day of discharge from the facility)
Time frame: During index hospitalization (*up to 45 days post admission day while in hospital)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Hypothermia | Number of Participants With Seizures | 23 Participants |
| Mild Hypothermia | Number of Participants With Seizures | 13 Participants |
Secondary
Number of Participants With Stent Thrombosis
Participants who are diagnosed with stent thrombosis
Time frame: Within 6 months of their admission
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Hypothermia | Number of Participants With Stent Thrombosis | 2 Participants |
| Mild Hypothermia | Number of Participants With Stent Thrombosis | 4 Participants |
Secondary
Number of Participants With Stroke
Stroke will be classified as hemorrhagic versus non-hemorrhagic.
Time frame: 30 days and 6 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Moderate Hypothermia | Number of Participants With Stroke | 30 days | 8 Participants |
| Moderate Hypothermia | Number of Participants With Stroke | 6 months | 8 Participants |
| Mild Hypothermia | Number of Participants With Stroke | 30 days | 3 Participants |
| Mild Hypothermia | Number of Participants With Stroke | 6 months | 3 Participants |
Secondary
Number of Participants With Ventilator Associated Pneumonia
The number of participants who developed ventilator associated pneumonia
Time frame: During index hospitalization - from day of admission up to 45 days post admission (while in hospital)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Hypothermia | Number of Participants With Ventilator Associated Pneumonia | 124 Participants |
| Mild Hypothermia | Number of Participants With Ventilator Associated Pneumonia | 116 Participants |