Out-Of-Hospital Cardiac Arrest
Conditions
Brief summary
In this clinical study, a total of 1500 patients with out-of-hospital cardiac arrest in Seattle/King County will be enrolled. This will be a randomized clinical trial and patients will receive either two different doses of IV sodium nitrite (45 mg or 60 mg) or placebo during resuscitation in the field by paramedics. The primary outcome will be proportion of patients surviving to hospital admission.
Detailed description
The hemodynamic effects of the optimal dose of IV nitrite administered in patients with cardiac arrest are unknown. A significant negative hemodynamic effect from nitrite would decrease the proportion of patients admitted to the hospital, increase rate of re-arrest, or increase the need for vasopressor support in the field. In Seattle/King County, typically 40% of out-of-hospital cardiac arrest patients attended to by paramedics have Return of spontaneous circulation (ROSC) and are admitted to the hospital. In this study, 1500 patients with out-of-hospital cardiac arrest who are undergoing resuscitation by paramedics will be randomized to receive placebo (n=500) or 45 mg IV (n=500) or 60 mg dose (n=500) of sodium nitrite. The study will have 80% power to detect an absolute increase in hospital admission rate of 8% (1-sided .05 level test for each of the two comparisons (45 mg vs placebo and 60 mg vs placebo, no adjustment for multiple comparisons), with a hospital admission rate of 40% in the placebo group and with one interim analysis and stopping only for potential futility and/or harm). The investigators will examine the proportion of patients who survive to discharge as a secondary measure of efficacy. Patients will be eligible for this study if: 1. Intravenous access (IV)/intraosseous access(IO) 2. Cardiac arrest, either Ventricular Fibrillation (VF) or non-VF patients receiving Advanced Cardiac Life Support (ACLS) by Seattle/King County paramedics. 3. Age 18 years or older 4. Comatose Exclusion Criteria 1. Traumatic cause of cardiac arrest 2. Prisoner, pregnancy, age less than 18 (special population/vulnerable population) 3. Known DNAR 4. Drowning as cause of arrest.
Interventions
DRUGPlacebo
500 patients will 2 ml of normal saline
DRUGsodium nitrite 45 mg
500 patients will receive 45 mg IV sodium nitrite
DRUGsodium nitrite 60 mg
500 patients will receive a dose of 60 mg IV sodium nitrite
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
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
* Cardiac arrest, either VF or non-VF, patients receiving ACLS by paramedics * IV or IO access * Comatose
Exclusion criteria
* traumatic cause of cardiac arrest * prisoner, pregnancy * known DNAR
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Survived to Hospital Admission | within 24 hours after out of hospital cardiac arrest | Patient has sustained pulse at arrival to the emergency department |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days in ICU | Within first 3 months of hospital admission | Number of days the patient is admitted to the Intensive Care Unit |
| Survival to 24 Hours | within first 24 h after hospital admission | Patient is alive after the first 24 hours after admission to the hospital |
| Survival to Discharge | within 3-6 months after cardiac arrest | Patient alive at time of discharge from hospital |
| Survival to 48 Hours After Admission to Hospital | within first 48 hours after admission to hospital | Patient is alive after first 48 hours after admission to the hospital |
| Survival to 72 Hours After Admission to Hospital | within first 72 hours after admission to hospital | Patient is alive after first 72 hours after admission to the hospital |
| Re-arrest | before hospital arrival | Patient loses pulses during transport to the hospital. Event occurs before admission to hospital. |
Countries
United States
Participant flow
Recruitment details
A total of 1502 were enrolled. A total of 1497 were randomized. 5 patients were excluded due to missing kit information.
Participants by arm
| Arm | Count |
|---|---|
| Placebo 2 ml of normal saline
Placebo: 500 patients will 2 ml of normal saline | 496 |
| Sodium Nitrite 45 mg 45 mg IV of sodium nitrite | 499 |
| Sodium Nitrite 60 mg 60 mg IV sodium nitrite | 497 |
| Total | 1,492 |
Baseline characteristics
| Characteristic | Placebo | Sodium Nitrite 45 mg | Sodium Nitrite 60 mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 274 Participants | 256 Participants | 243 Participants | 773 Participants |
| Age, Categorical Between 18 and 65 years | 222 Participants | 242 Participants | 254 Participants | 718 Participants |
| Age, Continuous | 67 years | 65 years | 64 years | 65 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 14 Participants | 10 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 186 Participants | 201 Participants | 192 Participants | 579 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 298 Participants | 284 Participants | 295 Participants | 877 Participants |
| Race/Ethnicity, Customized Asian | 38 Participants | 39 Participants | 31 Participants | 108 Participants |
| Race/Ethnicity, Customized Black | 49 Participants | 58 Participants | 51 Participants | 158 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 5 Participants | 2 Participants | 10 Participants |
| Race/Ethnicity, Customized Unknown | 135 Participants | 109 Participants | 140 Participants | 384 Participants |
| Race/Ethnicity, Customized White | 271 Participants | 288 Participants | 273 Participants | 832 Participants |
| Region of Enrollment United States | 496 participants | 499 participants | 497 participants | 1492 participants |
| Sex: Female, Male Female | 165 Participants | 170 Participants | 167 Participants | 502 Participants |
| Sex: Female, Male Male | 331 Participants | 329 Participants | 330 Participants | 990 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 422 / 496 | 433 / 499 | 425 / 497 |
| other Total, other adverse events | 21 / 496 | 19 / 499 | 15 / 497 |
| serious Total, serious adverse events | 280 / 496 | 249 / 499 | 268 / 497 |
Outcome results
Primary
Number of Participants Who Survived to Hospital Admission
Patient has sustained pulse at arrival to the emergency department
Time frame: within 24 hours after out of hospital cardiac arrest
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Survived to Hospital Admission | 218 Participants |
| Sodium Nitrite 45 mg | Number of Participants Who Survived to Hospital Admission | 205 Participants |
| Sodium Nitrite 60 mg | Number of Participants Who Survived to Hospital Admission | 212 Participants |
p-value: 0.82Chi-squared
p-value: 0.66Chi-squared
Secondary
Number of Days in ICU
Number of days the patient is admitted to the Intensive Care Unit
Time frame: Within first 3 months of hospital admission
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Days in ICU | 6.7 days | Standard Deviation 8.1 |
| Sodium Nitrite 45 mg | Number of Days in ICU | 8.9 days | Standard Deviation 10.4 |
| Sodium Nitrite 60 mg | Number of Days in ICU | 7.3 days | Standard Deviation 7.2 |
p-value: 0.1295% CI: [-0.9, 5.4]Wilcoxon (Mann-Whitney)
p-value: 0.4195% CI: [-2.5, 3.6]Wilcoxon (Mann-Whitney)
Secondary
Re-arrest
Patient loses pulses during transport to the hospital. Event occurs before admission to hospital.
Time frame: before hospital arrival
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Re-arrest | 139 Participants |
| Sodium Nitrite 45 mg | Re-arrest | 130 Participants |
| Sodium Nitrite 60 mg | Re-arrest | 156 Participants |
p-value: 0.9395% CI: [-7.8, 8.6]Chi-squared
p-value: 0.295% CI: [-2.8, 13.3]Chi-squared
Secondary
Survival to 24 Hours
Patient is alive after the first 24 hours after admission to the hospital
Time frame: within first 24 h after hospital admission
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Survival to 24 Hours | 181 Participants |
| Sodium Nitrite 45 mg | Survival to 24 Hours | 170 Participants |
| Sodium Nitrite 60 mg | Survival to 24 Hours | 171 Participants |
p-value: 0.4295% CI: [-8.3, 3.5]Chi-squared
p-value: 0.4995% CI: [-8, 3.9]Chi-squared
Secondary
Survival to 48 Hours After Admission to Hospital
Patient is alive after first 48 hours after admission to the hospital
Time frame: within first 48 hours after admission to hospital
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Survival to 48 Hours After Admission to Hospital | 161 Participants |
| Sodium Nitrite 45 mg | Survival to 48 Hours After Admission to Hospital | 152 Participants |
| Sodium Nitrite 60 mg | Survival to 48 Hours After Admission to Hospital | 151 Participants |
p-value: 0.595% CI: [-7.7, 3.8]Chi-squared
p-value: 0.4895% CI: [-7.8, 3.7]Chi-squared
Secondary
Survival to 72 Hours After Admission to Hospital
Patient is alive after first 72 hours after admission to the hospital
Time frame: within first 72 hours after admission to hospital
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Survival to 72 Hours After Admission to Hospital | 142 Participants |
| Sodium Nitrite 45 mg | Survival to 72 Hours After Admission to Hospital | 133 Participants |
| Sodium Nitrite 60 mg | Survival to 72 Hours After Admission to Hospital | 131 Participants |
p-value: 0.4995% CI: [-6, 2.6]Chi-squared
p-value: 0.8595% CI: [-4.9, 4]Chi-squared
Secondary
Survival to Discharge
Patient alive at time of discharge from hospital
Time frame: within 3-6 months after cardiac arrest
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Survival to Discharge | 74 Participants |
| Sodium Nitrite 45 mg | Survival to Discharge | 66 Participants |
| Sodium Nitrite 60 mg | Survival to Discharge | 72 Participants |
p-value: 0.4495% CI: [-6, 2.6]Chi-squared
p-value: 0.8595% CI: [-4.9, 4]Chi-squared