Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R01HL129722 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
Not provided
Not provided
Not provided
Not provided
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.
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:
Exclusion Criteria
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | 2 ml of normal saline (n=500) |
|
| sodium nitrite | Experimental | 45 mg IV of sodium nitrite (n=500) or 60 mg IV sodium nitrite (n=500) given during active resuscitation from out of hospital cardiac arrest. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | 500 patients will 2 ml of normal saline |
| |
| sodium nitrite 45 mg |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Survived to Hospital Admission | Patient has sustained pulse at arrival to the emergency department | within 24 hours after out of hospital cardiac arrest |
| Measure | Description | Time Frame |
|---|---|---|
| Survival to Discharge | Patient alive at time of discharge from hospital | within 3-6 months after cardiac arrest |
| Number of Days in ICU | Number of days the patient is admitted to the Intensive Care Unit |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Francis Kim, MD | University of Washington | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Harborview Medical Center | Seattle | Washington | 98104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33433575 | Derived | Kim F, Maynard C, Dezfulian C, Sayre M, Kudenchuk P, Rea T, Sampson D, Olsufka M, May S, Nichol G. Effect of Out-of-Hospital Sodium Nitrite on Survival to Hospital Admission After Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2021 Jan 12;325(2):138-145. doi: 10.1001/jama.2020.24326. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
A total of 1502 were enrolled. A total of 1497 were randomized. 5 patients were excluded due to missing kit information.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | 2 ml of normal saline (n=500) Placebo: 500 patients will 2 ml of normal saline |
| FG001 | Sodium Nitrite 45 mg | 45 mg IV of sodium nitrite (n=500) |
| FG002 | Sodium Nitrite 60 mg | sodium nitrite 60 mg (n=500) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
5 patients were excluded since they were incarcerated or were less than 18 years of age. We were not allowed to use their data. There were 1492 patients available for analysis.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | 2 ml of normal saline Placebo: 500 patients will 2 ml of normal saline |
| BG001 | Sodium Nitrite 45 mg | 45 mg IV of sodium nitrite |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Survived to Hospital Admission | Patient has sustained pulse at arrival to the emergency department | Posted | Count of Participants | Participants | within 24 hours after out of hospital cardiac arrest |
|
Adverse events were collected from time period of randomization to hospital discharge
Other variables (rate of rearrest, use of norepinephrine in the filed) were chosen as respecified safety outcomes
There were no unexpected adverse events observed in this study. Of note, this is not atypical for studies of out of hospital cardiac arrest, because it is very difficult to identify and observe adverse events for patients whose heart has stopped beating.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | 2 ml of normal saline (n=500) Placebo: 500 patients will 2 ml of normal saline |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Re-arrest first 24 hours of hospitalization | Cardiac disorders | Non-systematic Assessment | Loss of pulse during hospitalization. Includes all patients, including patients who died before emergency room or hospitalization. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Positive troponin | Cardiac disorders | Non-systematic Assessment | Troponin level greater than 0.02-0.08 ng/ml at any time during hospitalization Post hoc safety measure The denominator includes patients who died in the emergency department or died before admission to the hospital. |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Francis Kim | University of Washington | 206-897-5264 | fkim@u.washington.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 31, 2020 | Jan 3, 2021 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D058687 | Out-of-Hospital Cardiac Arrest |
| ID | Term |
|---|---|
| D006323 | Heart Arrest |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D012977 | Sodium Nitrite |
| ID | Term |
|---|---|
| D009573 | Nitrites |
| D009608 | Nitrous Acid |
| D017672 | Nitrogen Compounds |
| D007287 | Inorganic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
500 patients will receive 45 mg IV sodium nitrite |
|
| sodium nitrite 60 mg | Drug | 500 patients will receive a dose of 60 mg IV sodium nitrite |
|
| Within first 3 months of hospital admission |
| Survival to 24 Hours | Patient is alive after the first 24 hours after admission to the hospital | within first 24 h after hospital admission |
| Re-arrest | Patient loses pulses during transport to the hospital. Event occurs before admission to hospital. | before hospital arrival |
| Survival to 48 Hours After Admission to Hospital | Patient is alive after first 48 hours after admission to the hospital | within first 48 hours after admission to hospital |
| Survival to 72 Hours After Admission to Hospital | Patient is alive after first 72 hours after admission to the hospital | within first 72 hours after admission to hospital |
| BG002 | Sodium Nitrite 60 mg | 60 mg IV sodium nitrite |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Inter-Quartile Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
|
| Secondary | Survival to Discharge | Patient alive at time of discharge from hospital | Posted | Count of Participants | Participants | within 3-6 months after cardiac arrest |
|
|
|
|
| Secondary | Number of Days in ICU | Number of days the patient is admitted to the Intensive Care Unit | Posted | Mean | Standard Deviation | days | Within first 3 months of hospital admission |
|
|
|
|
| Secondary | Survival to 24 Hours | Patient is alive after the first 24 hours after admission to the hospital | Posted | Count of Participants | Participants | within first 24 h after hospital admission |
|
|
|
|
| Secondary | Re-arrest | Patient loses pulses during transport to the hospital. Event occurs before admission to hospital. | Posted | Count of Participants | Participants | before hospital arrival |
|
|
|
|
| Secondary | Survival to 48 Hours After Admission to Hospital | Patient is alive after first 48 hours after admission to the hospital | Posted | Count of Participants | Participants | within first 48 hours after admission to hospital |
|
|
|
|
| Secondary | Survival to 72 Hours After Admission to Hospital | Patient is alive after first 72 hours after admission to the hospital | Posted | Count of Participants | Participants | within first 72 hours after admission to hospital |
|
|
|
|
| 422 |
| 496 |
| 280 |
| 496 |
| 21 |
| 496 |
| EG001 | Sodium Nitrite 45 mg | 45 mg IV of sodium nitrite (n=500) | 433 | 499 | 249 | 499 | 19 | 499 |
| EG002 | Sodium Nitrite 60 mg | sodium nitrite 60 mg (n=500) | 425 | 497 | 268 | 497 | 15 | 497 |
|
| Pressors in first 24 hours after hospitalization | Cardiac disorders | Non-systematic Assessment | Use of any pressors to support blood pressure during first 24 hours. The denominator includes patients who died in the emergency department or before admission to the hospital |
|
| sustained hypotension in hospital, first 24 hours | Cardiac disorders | Non-systematic Assessment | Systolic blood pressure of less than 90 mmHg during first 24 hours after randomization. |
|
|
Not provided
Not provided
| D017670 |
| Sodium Compounds |
| Mean Difference (Final Values) |
| -0.4 |
| 2-Sided |
| 95 |
| -4.9 |
| 4.0 |
| Superiority |
| Mean Difference (Final Values) |
| 0.5 |
| 2-Sided |
| 95 |
| -2.5 |
| 3.6 |
| Superiority |
| Mean Difference (Final Values) |
| -2.1 |
| 2-Sided |
| 95 |
| -8.0 |
| 3.9 |
| Superiority |
| Mean Difference (Final Values) |
| 5.3 |
| 2-Sided |
| 95 |
| -2.8 |
| 13.3 |
| Superiority |
| Mean Difference (Final Values) |
| -2.1 |
| 2-Sided |
| 95 |
| -7.8 |
| 3.7 |
| Superiority |
| Mean Difference (Final Values) |
| -0.4 |
| 2-Sided |
| 95 |
| -4.9 |
| 4.0 |
| Superiority |