Heart Arrest, Out-Of-Hospital Clinical Trial
— iNOOHCAOfficial title:
Inhaled Nitric Oxide After Out-of-Hospital Cardiac Arrest
Verified date | March 2022 |
Source | University of Pittsburgh |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Phase II double blind (participants and investigator) placebo controlled randomized (1:1) clinical trial of inhaled nitric oxide (iNO) 20 ppm administered over 12h beginning as soon as possible but within 4 h of return of spontaneous circulation (ROSC) from out-of-hospital cardiac arrest (OHCA). Planned enrollment is 180 subjects over 48 months at University of Pittsburgh Medical Center (UPMC) Hospitals with randomization stratified in blocks of 8. Recruitment will be performed under exception from informed consent (EFIC) to facilitate early enrollment and treatment. The study will have a pre-specified safety analysis at the mid-point (after 1 year or 60 patients whichever occurs first). Subjects will be screened by members of the University of Pittsburgh post-cardiac arrest service (PCAS), all of whom will serve as the study co-investigators, and the Research Coordinators. Notification of inclusion under EFIC will be performed as soon as possible by a member of the study team generally to a surrogate as the subjects will be comatose after OHCA.
Status | Terminated |
Enrollment | 57 |
Est. completion date | June 2, 2020 |
Est. primary completion date | May 22, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Intubated and comatose adult (>18 yo) resuscitated from out-of-hospital cardiac arrest (OHCA)* *Cardiac arrest within an emergency department or outpatient medical center will be included). OHCA includes Emergency Medical Service (EMS) witnessed cardiac arrest. - Return of spontaneous circulation (ROSC) within 40 min of CPR initiation - Full Outline of Unresponsiveness (FOUR) Brainstem score = 2 (i.e. patient must have pupil OR corneal reflex at the time of ED presentation or within 1h if sedation/neuromuscular blockade clouds the picture) Exclusion Criteria: - Traumatic etiology of OHCA - Prisoner - Known pregnancy (beta-human chorionic gonadotropin screening is NOT REQUIRED for enrollment in women of appropriate age) - Hemodynamic instability defined as >1 recurrent arrest prior to enrollment OR inability to maintain mean arterial blood pressure (MAP) > 65 using vasopressors and inotropes (ie actively up titrating medications or giving fluid bolus) - Head CT grey-white ratio < 1.2; Head CT is NOT REQUIRED prior to enrollment - Fixed and dilated pupils without another explanation - Known intracranial hemorrhage or acute cerebral infarction; Head CT is NOT REQUIRED prior to enrollment - Malignant EEG upon presentation defined as: myoclonic status epilepticus, non-convulsive status epilepticus, generalized periodic epileptiform discharges. EEG screening is NOT REQUIRED prior to enrollment - ROSC >3h from time of ED arrival (treatment allocation must be within 4h so anything that will prevent this is reason for exclusion) - Alert and interactive patient with minimal evidence of neurologic injury - Plan to extubate within 12 hours - Post-cardiac arrest service (PCAS) physician opinion that patient will die with >95% likelihood. This may be based on: - Multiple medical comorbidities - Late discovery of don not resuscitate (DNR) or advanced directive - Terminal diagnosis (other than OHCA; may have caused OHCA) - Clinical judgement based on current exam and data - Patient is known to be taking phosphodiesterase type 5 (PDE5) inhibitors, soluble guanylyl cyclase (sGC) stimulator, or has a known diagnosis of Chronic thromboembolic pulmonary hypertension (CTEPH), pulmonary hypertension (PAH), or erectile dysfunction - Known enrollment in another acute interventional study. |
Country | Name | City | State |
---|---|---|---|
United States | UPMC McKeesport | McKeesport | Pennsylvania |
United States | UPMC East | Monroeville | Pennsylvania |
United States | UPMC Mercy Hospital | Pittsburgh | Pennsylvania |
United States | UPMC Presbyterian Hospital | Pittsburgh | Pennsylvania |
United States | UPMC Shadyside | Pittsburgh | Pennsylvania |
Lead Sponsor | Collaborator |
---|---|
Cameron Dezfulian | Mallinckrodt |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Participants With Death or Significant Neurological or Cardiac Impairment | Composite of in-hospital death; OR unfavorable discharge location defined as a skilled nursing facility (SNF), long term acute care (LTAC) or hospice; OR New York Heart Association (NYHA) class III/IV heart failure at the time of discharge.*
*In the setting of pre-existing heart failure there must be at least a 1 class decrement (eg III -> IV). If patient was previously housed in a "unfavorable" destination there must be a 1 point decrement (eg from SNF to LTAC or LTAC to hospice). Subjects with pre-existing NYHA IV symptoms or living in hospice are excluded from meeting the respective outcome. |
Hospital discharge (+/- 3 days) | |
Secondary | Number of Subjects Dead | Patient declared dead at designated time point | Hospital discharge (+/- 3 days) | |
Secondary | Number of Subjects Dead | Patient declared dead at designated time point | 30 days after cardiac arrest (+/- 3 days) | |
Secondary | Number of Subjects Dead | Patient declared dead at designated time point | 90 days after cardiac arrest (+/- 3 days) | |
Secondary | Number of Subjects With a Favorable Cerebral Performance Category (CPC) | The cerebral performance category (CPC) is a standardized scale from 1-5 describing neurological and functional outcome with a long history of use in cardiac arrest trials (N Engl J Med 1986; 314:397-403). Lower scores indicate better neurological performance as follows: (1) conscious and alert with normal function or only slight disability, (2) conscious and alert with moderate disability, (3) conscious with severe disability, (4) comatose or in a persistent vegetative state, or (5) dead. CPC will be dichotomized as favorable (1, 2) or unfavorable (3-5) at designated time. | Hospital discharge (+/- 3 days) | |
Secondary | Number of Subjects With a Favorable Cerebral Performance Category (CPC) | The cerebral performance category (CPC) is a standardized scale from 1-5 describing neurological and functional outcome with a long history of use in cardiac arrest trials (N Engl J Med 1986; 314:397-403). Lower scores indicate better neurological performance as follows: (1) conscious and alert with normal function or only slight disability, (2) conscious and alert with moderate disability, (3) conscious with severe disability, (4) comatose or in a persistent vegetative state, or (5) dead. CPC will be dichotomized as favorable (1, 2) or unfavorable (3-5) at designated time. | 30 days after cardiac arrest (+/- 3 days) | |
Secondary | Number of Subjects With a Favorable Cerebral Performance Category (CPC) | The cerebral performance category (CPC) is a standardized scale from 1-5 describing neurological and functional outcome with a long history of use in cardiac arrest trials (N Engl J Med 1986; 314:397-403). Lower scores indicate better neurological performance as follows: (1) conscious and alert with normal function or only slight disability, (2) conscious and alert with moderate disability, (3) conscious with severe disability, (4) comatose or in a persistent vegetative state, or (5) dead. CPC will be dichotomized as favorable (1, 2) or unfavorable (3-5) at designated time. | 90 days after cardiac arrest (+/- 3 days) | |
Secondary | Number of Subjects With a Favorable Modified Rankin Score (mRS) | The modified Rankin Score (mRS) is now recommended by consensus as the best measure of neurologic outcome in cardiac arrest studies (Circulation. 2018;137:e783-e801). The mRS runs from 0-6, where higher numbers are consistent with more severe neurologic impairment up to death (6). The scores correspond to: (0) No symptoms; (1) No significant disability. Able to carry out all usual activities, despite some symptoms.;(2) Slight disability; (3) Moderate disability; (4) Moderately severe disability; (5) Severe disability; (6) Dead. This score was dichotomized as favorable (0-3) or unfavorable (4-6) at the appointed time. | Hospital discharge (+/- 3 days) | |
Secondary | Number of Subjects With a Favorable Modified Rankin Score (mRS) | The modified Rankin Score (mRS) is now recommended by consensus as the best measure of neurologic outcome in cardiac arrest studies (Circulation. 2018;137:e783-e801). The mRS runs from 0-6, where higher numbers are consistent with more severe neurologic impairment up to death (6). The scores correspond to: (0) No symptoms; (1) No significant disability. Able to carry out all usual activities, despite some symptoms.;(2) Slight disability; (3) Moderate disability; (4) Moderately severe disability; (5) Severe disability; (6) Dead. This score was dichotomized as favorable (0-3) or unfavorable (4-6) at the appointed time. | 30 days after cardiac arrest (+/- 3 days) | |
Secondary | Number of Subjects With a Favorable Modified Rankin Score (mRS) | The modified Rankin Score (mRS) is now recommended by consensus as the best measure of neurologic outcome in cardiac arrest studies (Circulation. 2018;137:e783-e801). The mRS runs from 0-6, where higher numbers are consistent with more severe neurologic impairment up to death (6). The scores correspond to: (0) No symptoms; (1) No significant disability. Able to carry out all usual activities, despite some symptoms.;(2) Slight disability; (3) Moderate disability; (4) Moderately severe disability; (5) Severe disability; (6) Dead. This score was dichotomized as favorable (0-3) or unfavorable (4-6) at the appointed time. | 90 days after cardiac arrest (+/- 3 days) | |
Secondary | Number of Subjects Discharged to a Favorable Destination | Favorable discharge destination was defined as discharge from the hospital to home or inpatient rehabilitation. Unfavorable discharge destination was defined as discharge to a skilled nursing facility, long term acute care facility, hospice or death. | Hospital discharge (+/- 3 days) | |
Secondary | Barthel Index (Activities of Daily Living) | Barthel Index of Independence in Activities of Daily Living scored as a continuous 0-100 at designated time. A higher score indicates improved ability to independently perform the activities of daily living. | Hospital discharge (+/- 3 days) | |
Secondary | Barthel Index (Activities of Daily Living) | Barthel Index of Independence in Activities of Daily Living scored as a continuous 0-100 at designated time. A higher score indicates improved ability to independently perform the activities of daily living. | 30 days after cardiac arrest (+/- 3 days) | |
Secondary | Barthel Index (Activities of Daily Living) | Barthel Index of Independence in Activities of Daily Living scored as a continuous 0-100 at designated time. A higher score indicates improved ability to independently perform the activities of daily living. | 90 days after cardiac arrest (+/- 3 days) | |
Secondary | Time to Awakening | Time in hours until subject is noted to follow commands. Subjects exceeding 96 hours of coma and those that die without awakening will be designated as 100. | Within 4 days of cardiac arrest | |
Secondary | Methemoglobin Level | Methemoglobin content as proportion (%) of total hemoglobin | Prior to study drug | |
Secondary | Methemoglobin Level | Methemoglobin content as proportion (%) of total hemoglobin | 6 hours after study drug initiated | |
Secondary | Methemoglobin Level | Methemoglobin content as proportion (%) of total hemoglobin | 12 hours after study drug initiated | |
Secondary | Diastolic Blood Pressure | Measured by arterial line | Hourly from 0 - 12 hours of study drug | |
Secondary | Systolic Blood Pressure | Measured by arterial line | Hourly from 0 - 12 hours of study drug | |
Secondary | Heart Rate | Calculated from continuous telemetry by monitor | Hourly from 0 - 12 hours of study drug |
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