Heart Arrest, Out-Of-HospitalPhase 2iNOOHCANCT03079102
Inhaled Nitric Oxide After Out-of-Hospital Cardiac Arrest
A Phase 2 study testing Nitric Oxide and Nitrogen in people with Heart Arrest, Out-Of-Hospital, run by Cameron Dezfulian at 5 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Arrest, Out-Of-Hospital
- What is being tested?
- Nitric Oxide and Nitrogen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 57 participants
- Where
- 5 sitesUnited States
- Study dates
- 26 Aug 2017to 2 Jun 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 18Show fewer
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
UPMC McKeesport
McKeesport, Pennsylvania, 15132
UPMC East
Monroeville, Pennsylvania, 15219
UPMC Presbyterian Hospital
Pittsburgh, Pennsylvania, 15213
UPMC Mercy Hospital
Pittsburgh, Pennsylvania, 15219
UPMC Shadyside
Pittsburgh, Pennsylvania, 15232
About this study
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.
Read the detailed description
Subjects will be identified upon emergency department (ED) arrival or upon transfer from an outside facility and screened for enrollment by a PCAS physician as soon as possible. Eligible patients will have receive any required resuscitation (including central venous and arterial line placement, endotracheal intubation and hemodynamic resuscitation as needed) prior to having baseline labs and studies performed. Subjects will then be started on study drug delivered via the mechanical ventilator with a concealed canister (subject, providers and outcome assessors blind to treatment assignment). Randomization will be performed 1:1 in blocks of 8 using a random number generator. A randomization list will be prepared in advance by the director of respiratory therapy (RT) at each site and verified by a company representative. These individuals (who are not part of the study team) will be unblinded and assure that allocation to placebo and intervention is accurate. The allocation list will assign study drug canisters (by barcode) to each subject in order of study ID. Treatment assignment will be revealed after opening a sealed opaque envelope once enrollment is confirmed by a physician investigator. Study drug will then be administered by RT based on allocation. During study drug administration hourly vital signs will be obtained and methemoglobin levels for safety. Study drug will be weaned off after 12h over the course of 1h (10, 5, 4, 3, 2, 1 ppm each for 10 min) prior to discontinuation. Subjects will then receive standard post-resuscitation care with outcomes assessed by a blinded study team member (see below for outcomes).
Additional clinical variables to be collected Demographics and baseline function. Age, sex, race, maximum education level, employment status, marital status, Barthel activities of daily living (ADL) index prior to OHCA.
Arrest data. Location of OHCA, witnessed, bystander cardiopulmonary resuscitation (CPR), estimated no flow and low flow times, presenting rhythm, doses of epinephrine administered, shocks administered, recurrent arrest, date and time of ROSC.
Medical comorbidities. Diabetes, hypertension, active smoking, hyperlipidemia, chronic obstructive pulmonary disease (COPD), hypertension, drug abuse, prior myocardial infarction, prior coronary artery bypass grafting (CABG), prior coronary angiography with angioplasty or stent, congestive heart failure (EF on last echocardiogram [ECHO] prior to OHCA), obstructive sleep apnea, pulmonary hypertension, calculated Charlson comorbidity index (CCI).
Home medications. Statins, nitrates, anticoagulation, antiplatelet agents Hospital Interventions. Coronary angiography, percutaneous coronary intervention, CABG, mechanical ventilation hours and fraction of inspired oxygen (FiO2) from 0-24h after therapy start In-hospital medications. Alteplase, anti-epileptic medication use (valproate, phenytoin, lacosamide, levetiracetam), neurostimulants (methylphenidate, bromocriptine, modafinil, amantadine), cumulative dose of fentanyl, propofol, midazolam, cis-atracurium and vecuronium in at 24 (+/- 12 hours), 48 (+/- 12 hours), and 72 (+/- 12 hours) hours after therapy initiation
Data Storage Subjects will be assigned a study identifier (ID) upon entry and all data/samples stored using that ID. Linkage to patient identifiers will be maintained in a secure spreadsheet and will include name, date of birth and medical record number. Clinical data will be entered on case report forms (source documentation) which will be stored in a locked filing cabinet within a locked office assigned to the study team. Deidentified clinical and lab data will all be subsequently entered from the case report forms into a web based database (REDCap) to be maintained by Dr. Dezfulian's research assistant who has prior experience from other studies.
Statistical Analysis Plan Continuous data will be compared using t-tests and repeated measures ANOVA to compare between iNO and placebo groups at multiple times. Dichotomous outcomes including the primary endpoint will be compared by chi squared test. Time to awakening and 90d survival will be compared by log rank test of Kaplan-Meier survival plots. All tests will be two tailed with unadjusted p<0.05 considered significant. In the event of a differential distribution of baseline variables strongly associated with outcome (univariate OR >2), dichotomous outcomes will be adjusted for these baseline variables.
- Conditions
- Heart Arrest, Out-Of-Hospital
- Being tested
- Nitric Oxide, Nitrogen
- Medical subject headings
- Out-of-Hospital Cardiac Arrest
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric OxideDrug
Also called inhaled nitric oxide, iNO, iNOMax
An endogenous gaseous signaling molecule which stimulates soluble guanylate cyclase and may act via S-nitrosation, nitrite/nitrate or nitrated fatty acid formation.
NitrogenDrug
Also called Placebo
Nitrogen is the carrier gas (vehicle) for iNO. Subjects receiving placebo will receive equivalent doses of nitrogen.
| Study group | Role | What they receive |
|---|---|---|
| inhaled nitric oxide (iNO) | Experimental | 20 ppm iNO delivered via mechanical ventilator connected to the iNO ventilator delivery system (iNOvent). Drug will be started as soon as possible after return of spontaneous circulation (ROSC) but no later than 4h after ROSC. Study drug will be dosed for 12h then tapered off over 1h. Receives: Drug: Nitric Oxide |
| Placebo | Placebo comparator | Nitrogen carrier gas delivered by identical system with similar dose/taper. Receives: Drug: Nitrogen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Hospital discharge (+/- 3 days)
Secondary outcomes (20)
Number of Subjects Dead
Patient declared dead at designated time point
Measured: Hospital discharge (+/- 3 days)
Number of Subjects Dead
Patient declared dead at designated time point
Measured: 30 days after cardiac arrest (+/- 3 days)
Number of Subjects Dead
Patient declared dead at designated time point
Measured: 90 days after cardiac arrest (+/- 3 days)
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.
Measured: Hospital discharge (+/- 3 days)
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.
Measured: 30 days after cardiac arrest (+/- 3 days)
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.
Measured: 90 days after cardiac arrest (+/- 3 days)
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.
Measured: Hospital discharge (+/- 3 days)
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.
Measured: 30 days after cardiac arrest (+/- 3 days)
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.
Measured: 90 days after cardiac arrest (+/- 3 days)
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.
Measured: Hospital discharge (+/- 3 days)
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.
Measured: Hospital discharge (+/- 3 days)
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.
Measured: 30 days after cardiac arrest (+/- 3 days)
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.
Measured: 90 days after cardiac arrest (+/- 3 days)
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.
Measured: Within 4 days of cardiac arrest
Methemoglobin Level
Methemoglobin content as proportion (%) of total hemoglobin
Measured: Prior to study drug
Methemoglobin Level
Methemoglobin content as proportion (%) of total hemoglobin
Measured: 6 hours after study drug initiated
Methemoglobin Level
Methemoglobin content as proportion (%) of total hemoglobin
Measured: 12 hours after study drug initiated
Diastolic Blood Pressure
Measured by arterial line
Measured: Hourly from 0 - 12 hours of study drug
Systolic Blood Pressure
Measured by arterial line
Measured: Hourly from 0 - 12 hours of study drug
Heart Rate
Calculated from continuous telemetry by monitor
Measured: Hourly from 0 - 12 hours of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2017
- Study start26 Aug 2017
- Primary completion22 May 2020
- Study completion2 Jun 2020
Why it stopped: Slow enrollment and planned change of institution by PI
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Arrest, Out-Of-HospitalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomized 1:1 to either placebo or active study drug (iNO). This will be stratified within blocks of 8 subjects at each center.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cameron Dezfulian
- Sponsor type
- University, hospital or other
- Collaborators
- Mallinckrodt
- Responsible party
- Sponsor-investigator, Cameron Dezfulian, University of Pittsburgh
- Investigators
- Cameron Dezfulian, MD, Principal investigator, Assistant Professor of Critical Care Medicine and Clinical and Translational Science
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03079102
- Sponsor's protocol ID
- PRO16100408
- Acronym
- iNOOHCA
- Status last verified
- Mar 2022
- First submitted
- 5 Jan 2017
- Last updated
- 25 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Magliocca A, Fries M. Inhaled gases as novel neuroprotective therapies in the postcardiac arrest period. Curr Opin Crit Care. 2021 Jun 1;27(3):255-260. doi: 10.1097/MCC.0000000000000820.
PubMed 33769417
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled Nitric Oxide After Out-of-Hospital Cardiac Arrest
- ClinicalTrials.gov ID
- NCT03079102
- Acronym / sponsor ID
- iNOOHCA / PRO16100408
- Conditions
- Heart Arrest, Out-Of-Hospital
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment and planned change of institution by PI
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Cameron DezfulianUniversity, hospital or other
- Collaborators
- Mallinckrodt
- Study start
- 26 Aug 2017 (actual)
- Primary completion
- 22 May 2020 (actual)
- Study completion
- 2 Jun 2020 (actual)
- First posted
- 14 Mar 2017 (actual)
- Results
- Posted 25 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Subjects will be identified upon emergency department (ED) arrival or upon transfer from an outside facility and screened for enrollment by a PCAS physician as soon as possible. Eligible patients will have receive any required resuscitation (including central venous and arterial line placement, endotracheal intubation and hemodynamic resuscitation as needed) prior to having baseline labs and studies performed. Subjects will then be started on study drug delivered via the mechanical ventilator with a concealed canister (subject, providers and outcome assessors blind to treatment assignment). Randomization will be performed 1:1 in blocks of 8 using a random number generator. A randomization list will be prepared in advance by the director of respiratory therapy (RT) at each site and verified by a company representative. These individuals (who are not part of the study team) will be unblinded and assure that allocation to placebo and intervention is accurate. The allocation list will assign study drug canisters (by barcode) to each subject in order of study ID. Treatment assignment will be revealed after opening a sealed opaque envelope once enrollment is confirmed by a physician investigator. Study drug will then be administered by RT based on allocation. During study drug administration hourly vital signs will be obtained and methemoglobin levels for safety. Study drug will be weaned off after 12h over the course of 1h (10, 5, 4, 3, 2, 1 ppm each for 10 min) prior to discontinuation. Subjects will then receive standard post-resuscitation care with outcomes assessed by a blinded study team member (see below for outcomes).
Additional clinical variables to be collected Demographics and baseline function. Age, sex, race, maximum education level, employment status, marital status, Barthel activities of daily living (ADL) index prior to OHCA.
Arrest data. Location of OHCA, witnessed, bystander cardiopulmonary resuscitation (CPR), estimated no flow and low flow times, presenting rhythm, doses of epinephrine administered, shocks administered, recurrent arrest, date and time of ROSC.
Medical comorbidities. Diabetes, hypertension, active smoking, hyperlipidemia, chronic obstructive pulmonary disease (COPD), hypertension, drug abuse, prior myocardial infarction, prior coronary artery bypass grafting (CABG), prior coronary angiography with angioplasty or stent, congestive heart failure (EF on last echocardiogram [ECHO] prior to OHCA), obstructive sleep apnea, pulmonary hypertension, calculated Charlson comorbidity index (CCI).
Home medications. Statins, nitrates, anticoagulation, antiplatelet agents Hospital Interventions. Coronary angiography, percutaneous coronary intervention, CABG, mechanical ventilation hours and fraction of inspired oxygen (FiO2) from 0-24h after therapy start In-hospital medications. Alteplase, anti-epileptic medication use (valproate, phenytoin, lacosamide, levetiracetam), neurostimulants (methylphenidate, bromocriptine, modafinil, amantadine), cumulative dose of fentanyl, propofol, midazolam, cis-atracurium and vecuronium in at 24 (+/- 12 hours), 48 (+/- 12 hours), and 72 (+/- 12 hours) hours after therapy initiation
Data Storage Subjects will be assigned a study identifier (ID) upon entry and all data/samples stored using that ID. Linkage to patient identifiers will be maintained in a secure spreadsheet and will include name, date of birth and medical record number. Clinical data will be entered on case report forms (source documentation) which will be stored in a locked filing cabinet within a locked office assigned to the study team. Deidentified clinical and lab data will all be subsequently entered from the case report forms into a web based database (REDCap) to be maintained by Dr. Dezfulian's research assistant who has prior experience from other studies.
Statistical Analysis Plan Continuous data will be compared using t-tests and repeated measures ANOVA to compare between iNO and placebo groups at multiple times. Dichotomous outcomes including the primary endpoint will be compared by chi squared test. Time to awakening and 90d survival will be compared by log rank test of Kaplan-Meier survival plots. All tests will be two tailed with unadjusted p<0.05 considered significant. In the event of a differential distribution of baseline variables strongly associated with outcome (univariate OR >2), dichotomous outcomes will be adjusted for these baseline variables.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Subjects will be randomized 1:1 to either placebo or active study drug (iNO). This will be stratified within blocks of 8 subjects at each center.
| Arm | Type | Receives |
|---|---|---|
| inhaled nitric oxide (iNO) | Experimental | Drug: Nitric Oxide20 ppm iNO delivered via mechanical ventilator connected to the iNO ventilator delivery system (iNOvent). Drug will be started as soon as possible after return of spontaneous circulation (ROSC) but no later than 4h after ROSC. Study drug will be dosed for 12h then tapered off over 1h. |
| Placebo | Placebo comparator | Drug: NitrogenNitrogen carrier gas delivered by identical system with similar dose/taper. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitric OxideAlso: inhaled nitric oxide, iNO, iNOMaxAn endogenous gaseous signaling molecule which stimulates soluble guanylate cyclase and may act via S-nitrosation, nitrite/nitrate or nitrated fatty acid formation. | Drug | inhaled nitric oxide (iNO) |
| NitrogenAlso: PlaceboNitrogen is the carrier gas (vehicle) for iNO. Subjects receiving placebo will receive equivalent doses of nitrogen. | Drug | Placebo |
Primary outcome
Number of Participants With Death or Significant Neurological or Cardiac Impairment
Time frame: Hospital discharge (+/- 3 days)
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.
20 secondary outcomes
Number of Subjects Dead
Time frame: Hospital discharge (+/- 3 days)
Number of Subjects Dead
Time frame: 30 days after cardiac arrest (+/- 3 days)
Number of Subjects Dead
Time frame: 90 days after cardiac arrest (+/- 3 days)
Number of Subjects With a Favorable Cerebral Performance Category (CPC)
Time frame: Hospital discharge (+/- 3 days)
Number of Subjects With a Favorable Cerebral Performance Category (CPC)
Time frame: 30 days after cardiac arrest (+/- 3 days)
Number of Subjects With a Favorable Cerebral Performance Category (CPC)
Time frame: 90 days after cardiac arrest (+/- 3 days)
Number of Subjects With a Favorable Modified Rankin Score (mRS)
Time frame: Hospital discharge (+/- 3 days)
Number of Subjects With a Favorable Modified Rankin Score (mRS)
Time frame: 30 days after cardiac arrest (+/- 3 days)
Number of Subjects With a Favorable Modified Rankin Score (mRS)
Time frame: 90 days after cardiac arrest (+/- 3 days)
Number of Subjects Discharged to a Favorable Destination
Time frame: Hospital discharge (+/- 3 days)
Barthel Index (Activities of Daily Living)
Time frame: Hospital discharge (+/- 3 days)
Barthel Index (Activities of Daily Living)
Time frame: 30 days after cardiac arrest (+/- 3 days)
Barthel Index (Activities of Daily Living)
Time frame: 90 days after cardiac arrest (+/- 3 days)
Time to Awakening
Time frame: Within 4 days of cardiac arrest
Methemoglobin Level
Time frame: Prior to study drug
Methemoglobin Level
Time frame: 6 hours after study drug initiated
Methemoglobin Level
Time frame: 12 hours after study drug initiated
Diastolic Blood Pressure
Time frame: Hourly from 0 - 12 hours of study drug
Systolic Blood Pressure
Time frame: Hourly from 0 - 12 hours of study drug
Heart Rate
Time frame: Hourly from 0 - 12 hours of study drug
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33769417Magliocca A, Fries M. Inhaled gases as novel neuroprotective therapies in the postcardiac arrest period. Curr Opin Crit Care. 2021 Jun 1;27(3):255-260. doi: 10.1097/MCC.0000000000000820.
- Individual participant dataSharing planned: No
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Cardiopulmonary Resuscitation, Out-of-Hospital Cardiac Arrest
Not yet recruiting
Execution of Prehospital Transesophageal Echocardiography During Cardiopulmonary Resuscitation in Patients With Out-of-hospital Cardiac Arrest
Out-of-hospital Cardiac Arrest (OHCA)
Active, not recruiting
The REVIVE-PEEP Trial: Positive End-expiratory Pressure Versus Sham Valve/Zero End-expiratory Pressure in Cardiopulmonary Resuscitation During Manual Ventilation to Improve Neurological Outcomes at Discharge in Adult Patients Suffering an Out-of-hospital Cardiac Arrest
Cardiac Arrest, Out-Of-Hospital
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cameron Dezfulian, MD principal investigator
Assistant Professor of Critical Care Medicine and Clinical and Translational Science
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitric Oxide and Nitrogen in people with Heart Arrest, Out-Of-Hospital, run by Cameron Dezfulian at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Death or Significant Neurological or Cardiac Impairment (time frame: Hospital discharge (+/- 3 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03079102, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2022.