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Trial record 5 of 198 for:    Recruiting, Not yet recruiting, Available Studies | "Heart Arrest"

Inhaled Nitric Oxide After Out-of-Hospital Cardiac Arrest (iNOOHCA)

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ClinicalTrials.gov Identifier: NCT03079102
Recruitment Status : Recruiting
First Posted : March 14, 2017
Last Update Posted : March 29, 2018
Sponsor:
Collaborator:
Mallinckrodt
Information provided by (Responsible Party):
Cameron Dezfulian, University of Pittsburgh

Brief 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). Planned enrollment is 130 subjects over 24 months at University of Pittsburgh Medical Center (UPMC) Presbyterian and UPMC Mercy 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.

Condition or disease Intervention/treatment Phase
Heart Arrest, Out-Of-Hospital Drug: Nitric Oxide Drug: Nitrogen Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Gas canisters will be marked with a bar code which will be recorded by the study coordinator and available to the study team. Only the respiratory therapy directors will be aware of the canister content (placebo vs. active drug). Treatment assignment will be revealed upon opening a sealed opaque envelope after enrollment has been confirmed.
Primary Purpose: Treatment
Official Title: Inhaled Nitric Oxide After Out-of-Hospital Cardiac Arrest
Actual Study Start Date : August 21, 2017
Estimated Primary Completion Date : August 20, 2020
Estimated Study Completion Date : November 17, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: inhaled nitric oxide (iNO)
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.
Drug: Nitric Oxide
An endogenous gaseous signaling molecule which stimulates soluble guanylate cyclase and may act via S-nitrosation, nitrite/nitrate or nitrated fatty acid formation.

Placebo Comparator: Placebo
Nitrogen carrier gas delivered by identical system with similar dose/taper.
Drug: Nitrogen
Nitrogen is the carrier gas (vehicle) for iNO. Subjects receiving placebo will receive equivalent doses of nitrogen.
Other Name: Placebo




Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. Death [ Time Frame: Hospital discharge (+/- 3 days) ]
    Patient declared dead at designated time point

  2. Death [ Time Frame: 30 days after cardiac arrest (+/- 3 days) ]
    Patient declared dead at designated time point

  3. Death [ Time Frame: 90 days after cardiac arrest (+/- 3 days) ]
    Patient declared dead at designated time point

  4. Cerebral performance category (CPC) [ Time Frame: Hospital discharge (+/- 3 days) ]
    CPC is a standardized scale from 1-5 describing neurological and functional outcome. CPC will be dichotomized as favorable (1, 2) or unfavorable (3-5) at designated time

  5. Cerebral performance category - extended (CPC-E) [ Time Frame: Hospital discharge (+/- 3 days) ]
    CPC-E as a continuous measure (1-5) across each of 6 categories within 48h of discharge

  6. Cerebral performance category - extended (CPC-E) [ Time Frame: 30 days after cardiac arrest (+/- 3 days) ]
    CPC-E as a continuous measure (1-5) across each of 4 categories at designated time assuming patient is discharged from hospital (if subject is hospitalized the 6 category scale designated above will be used)

  7. Cerebral performance category - extended (CPC-E) [ Time Frame: 90 days after cardiac arrest (+/- 3 days) ]
    CPC-E as a continuous measure (1-5) across each of 4 categories at designated time assuming patient is discharged from hospital (if subject is hospitalized the 6 category scale designated above will be used)

  8. Cerebral performance category (CPC) [ Time Frame: 30 days after cardiac arrest (+/- 3 days) ]
    CPC dichotomized as favorable (1, 2) or unfavorable (3-5) at designated time

  9. Cerebral performance category (CPC) [ Time Frame: 90 days after cardiac arrest (+/- 3 days) ]
    CPC dichotomized as favorable (1, 2) or unfavorable (3-5) at designated time

  10. Modified Rankin Score (mRS) [ Time Frame: Hospital discharge (+/- 3 days) ]
    mRS dichotomized as favorable (0-3) or unfavorable (4-6) at hospital discharge

  11. Modified Rankin Score (mRS) [ Time Frame: 30 days after cardiac arrest (+/- 3 days) ]
    mRS dichotomized as favorable (0-3) or unfavorable (4-6) at 30 days post-cardiac arrest

  12. Modified Rankin Score (mRS) [ Time Frame: 90 days after cardiac arrest (+/- 3 days) ]
    mRS dichotomized as favorable (0-3) or unfavorable (4-6) at 90 days post-cardiac arrest

  13. Discharge destination [ Time Frame: Hospital discharge (+/- 3 days) ]
    Location to which patient will be discharged dichotomized as favorable (home or inpatient rehabilitation) or unfavorable (skilled nursing facility, long term acute care, hospice or morgue)

  14. Barthel Index (activities of daily living) [ Time Frame: Hospital discharge (+/- 3 days) ]
    Barthel Index of Independence in Activities of Daily Living scored as a continuous 0-100 at designated time

  15. Barthel Index (activities of daily living) [ Time Frame: 30 days after cardiac arrest (+/- 3 days) ]
    Barthel Index of Independence in Activities of Daily Living scored as a continuous 0-100 at designated time

  16. Barthel Index (activities of daily living) [ Time Frame: 90 days after cardiac arrest (+/- 3 days) ]
    Barthel Index of Independence in Activities of Daily Living scored as a continuous 0-100 at designated time

  17. Time to awakening [ Time Frame: Within 4 days of cardiac arrest ]
    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.

  18. Methemoglobin level [ Time Frame: Prior to study drug ]
    Methemoglobin content as proportion (%) of total hemoglobin

  19. Methemoglobin level [ Time Frame: 6 hours after study drug initiated ]
    Methemoglobin content as proportion (%) of total hemoglobin

  20. Methemoglobin level [ Time Frame: 12 hours after study drug initiated ]
    Methemoglobin content as proportion (%) of total hemoglobin

  21. ECHOcardiogram [ Time Frame: Prior to study drug ]
    Measurement of left ventricular ejection fraction, tricuspid regurgitant velocity and trans-anular pulmonic valve excursion.

  22. ECHOcardiogram [ Time Frame: 12 hours after study drug initiated ]
    Measurement of left ventricular ejection fraction, tricuspid regurgitant velocity and trans-anular pulmonic valve excursion.

  23. Reactive hyperemia [ Time Frame: Prior to study drug ]
    Reactive hyperemia (increase in blood flow from baseline) measured by laser speckle contrast imaging before and after a 1 and 5 min blood pressure cuff occlusion (20 mm Hg above systolic blood pressure)

  24. Reactive hyperemia [ Time Frame: 12 hours after study drug ]
    Reactive hyperemia (increase in blood flow from baseline) measured by laser speckle contrast imaging before and after a 1 and 5 min blood pressure cuff occlusion (20 mm Hg above systolic blood pressure)

  25. Systolic blood pressure [ Time Frame: Hourly from 0 - 12 hours of study drug ]
    Measured by arterial line

  26. Diastolic blood pressure [ Time Frame: Hourly from 0 - 12 hours of study drug ]
    Measured by arterial line

  27. Heart rate [ Time Frame: Hourly from 0 - 12 hours of study drug ]
    Calculated from continuous telemetry by monitor



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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03079102


Contacts
Contact: Sara DiFiore, BA 412-864-2284 difioresm@upmc.edu
Contact: Nicholas Krehel, BS 570-561-3132 NMK54@pitt.edu

Locations
United States, Pennsylvania
UPMC Presbyterian Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Sara DiFiore, BA    412-864-2284    difioresm@upmc.edu   
Principal Investigator: Cameron Dezfulian, MD         
Sub-Investigator: Jon Rittenberger, MD, MSc         
Sub-Investigator: Clifton Callaway, MD, PhD         
Sub-Investigator: Jonathan Elmer, MD, Msc         
Sub-Investigator: Frank X Guyette, MD         
Sub-Investigator: Adam Frisch, MD         
Sub-Investigator: Ankur Doshi, MD         
Sub-Investigator: Bradley Molyneaux, MD         
Sub-Investigator: Alexandra Weissman, MD         
Sub-Investigator: Masashi Okubo, MD         
Sub-Investigator: Nick M Krehel, BS         
Sub-Investigator: Surya Sharma, BS         
UPMC Mercy Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15219
Contact: Sara Difiore, BA    412-864-2284    difioresm@upmc.edu   
Principal Investigator: Cameron Dezfulian, MD         
Sub-Investigator: Ankur Doshi, MD         
Sub-Investigator: Jon Rittenberger, MD         
Sub-Investigator: Clifton Callaway, MD         
Sub-Investigator: Jonathan Elmer, MD         
Sub-Investigator: Francis Guyette, MD         
Sub-Investigator: Kelly Sawyer, MD         
Sub-Investigator: Alexandra Weissman, MD         
Sub-Investigator: Adam Frisch, MD         
Sub-Investigator: Masashi Okubo, MD         
Sub-Investigator: Nick M Krehel, BS         
Sub-Investigator: Surya Sharma, BS         
Sponsors and Collaborators
Cameron Dezfulian
Mallinckrodt
Investigators
Principal Investigator: Cameron Dezfulian, MD Assistant Professor of Critical Care Medicine and Clinical and Translational Science

Responsible Party: Cameron Dezfulian, Assistant Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT03079102     History of Changes
Other Study ID Numbers: PRO16100408
First Posted: March 14, 2017    Key Record Dates
Last Update Posted: March 29, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Heart Arrest
Out-of-Hospital Cardiac Arrest
Heart Diseases
Cardiovascular Diseases
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Gasotransmitters
Protective Agents