Traumatic Brain InjuryPhase 3NCT03260569
Inhaled Nitric Oxide in Brain Injury
A Phase 3 study testing Inhaled Nitric Oxide in people with Traumatic Brain Injury, run by University of Cincinnati at 1 site in United States.
Trial summary
This study will evaluate the changes in respiratory mechanics following traumatic brain injury and determine the effect of inhaled nitric oxide on gas exchange. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Inhaled Nitric Oxide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Dec 2018to 28 Dec 2023
- Phase
- Phase 3
- 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
- Hospital admission with traumatic brain injury (penetrating or blunt)
- Requirement for mechanical ventilation
- Glasgow Coma Score > 3
Who cannot join
- Brain death
- Expected survival < 48 hours
- Air leak (bronchopleural fistula, tracheal injury)
- Current inspired oxygen concentration (FiO2) > 0.65
- Hemodynamic instability (systolic blood pressure < 100 mm Hg, cardiac arrhythmia)
- Uncontrolled intracranial pressure (> 20 mm Hg)
Show all 11Show fewer
- Spinal cord injury with hypotension
- Severe acute respiratory distress syndrome (ARDS) (PaO2/FiO2 < 100)
- Chest abbreviated injury score (AIS) > 3
- First rib fracture
- Flail chest
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Respiratory Mechanics Following Brain Injury: The Role of Inhaled Nitric Oxide
This study will evaluate the changes in respiratory mechanics following traumatic brain injury and determine the effect of inhaled nitric oxide on gas exchange.
Read the detailed description
Intubation and mechanical ventilation are common treatments in the care of patients with traumatic brain injury (TBI). Intubation allows for airway control and facilitates removal of respiratory secretions. Mechanical ventilation allows control of arterial carbon dioxide to aid in control of intracranial pressure. Recent evidence suggests that lung protective ventilation (tidal volumes of 6 ml/kg of predicted body weight and moderate positive end expiratory pressure) improves outcomes following brain injury and reduces brain-lung cross talk.
The treatment of respiratory failure in TBI must balance the need to improve lung function with the negative consequences of increased intrathoracic pressure on mean arterial pressure, intracranial pressure and venous return. Traditional treatment of increasing positive end expiratory (PEEP) and mean airway pressure then, represent competing interests. Methods for improving arterial oxygenation while avoiding negative hemodynamic effects are needed.
The impact of head injury on respiratory mechanics has been studied in just a few clinical investigations. (1-3) Of note, the earliest of these noted that the ventilation perfusion (V/Q) matching following TBI was not the result of lung collapse or parenchymal lung disease but secondary to alterations in perfusion. There are three possibilities for this finding:
- redistribution in regional perfusion, which is partially mediated by the hypothalamus
- pulmonary microembolism, leading to increased dead space
- lung surfactant depletion due to excessive sympathetic stimulation and hyperventilation.
The introduction of inhaled pulmonary vasodilators such as inhaled nitric oxide or aerosolized epoprostenol offer an opportunity to improve oxygenation in patients with TBI without increasing airway pressures in the face of V/Q inequalities.
This study will evaluate the changes in respiratory mechanics following TBI and determine the effect of inhaled nitric oxide on gas exchange.
- Conditions
- Traumatic Brain Injury
- Being tested
- Inhaled Nitric Oxide, Placebo
- Keywords
- Mechanical ventilation, Inhaled nitric oxide
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhaled Nitric OxideDrug
Patients randomized to this arm will receive inhaled nitric oxide 20 parts per million.
PlaceboDrug
Nitrogen plus oxygen
| Study group | Role | What they receive |
|---|---|---|
| Inhaled Nitric Oxide | Active comparator | Inhaled nitric oxide at 20 parts per million, administered once during first 36 hours following admission Receives: Drug: Inhaled Nitric Oxide |
| Placebo | Placebo comparator | Nitrogen only, administered once during first 36 hours following admission Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
PaO2
The primary endpoint is the difference in PO2
Measured: at Day 3 of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2017
- Study start12 Dec 2018
- Primary completion28 Dec 2023
- Study completion28 Dec 2023
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 (14)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Following initial non-invasive measurements, patients will be randomized to either an active treatment (inhaled nitric oxide at 30 parts per million) or placebo (nitrogen only). After two hours, measurements will be reassessed. If the patient remains on the mechanical ventilator at 72 hours post-admission, a third set of non-invasive measurements will be taken.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Goodman, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03260569
- Sponsor's protocol ID
- 2017 Goodman
- Status last verified
- Apr 2025
- First submitted
- 22 Aug 2017
- Last updated
- 30 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Schumacker PT, Rhodes GR, Newell JC, Dutton RE, Shah DM, Scovill WA, Powers SR. Ventilation-perfusion imbalance after head trauma. Am Rev Respir Dis. 1979 Jan;119(1):33-43. doi: 10.1164/arrd.1979.119.1.33.
PubMed 420436Cooper KR, Boswell PA. Accurate measurement of functional residual capacity and oxygen consumption of patients on mechanical ventilation. Anaesth Intensive Care. 1983 May;11(2):151-7. doi: 10.1177/0310057X8301100212.
PubMed 6346942Koutsoukou A, Perraki H, Raftopoulou A, Koulouris N, Sotiropoulou C, Kotanidou A, Orfanos S, Roussos C. Respiratory mechanics in brain-damaged patients. Intensive Care Med. 2006 Dec;32(12):1947-54. doi: 10.1007/s00134-006-0406-0. Epub 2006 Oct 20.
PubMed 17053881Gruber A, Reinprecht A, Illievich UM, Fitzgerald R, Dietrich W, Czech T, Richling B. Extracerebral organ dysfunction and neurologic outcome after aneurysmal subarachnoid hemorrhage. Crit Care Med. 1999 Mar;27(3):505-14. doi: 10.1097/00003246-199903000-00026.
PubMed 10199529Holland MC, Mackersie RC, Morabito D, Campbell AR, Kivett VA, Patel R, Erickson VR, Pittet JF. The development of acute lung injury is associated with worse neurologic outcome in patients with severe traumatic brain injury. J Trauma. 2003 Jul;55(1):106-11. doi: 10.1097/01.TA.0000071620.27375.BE.
PubMed 12855888Pelosi P, Severgnini P, Chiaranda M. An integrated approach to prevent and treat respiratory failure in brain-injured patients. Curr Opin Crit Care. 2005 Feb;11(1):37-42. doi: 10.1097/00075198-200502000-00006.
PubMed 15659943Garry PS, Ezra M, Rowland MJ, Westbrook J, Pattinson KT. The role of the nitric oxide pathway in brain injury and its treatment--from bench to bedside. Exp Neurol. 2015 Jan;263:235-43. doi: 10.1016/j.expneurol.2014.10.017. Epub 2014 Oct 29.
PubMed 25447937Terpolilli NA, Kim SW, Thal SC, Kuebler WM, Plesnila N. Inhaled nitric oxide reduces secondary brain damage after traumatic brain injury in mice. J Cereb Blood Flow Metab. 2013 Feb;33(2):311-8. doi: 10.1038/jcbfm.2012.176. Epub 2012 Nov 28.
PubMed 23188422Papadimos TJ, Medhkour A, Yermal S. Successful use of inhaled nitric oxide to decrease intracranial pressure in a patient with severe traumatic brain injury complicated by acute respiratory distress syndrome: a role for an anti-inflammatory mechanism? Scand J Trauma Resusc Emerg Med. 2009 Feb 17;17:5. doi: 10.1186/1757-7241-17-5.
PubMed 19222848Papadimos TJ. The beneficial effects of inhaled nitric oxide in patients with severe traumatic brain injury complicated by acute respiratory distress syndrome: a hypothesis. J Trauma Manag Outcomes. 2008 Jan 14;2(1):1. doi: 10.1186/1752-2897-2-1.
PubMed 18272001Vavilala MS, Roberts JS, Moore AE, Newell DW, Lam AM. The influence of inhaled nitric oxide on cerebral blood flow and metabolism in a child with traumatic brain injury. Anesth Analg. 2001 Aug;93(2):351-3 , 3rd contents page. doi: 10.1097/00000539-200108000-00023.
PubMed 11473859Dellinger RP, Zimmerman JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, Davis K Jr, Hyers TM, Papadakos P. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med. 1998 Jan;26(1):15-23. doi: 10.1097/00003246-199801000-00011.
PubMed 9428538Lundin S, Mang H, Smithies M, Stenqvist O, Frostell C. Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide. Intensive Care Med. 1999 Sep;25(9):911-9. doi: 10.1007/s001340050982.
PubMed 10501745Price AD, Baucom MR, Blakeman TC, Smith M, Gomaa D, Caskey C, Pritts T, Strilka R, Branson RD, Goodman MD. Just Say NO: Inhaled Nitric Oxide Effect on Respiratory Parameters Following Traumatic Brain Injury in Humans and a Porcine Model. J Surg Res. 2024 Apr;296:497-506. doi: 10.1016/j.jss.2023.12.045. Epub 2024 Feb 6.
PubMed 38325012
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Respiratory Mechanics Following Brain Injury: The Role of Inhaled Nitric Oxide
- ClinicalTrials.gov ID
- NCT03260569
- Acronym / sponsor ID
- 2017 Goodman
- Conditions
- Traumatic Brain Injury
- Keywords
- Mechanical ventilation, Inhaled nitric oxide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Study start
- 12 Dec 2018 (actual)
- Primary completion
- 28 Dec 2023 (actual)
- Study completion
- 28 Dec 2023 (actual)
- First posted
- 24 Aug 2017 (actual)
- Results
- Posted 30 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the changes in respiratory mechanics following traumatic brain injury and determine the effect of inhaled nitric oxide on gas exchange.
Detailed description
Intubation and mechanical ventilation are common treatments in the care of patients with traumatic brain injury (TBI). Intubation allows for airway control and facilitates removal of respiratory secretions. Mechanical ventilation allows control of arterial carbon dioxide to aid in control of intracranial pressure. Recent evidence suggests that lung protective ventilation (tidal volumes of 6 ml/kg of predicted body weight and moderate positive end expiratory pressure) improves outcomes following brain injury and reduces brain-lung cross talk.
The treatment of respiratory failure in TBI must balance the need to improve lung function with the negative consequences of increased intrathoracic pressure on mean arterial pressure, intracranial pressure and venous return. Traditional treatment of increasing positive end expiratory (PEEP) and mean airway pressure then, represent competing interests. Methods for improving arterial oxygenation while avoiding negative hemodynamic effects are needed.
The impact of head injury on respiratory mechanics has been studied in just a few clinical investigations. (1-3) Of note, the earliest of these noted that the ventilation perfusion (V/Q) matching following TBI was not the result of lung collapse or parenchymal lung disease but secondary to alterations in perfusion. There are three possibilities for this finding:
- redistribution in regional perfusion, which is partially mediated by the hypothalamus
- pulmonary microembolism, leading to increased dead space
- lung surfactant depletion due to excessive sympathetic stimulation and hyperventilation.
The introduction of inhaled pulmonary vasodilators such as inhaled nitric oxide or aerosolized epoprostenol offer an opportunity to improve oxygenation in patients with TBI without increasing airway pressures in the face of V/Q inequalities.
This study will evaluate the changes in respiratory mechanics following TBI and determine the effect of inhaled nitric oxide on gas exchange.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Following initial non-invasive measurements, patients will be randomized to either an active treatment (inhaled nitric oxide at 30 parts per million) or placebo (nitrogen only). After two hours, measurements will be reassessed. If the patient remains on the mechanical ventilator at 72 hours post-admission, a third set of non-invasive measurements will be taken.
| Arm | Type | Receives |
|---|---|---|
| Inhaled Nitric Oxide | Active comparator | Drug: Inhaled Nitric OxideInhaled nitric oxide at 20 parts per million, administered once during first 36 hours following admission |
| Placebo | Placebo comparator | Drug: PlaceboNitrogen only, administered once during first 36 hours following admission |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Hospital admission with traumatic brain injury (penetrating or blunt)
- Requirement for mechanical ventilation
- Glasgow Coma Score > 3
Key exclusion criteria (11 listed)
- Brain death
- Expected survival < 48 hours
- Air leak (bronchopleural fistula, tracheal injury)
- Current inspired oxygen concentration (FiO2) > 0.65
- Hemodynamic instability (systolic blood pressure < 100 mm Hg, cardiac arrhythmia)
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 |
|---|---|---|
| Inhaled Nitric OxidePatients randomized to this arm will receive inhaled nitric oxide 20 parts per million. | Drug | Inhaled Nitric Oxide |
| PlaceboNitrogen plus oxygen | Drug | Placebo |
Primary outcome
PaO2
Time frame: at Day 3 of the study
The primary endpoint is the difference in PO2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 420436Schumacker PT, Rhodes GR, Newell JC, Dutton RE, Shah DM, Scovill WA, Powers SR. Ventilation-perfusion imbalance after head trauma. Am Rev Respir Dis. 1979 Jan;119(1):33-43. doi: 10.1164/arrd.1979.119.1.33.
- Background: PubMed 6346942Cooper KR, Boswell PA. Accurate measurement of functional residual capacity and oxygen consumption of patients on mechanical ventilation. Anaesth Intensive Care. 1983 May;11(2):151-7. doi: 10.1177/0310057X8301100212.
- Background: PubMed 17053881Koutsoukou A, Perraki H, Raftopoulou A, Koulouris N, Sotiropoulou C, Kotanidou A, Orfanos S, Roussos C. Respiratory mechanics in brain-damaged patients. Intensive Care Med. 2006 Dec;32(12):1947-54. doi: 10.1007/s00134-006-0406-0. Epub 2006 Oct 20.
- Background: PubMed 10199529Gruber A, Reinprecht A, Illievich UM, Fitzgerald R, Dietrich W, Czech T, Richling B. Extracerebral organ dysfunction and neurologic outcome after aneurysmal subarachnoid hemorrhage. Crit Care Med. 1999 Mar;27(3):505-14. doi: 10.1097/00003246-199903000-00026.
- Background: PubMed 12855888Holland MC, Mackersie RC, Morabito D, Campbell AR, Kivett VA, Patel R, Erickson VR, Pittet JF. The development of acute lung injury is associated with worse neurologic outcome in patients with severe traumatic brain injury. J Trauma. 2003 Jul;55(1):106-11. doi: 10.1097/01.TA.0000071620.27375.BE.
- Background: PubMed 15659943Pelosi P, Severgnini P, Chiaranda M. An integrated approach to prevent and treat respiratory failure in brain-injured patients. Curr Opin Crit Care. 2005 Feb;11(1):37-42. doi: 10.1097/00075198-200502000-00006.
- Background: PubMed 25447937Garry PS, Ezra M, Rowland MJ, Westbrook J, Pattinson KT. The role of the nitric oxide pathway in brain injury and its treatment--from bench to bedside. Exp Neurol. 2015 Jan;263:235-43. doi: 10.1016/j.expneurol.2014.10.017. Epub 2014 Oct 29.
- Background: PubMed 23188422Terpolilli NA, Kim SW, Thal SC, Kuebler WM, Plesnila N. Inhaled nitric oxide reduces secondary brain damage after traumatic brain injury in mice. J Cereb Blood Flow Metab. 2013 Feb;33(2):311-8. doi: 10.1038/jcbfm.2012.176. Epub 2012 Nov 28.
- Background: PubMed 19222848Papadimos TJ, Medhkour A, Yermal S. Successful use of inhaled nitric oxide to decrease intracranial pressure in a patient with severe traumatic brain injury complicated by acute respiratory distress syndrome: a role for an anti-inflammatory mechanism? Scand J Trauma Resusc Emerg Med. 2009 Feb 17;17:5. doi: 10.1186/1757-7241-17-5.
- Background: PubMed 18272001Papadimos TJ. The beneficial effects of inhaled nitric oxide in patients with severe traumatic brain injury complicated by acute respiratory distress syndrome: a hypothesis. J Trauma Manag Outcomes. 2008 Jan 14;2(1):1. doi: 10.1186/1752-2897-2-1.
- Background: PubMed 11473859Vavilala MS, Roberts JS, Moore AE, Newell DW, Lam AM. The influence of inhaled nitric oxide on cerebral blood flow and metabolism in a child with traumatic brain injury. Anesth Analg. 2001 Aug;93(2):351-3 , 3rd contents page. doi: 10.1097/00000539-200108000-00023.
- Background: PubMed 9428538Dellinger RP, Zimmerman JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, Davis K Jr, Hyers TM, Papadakos P. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med. 1998 Jan;26(1):15-23. doi: 10.1097/00003246-199801000-00011.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Inhaled Nitric Oxide in people with Traumatic Brain Injury, run by University of Cincinnati at 1 site 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 3 inclusion and 11 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: finished, as of the sponsor's last update on 30 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 30 Apr 2025). 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?
PaO2 (time frame: at Day 3 of the study). 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 NCT03260569, which also lists 14 linked publications.
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 30 Apr 2025.