Inhaled Nitric Oxide in Brain Injury

NCT03260569 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 2017 Goodman
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Traumatic Brain Injury

Keywords

Mechanical ventilation; Inhaled nitric oxide

Outcome Measures

Primary Outcomes (1)

• PaO2

  The primary endpoint is the difference in PO2

  at Day 3 of the study

Study Arms (2)

Inhaled Nitric Oxide

ACTIVE COMPARATOR

Inhaled nitric oxide at 20 parts per million, administered once during first 36 hours following admission

Drug: Inhaled Nitric Oxide

Placebo

PLACEBO COMPARATOR

Nitrogen only, administered once during first 36 hours following admission

Drug: Placebo

Interventions

Inhaled Nitric Oxide DRUG

Patients randomized to this arm will receive inhaled nitric oxide 20 parts per million.

Inhaled Nitric Oxide

Placebo DRUG

Nitrogen plus oxygen

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospital admission with traumatic brain injury (penetrating or blunt)
• Requirement for mechanical ventilation
• Glasgow Coma Score \> 3

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• University of Cincinnati: lead

Study Sites (1)

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Related Publications (13)

• 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.

  PMID: 420436 BACKGROUND

• Cooper 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.

  PMID: 6346942 BACKGROUND

• Koutsoukou 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.

  PMID: 17053881 BACKGROUND

• Gruber 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.

  PMID: 10199529 BACKGROUND

• Holland 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.

  PMID: 12855888 BACKGROUND

• Pelosi 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.

  PMID: 15659943 BACKGROUND

• Garry 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.

  PMID: 25447937 BACKGROUND

• Terpolilli 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.

  PMID: 23188422 BACKGROUND

• Papadimos 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.

  PMID: 19222848 BACKGROUND

• Papadimos 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.

  PMID: 18272001 BACKGROUND

• Vavilala 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.

  PMID: 11473859 BACKGROUND

• Dellinger 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.

  PMID: 9428538 BACKGROUND

• Lundin 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.

  PMID: 10501745 BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Results Point of Contact

• Title: Michael Goodman
• Organization: University of Cincinnati

michael.goodman@uc.edu

5135585661

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Both nitric oxide and placebo nitrogen will be made available in unmarked cylinders.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor

Model Details: 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.

Study Record Dates

• First Submitted: August 22, 2017
• First Posted: August 24, 2017
• Study Start: December 12, 2018
• Primary Completion: December 28, 2023
• Study Completion: December 28, 2023
• Last Updated: April 30, 2025
• Results First Posted: April 30, 2025

Record last verified: 2025-04

Locations

US (1)