Hyperbaric Oxygen Brain Injury Treatment Trial

Официальное название

Hyperbaric Oxygen Brain Injury Treatment (HOBIT) Trial

Обзор

The purpose of this innovative adaptive phase II trial design is to determine the optimal combination of hyperbaric oxygen treatment parameters that is most likely to demonstrate improvement in the outcome of severe TBI patients in a subsequent phase III trial.

Подробное описание

Preclinical and clinical investigations strongly indicate that hyperbaric oxygen (HBO2) is physiologically active in improving the destructive processes in severe Traumatic Brain Injury (TBI). However, prior to a definitive efficacy study, important information is required regarding optimizing the HBO2 treatment paradigm instituted in terms of pressure and whether NBH enhances the clinical effectiveness of the HBO2 treatment. Preclinical investigators working with TBI models have used pressures varying from 1.5 to 3.0 atmospheres absolute (ATA). Clinical investigators have used pressure varying from 1.5 to 2.5 ATA. However, the lungs in severe TBI patients have frequently been compromised by direct lung injury and/or acquired ventilator pneumonia and are susceptible to oxygen (O2) toxicity. Working within these constraints, it is essential to determine the most effective HBO2 treatment parameters without producing O2 toxicity and clinical complications. This proposed clinical trial is designed to answer these questions and to provide important data to plan a definitive efficacy trial.

Вмешательства

• Препарат Hyperbaric oxygen (1.5 ATA, no NBH)
  HBO at 1.5 ATA for 60 minutes without NBH. Treatment will be twice a day for five days or until patient is following commands or brain dead
• Препарат Hyperbaric oxygen (2.0 ATA, no NBH)
  HBO at 2.0 ATA for 60 minutes without NBH. Treatment will be twice a day for five days or until patient is following commands or brain dead
• Препарат Hyperbaric oxygen (2.5 ATA, no NBH)
  HBO at 2.5 ATA for 60 minutes without NBH. Treatment will be twice a day for five days or until patient is following commands or brain dead
• Препарат Hyperbaric oxygen (1.5 ATA + NBH)
  HBO at 1.5 ATA for 60 minutes followed by NBH for 3 hours. Treatment will be twice a day for five days or until patient is following commands or brain dead
• Препарат Hyperbaric oxygen (2.0 ATA + NBH)
  HBO at 2.0 ATA for 60 minutes followed by NBH for 3 hours. Treatment will be twice a day for five days or until patient is following commands or brain dead
• Препарат Hyperbaric oxygen (2.5 ATA + NBH)
  HBO at 2.5 ATA for 60 minutes followed by NBH for 3 hours. Treatment will be twice a day for five days or until patient is following commands or brain dead
• Препарат Normobaric Hyperoxia (NBH)
  100% fraction of inspired oxygen (FiO2) for 4.5 hours twice a day for five days or until patient following commands or brain dead
• Другое Usual Care
  Will be treated with usual and customary care for severe traumatic brain injury

Первичные конечные точки

• Glasgow Outcome Scale Extended (GOS-E) [Срок оценки: Assessment at 6 months]

Вторичные конечные точки (5)

• Duration of ICP elevation [Срок оценки: First 5 days]
• Therapeutic intensity level scores for controlling intracranial pressure (ICP) [Срок оценки: First 5 days]
• Brain tissue partial pressure of oxygen [Срок оценки: First 5 days]
• Serious adverse events [Срок оценки: 180 days]
• Peak brain tissue oxygen (P02) during HBO treatments [Срок оценки: First 5 days]

Критерии участия

Критерии включения

• Age 16 years or older and 65 years or younger
• Present with severe TBI, defined as Glasgow Coma Scale (GCS) of 3 to 8.
• Marshall computerized tomography (CT) score >1 in patients with a GCS of 7 or 8 or patients with an alcohol level >200 mg/dl
• Ability to initiate the first hyperbaric oxygen treatment within 8 hours of admission in patients not requiring a craniotomy/craniectomy or any other major surgical procedure OR
• Ability to initiate the first hyperbaric oxygen treatment within 14 hours of admission in patients requiring a craniotomy/craniectomy or major surgical procedure

Критерии исключения

• First hyperbaric oxygen treatment cannot be initiated within 24 hours of injury
• GCS of 3 with mid-position and non-reactive pupils bilaterally (4mm)
• Penetrating head injury
• Pregnant
• Pre-existing neurologic disease (e.g. TBI or stroke or neurodegenerative disorder) with confounding residual neurologic deficits
• Unstable acute spinal cord injury
• Fixed coagulopathy
• Severe hypoxia
• Cardiopulmonary resuscitation performed
• Coma suspected to de due to primarily non-TBI causes
• Any contraindications to the study intervention

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Факторный дизайн

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

США · 10 центров

• UCSD Medical Center - Hillcrest Hospital — San Diego
• St. Mary's Medical Center — West Palm Beach
• University of Iowa Hospitals and Clinics — Iowa City
• University of Kentucky Hospital — Lexington
• University of Maryland — Baltimore
• Detroit Receiving Hospital — Detroit
• Hennepin County Hospital — Minneapolis
• University of Nebraska Medical Center — Omaha
• … и ещё 2 центра

Канада · 1 центр

• Hamilton Heath Services — Hamilton

Публикации

• Rockswold SB, Rockswold GL, Zaun DA, Zhang X, Cerra CE, Bergman TA, Liu J. A prospective, randomized clinical trial to compare the effect of hyperbaric to normobaric hyperoxia on cerebral metabolism, intracranial pressure, and oxygen toxicity in severe traumatic brain injury. J Neurosurg. 2010 May;112(5):1080-94. doi: 10.3171/2009.7.JNS09363. PMID 19852540
• Rockswold SB, Rockswold GL, Zaun DA, Liu J. A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury. J Neurosurg. 2013 Jun;118(6):1317-28. doi: 10.3171/2013.2.JNS121468. Epub 2013 Mar 19. PMID 23510092
• Rahman MM, Saif MSI, Beall J, Martin RL, Rockswold GL, Barsan WG, Korley FK, Silbergleit R, Stevenson V, Gajewski B. A Bayesian model with seasonal effects for predicting accrual in clinical trials: Application to HOBIT and BOOST-3 trials for severe traumatic brain injury. Contemp Clin Trials Commun. 2025 Dec 5;48:101586. doi: 10.1016/j.conctc.2025.101586. eCollection 2025 Dec. PMID 41446562
• Bantis LE, Young KJ, Tsimikas JV, Mosier BR, Gajewski B, Yeatts S, Martin RL, Barsan W, Silbergleit R, Rockswold G, Korley FK. Statistical assessment of the prognostic and the predictive value of biomarkers-A biomarker assessment framework with applications to traumatic brain injury biomarker studies. Res Methods Med Health Sci. 2023 Jan;4(1):34-48. doi: 10.1177/26320843221141056. Epub 2022 Dec 13 PMID 37009524
• Wang Y, Yeatts SD, Martin RH, Silbergleit R, Rockswold GL, Barsan WG, Korley FK, Rockswold S, Gajewski BJ. Selection of a statistical analysis method for the Glasgow Outcome Scale-Extended endpoint for estimating the probability of favorable outcome in future severe TBI clinical trials. Stat Med. 2023 Nov 10;42(25):4582-4601. doi: 10.1002/sim.9877. Epub 2023 Aug 20. PMID 37599009
• Beall J, Yeatts SD, Silbergleit R, Shutter L, Korley F, Gajewski B. Bayesian enrollment modeling for several emergency medicine clinical trials. Trials. 2025 Nov 10;26(1):483. doi: 10.1186/s13063-025-08748-3. PMID 41214784
• Shi X, Wick JA, Martin RL, Beall J, Silbergleit R, Rockswold GL, Barsan WG, Korley FK, Rockswold S, Gajewski BJ. Improved mortality analysis in early-phase dose-ranging clinical trials for emergency medical diseases using Bayesian time-to-event models with active comparators. Stat Med. 2024 Aug 30;43(19):3649-3663. doi: 10.1002/sim.10141. Epub 2024 Jun 17. PMID 38885949
• Yeatts SD, Martin RH, Meurer W, Silbergleit R, Rockswold GL, Barsan WG, Korley FK, Wright DW, Gajewski BJ. Sliding Scoring of the Glasgow Outcome Scale-Extended as Primary Outcome in Traumatic Brain Injury Trials. J Neurotrauma. 2020 Dec 15;37(24):2674-2679. doi: 10.1089/neu.2019.6969. Epub 2020 Aug 26. PMID 32664792

Идентификаторы

NCT: NCT02407028 · GLR-NIH-2015

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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