Trial Summaries

In Progress              

In Development              

Completed

 

 

In Progress:

BOOST III - Brain Oxygen Optimization in Severe TBI Phase III

PI: Ramon Diaz-Arrastia, MD, PhD - University of Pennsylvania

Status: Approved, preparing to enroll

Traumatic brain injury (TBI) is a major cause of death and disability. Of the 3.5 million Americans who sustain a TBI every year, approximately 27,000 experience prolonged traumatic coma, the most severe form of TBI. Less than 20% of these patients make a good recovery, and most are left with life-long disabilities. ICU management of severe TBI focuses on monitoring intracranial pressure (ICP), but data from recently conducted randomized clinical trials indicate that this approach is overly simplistic. Another approach is to monitor the partial pressure of oxygen in brain tissue (PbtO2), and apply interventions to prevent brain tissue hypoxia and improve neurologic outcome. Clinical studies demonstrate that brain tissue hypoxia is common, that there is a strong relationship between low PbtO2 and poor outcome, and that timely interventions can reverse brain tissue hypoxia. The first randomized controlled trial of PbtO2 monitoring in severe TBI, titled “Brain Oxygen Optimization in Severe TBI (BOOST) Phase 2,” enrolled 122 subjects, and demonstrated that the mean hypoxia burden was reduced by 74% by the treatment protocol informed by PbtO2 monitoring (p < 0.0001), and there were no significant safety issues. There was a trend towards improved functional outcome, supporting the pre-determined non-futility hypothesis. We are proposing the BOOST-3 trial to determine if there is evidence of clinical efficacy of a treatment protocol based on PbtO2 monitoring compared to treatment based on ICP monitoring alone. BOOST-3 will enroll patients with severe TBI requiring placement of ICP monitors within 6 hours of injury. Patients will be randomized to a treatment protocol based on ICP monitoring alone or the combination of ICP and PbtO2 monitoring. The Glasgow Outcome Scale-Extended (GOS-E) measured at 6 months post injury will be the primary outcome. Other secondary outcomes include functional, cognitive and behavioral assessments at 6 months, safety, survival to discharge, shortened time to follow commands, and reduction of total brain hypoxia exposure. 

 

HOBIT - Hyperbaric Oxygen Brain Injury Treatment Trial

PI: Gaylan L. Rockswold, MD - Hennepin County Medical Center

Status: Approved, preparing to enroll

Preclinical and clinical investigations (discussed below) strongly indicate that HBO2 is physiologically active in reducing brain injury and improving outcomes in severe TBI. However, prior to a definitive efficacy study, important information is required regarding optimizing the HBO treatment paradigm instituted in terms of pressure and frequency of HBO2 treatments 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 dose schedule 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.

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In Development:

ARCTIC - Acute Rapid Cooling for Therapy for Injuries of the Spinal Cord

PI: Michael Wang, MD, FACS - University of Miami

Status: In development

Synopsis

Traumatic spinal cord injury affects an estimated 11,000 people in the United States each year, most commonly affecting young adults in the prime of their life. Advances in the medical management of this patient population have resulted in improvements in the survivability of these injuries, with a majority of patients having a near-normal life expectancy. Thus, because of its devastating consequences but high likelihood of long-term survivability, exerts a disproportionate medical, social and economic toll. A great deal of research has been directed at identifying interventions which may mitigate the secondary mechanisms which lead to neurological worsening and impede native recovery. However, to date there have been no clinical trials definitively demonstrating the efficacy of acute interventions to improve neurological outcomes in humans with traumatic spinal cord injuries.

The SIREN-NETT network has proposed a randomized, controlled, multi-center study to investigate the efficacy of modest intravascular hypothermia (33.5 + 0.2° C) for improving neurological function following both complete and incomplete spinal cord injuries in humans. Significant improvement will be determined by a greater than 10 point difference between the two treatment arms in the mean change in motor score as determined at 12 month follow-up. Additional outcome measures will include ASIA sensory scores and measures of pain and disability. It is anticipated that such a study will answer the question of whether emergent intravascular cooling, a method which has shown promise in the laboratory, can improve the neurological function and independence of patients suffering from spinal cord injuries.

 

ICECAP - Influence of Cooling Duration On Efficacy in Cardiac Arrest Patients 

PI: Not assigned

Status: In development

Synopsis

Neurological death and disability are common outcomes in survivors of cardiac arrest. Therapeutic cooling of comatose patients resuscitated from shockable rhythyms has been shown in two randomized controlled trials to markedly increase the rate of good neurological outcome, but the optimal duration of induced hypothermia has not been investigated. ICECAP is a randomized adaptive clinical trial to characterize the duration‐response curve of induced hypothermia in comatose survivors of cardiac arrest and to determine the optimal duration of cooling. Subjects will initially be randomized to 12, 24, or 48 hours of cooling. After 150 subjects have been enrolled, response adaptive randomization will allocate subjects to a shorter duration (6 hours) if the developing model suggests a flat durationresponse curve, or to longer durations (60 or 72 hours) if the developing model suggests a positive but not yet plateauing duration‐response curve, and to the original and interposed durations (18, 30, 36, 42 hours) as needed to refine the model. Comatose adult survivors of cardiac arrest from shockable rythyms that have already been rapidly cooled using a definitive temperature control method (endovascular or surface) will be enrolled. The primary outcome will be modified Rankin score at 90 days analyzed as a weighted score incorporating both the proportion of subjects achieving a good neurological outcome and degree of residual functional impairment among those with good neurological outcomes.

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Completed:

Click here for all the completed SIREN-NETT trials.

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