Key result
The EBB-TBI study is a planned phase 2a dose-finding trial designed to determine the maximum tolerated dosing schedule for early intravenous esmolol in adults with severe traumatic brain injury.
Why the study?
Beta-blockade may benefit severe traumatic brain injury by reducing catecholamines, but practical advantages must be balanced against the risk of hypotension.
Does early intravenous esmolol infusion achieve a clinically significant reduction in heart rate while maintaining cerebral perfusion pressure in adults with severe traumatic brain injury?
Does early intravenous esmolol infusion achieve a clinically significant reduction in heart rate while maintaining cerebral perfusion pressure in adults with severe traumatic brain injury?
This protocol outlines a Phase 2a dose-finding study to determine the optimal esmolol infusion schedule for heart rate reduction without compromising cerebral perfusion pressure in adults with severe traumatic brain injury.
Traumatic brain injury is a leading cause of death and disability worldwide. Interventions that mitigate secondary brain injury have the potential to improve outcomes for patients and reduce the impact on communities and society. Increased circulating catecholamines are associated with worse outcomes and there are supportive animal data and indications in human studies of benefit from beta-blockade after severe traumatic brain injury. Here, we present the protocol for a dose-finding study using esmolol in adults commenced within 24 h of severe traumatic brain injury. Esmolol has practical advantages and theoretical benefits as a neuroprotective agent in this setting, but these must be balanced against the known risk of secondary injury from hypotension. The aim of this study is to determine a dose schedule for esmolol, using the continual reassessment method, that combines a clinically significant reduction in heart rate as a surrogate for catecholamine drive with maintenance of cerebral perfusion pressure. The maximum tolerated dosing schedule for esmolol can then be tested for patient benefit in subsequent randomized controlled trials.Trial registration ISRCTN, ISRCTN11038397, registered retrospectively 07/01/2021 https://www.isrctn.com/ISRCTN11038397.
No takes yet. Share an insight, caveat, or question.
Thomas et al. (2023) studied Severe Traumatic Brain Injury (n=24). Esmolol was evaluated on Maximum tolerated dosage escalation schedule for esmolol combining ≥15% heart rate reduction with maintenance of cerebral perfusion pressure. The EBB-TBI study is a planned phase 2a dose-finding trial designed to determine the maximum tolerated dosing schedule for early intravenous esmolol in adults with severe traumatic brain injury.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: