Beta blocker use in traumatic brain injury based on the high-sensitive troponin status (BBTBBT): methodology and protocol implementation of a double-blind randomized controlled clinical trial

Hassan Al-Thani,Sandro Rizoli,Abdulnasser Alyafai,Ruben Peralta,Ayman El-Menyar,Ahmed Abdel-Aziz Bahey,Husham Abdelrahman,Mohammad Asim,Talat Chughtai

doi:10.1186/s13063-021-05872-8

Abstract

BackgroundBeta-adrenergic receptor blockers (BB) play an important role in the protection of organs that are susceptible for secondary injury due to stress-induced adrenergic surge. However, the use of BB in traumatic brain injury (TBI) patients is not yet the standard of care which necessitates clear scientific evidence to be used. The BBTBBT study aims to determine whether early administration of propranolol based on the high-sensitive troponin T(HsTnT) status will improve the outcome of TBI patients. We hypothesized that early propranolol use is effective in reducing 10- and 30-day mortality in TBI patients. Secondary outcomes will include correlation between serum biomarkers (troponin, epinephrine, cytokines, enolase, S100 calcium binding protein B) and the severity of injury and the impact of BB use on the duration of hospital stay and functional status at a 3-month period.MethodsThe BBTBBT study is a prospective, randomized, double-blinded, placebo-controlled three-arm trial of BB use in mild-to-severe TBI patients based on the HsTnT status. All enrolled patients will be tested for HsTnT at the first 4 and 6 h post-injury. Patients with positive HsTnT will receive BB if there is no contraindication (group 1). Patients with negative HsTnT will be randomized to receive either propranolol (group 2) or placebo (group 3). The time widow for receiving the study treatment is the first 24 h post-injury.DiscussionEarly BB use may reduce the catecholamine storm and subsequently the cascade of immune and inflammatory changes associated with TBI. HsTnT could be a useful fast diagnostic and prognostic tool in TBI patients. This study will be of great clinical interest to improve survival and functional outcomes of TBI patients.Trial registrationClinicalTrials.gov NCT04508244. Registered on 7 August 2020. Recruitment started on 29 December 2020 and is ongoing.

Highlights

Traumatic brain injury (TBI) accounts for up to 30% of all injury-related deaths [1]
Methods and study design The Beta Blocker Use in Traumatic Brain Injury Based on the High-Sensitive Troponin T Status (BBTBBT) is a prospective double-blind randomized controlled trial (RCT) of Beta-adrenergic receptor blockers (BB) use in traumatic brain injury (TBI) patients based on the high-sensitive troponin T (TnT) (HsTnT) status
Statistical analysis plan The proposed sample size is based on an estimated rate of 12% reduction in mortality with the use of BBs in TBI patients reported by Salim et al [13], having 80% power and 5% alpha error; the estimated sample size would be 257 subjects in each study group

Summary

Methods

The BBTBBT study is a prospective, randomized, double-blinded, placebo-controlled three-arm trial of BB use in mild-to-severe TBI patients based on the HsTnT status. All enrolled patients will be tested for HsTnT at the first 4 and 6 h post-injury. Patients with positive HsTnT will receive BB if there is no contraindication (group 1). Patients with negative HsTnT will be randomized to receive either propranolol (group 2) or placebo (group 3). The time widow for receiving the study treatment is the first 24 h post-injury

Discussion

Introduction

Findings