Rationale, methodology, and implementation of a nationwide multicenter randomized controlled trial of long-term mild hypothermia for severe traumatic brain injury (the LTH-1 trial)

Abstract

Background: Traumatic brain injury (TBI) is a major public health problem recently, however, no intervention showing convincing efficacy. Therapeutic hypothermia with a relatively long duration (more than 48 h), as a promising treatment measure, might improve the patient outcome following severe TBI.

Methods/design: The LTH-1 trial is a prospective, nationwide multicenter, randomized, controlled clinical trial to examine the efficacy and safety of long-term mild hypothermia in adult patients after severe traumatic brain injury. A total of 300 consecutive patients will be recruited from 15 large neurosurgical centers in China. The eligible patient will be randomized to receive either long-term mild hypothermia (34-35 °C) for 5 days, or normothermia (36-37 °C). Additionally, a standardized management protocol will be used in all patients. The primary end point is the neurological outcome 6 months post-injury on the Glasgow Outcome Scale. The secondary outcomes include GOS score at one month post-injury, mortality during six months after injury, length of ICU and hospital stay, intracranial pressure control and Glasgow Coma Scale score during the hospital stay and frequency of complications during the six-month follow-up period.

Discussion: Long-term hypothermia is recommended by most recent studies and its efficacy urgently needs to be established in randomized controlled settings. The LTH-1 trial, together with other ongoing studies, will present more evidence for optimal use of hypothermia in severe TBI patients.

Keywords: Efficacy; Long-term mild hypothermia; Multicenter randomized trial; Safety; Severe traumatic brain injury.