title: 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
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Shanghai Institute of Head Trauma, Shanghai, People's Republic of China; Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People's Republic of China. Electronic address: doctorjinlei@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Lei
authors.affiliation: Shanghai Institute of Head Trauma, Shanghai, People's Republic of China; Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People's Republic of China. Electronic address: guoyigao@gmail.com.
authors.forename: Guoyi
authors.initials: G
authors.lastname: Gao
authors.affiliation: Shanghai Institute of Head Trauma, Shanghai, People's Republic of China; Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People's Republic of China. Electronic address: maoq@netease.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Shanghai Institute of Head Trauma, Shanghai, People's Republic of China; Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People's Republic of China. Electronic address: fengjfmail@163.com.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Feng
authors.affiliation: Shanghai Institute of Head Trauma, Shanghai, People's Republic of China; Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People's Republic of China. Electronic address: dldtshwl@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Head Trauma, Shanghai, People's Republic of China; Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People's Republic of China. Electronic address: smiles1949@163.com.
authors.forename: Wendong
authors.initials: W
authors.lastname: You
authors.affiliation: Shanghai Institute of Head Trauma, Shanghai, People's Republic of China; Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People's Republic of China. Electronic address: jiyaojiangrenji@126.com.
authors.forename: Jiyao
authors.initials: J
authors.lastname: Jiang
mesh_terms: D001831:Body Temperature; D001930:Brain Injuries / Q000628:therapy*; D002681:China; D002985:Clinical Protocols; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D007427:Intracranial Pressure; D007902:Length of Stay; D008297:Male; D011446:Prospective Studies; D012107:Research Design
keywords: Efficacy; Long-term mild hypothermia; Multicenter randomized trial; Safety; Severe traumatic brain injury