Randomized Controlled Trial of Long-term Mild Hypothermia for Severe Traumatic Brain Injury

Brain Injuries Clinical Trial

— LTH-?  

Official title:

A Multi-center, Randomized, Controlled Trial to Evaluate the Efficacy and Safety of Long-term Mild Hypothermia in Adult Patients With Severe Traumatic Brain Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01886222
• Other study ID #: RJNS001
• Status: Completed
• Phase: N/A
• Start date: November 12, 2013
• Est. completion date: June 30, 2019

Study information

• Verified date: March 2020
• Source: RenJi Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a prospective multi-centre randomized trial to compare the effect of long-term mild hypothermia versus routine normothermic intensive management in patients with severe traumatic brain injury.

The primary hypothesis is that the induction of mild hypothermia (maintained at 34-35℃) for 5 days will improve the outcome of patients at six months post injury compared with normothermia.

Description:

Traumatic brain injury (TBI) remains a leading cause of death and disability in people with injuries and constitutes a major public health concern both in developed and developing countries. There are multiple clinical trials of hypothermia therapy for TBI conducted, however, with conflicting results. Subgroup analysis of most meta-analysis showed that therapeutic effect was significant when hypothermia was maintained more than 48 hours. We have previously reported a multicenter trial of mild hypothermia (33-35℃) for severe traumatic brain injury, in which 215 patients was randomized to long-term mild hypothermia group (n = 108) for 5 ±1.3 days mild hypothermia therapy and short-term mild hypothermia group ( n = 107) for 2±0.6 days mild hypothermia therapy. The results shown improved outcomes in patients with long-term mild hypothermia and similar frequency of complications. Therefore we concluded that long-term hypothermia, which maintains at 33-35℃ for 5 days, could be considered in the management of severe traumatic brain injury.

Hypothermia therapy was recommend as the level III evidence by the 2007 Brain Trauma Foundation's guideline and this treatment is currently used in our department and other large neurosurgical centers across China, with the aim to decrease the high intracranial pressure (ICP) and improve the functional outcome of TBI patients. When the decision was made, the injured patients would be placed on cooling blankets, tracheotomized and ventilated. The patients would receive continuous infusions of a paralytic drug (Tracrium 10-40 mg/hour) and chlorpromazine (5-10 mg/hour) administered using an infusion pump to prevent shivering. The dosage was given according to each patient's temperature, blood pressure, heart rate, and muscular tone. Once the patient's rectal temperature reached 33˚C, it was kept at approximately that temperature (33-35˚C) 5 to 7 days. Then the patients were passively rewarmed to a temperature of 37 to 38˚C at a rate no greater than 1˚C/hour, by gradual adjustment of the blanket thermostat.

The present multi-center, randomized controlled trials is designed to investigate the efficacy and safety of long-term (5 days) mild hypothermia versus normothermia on the outcome of patients following severe traumatic brain injury. The primary outcome is the neurological function assessed at 1, 6 months post injury with the Glasgow Outcome Score (GOS). Additionally, the following data will also be recorded and compared: the baseline data, Glasgow Coma Score,imaging examination (e.g. CT scan), need of surgery, intracranial pressure, laboratory tests (e.g. blood routine test, liver and kidney function, blood gas analysis, etc), the complications (e.g. pneumonia, significant bleeding) and so on.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 312
• Est. completion date: June 30, 2019
• Est. primary completion date: June 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age 18 - 65 years within 6 hours post injury;

• Closed head injury;

• Glasgow Coma Scale(GCS) score 4 to 8 after resuscitation;

• The intracranial pressure is more than 25 mmHg;

• Cerebral contusion on computed tomographic scan.

Exclusion Criteria:

• GCS of 3 with bilateral fixed and dilated pupils;

• A life-threatening injury to an organ other than the brain;

• No spontaneous breathing or cardiac arrest at the scene of the injury;

• No consent;

• Pregnancy.

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Craniocerebral Trauma
• Hypothermia
• Wounds and Injuries

Intervention

Other:
• Long-term mild hypothermia
Hypothermia will be induced within 6 hours of injury and maintained at 34-35? for 5 days.Then the patients will be passively rewarmed to a temperature of 36 to 37°C at a rate no greater than 0.5°C/4 hours.
• Normothermia
Patients assigned to the normothermia group will be kept at 36-37?.

Locations

Country	Name	City	State
China	Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University	Shanghai	Shanghai

Sponsors (17)

Lead Sponsor

Collaborator

RenJi Hospital

Chongqing Emergency Medical Center, First Affiliated Hospital of Zhejiang University, Nanfang Hospital of Southern Medical University, Qilu Hospital of Shandong University, Second Affiliated Hospital of Wenzhou Medical University, Shenzhen Second People's Hospital, Tang-Du Hospital, The 101st Hospital of Chinese People's Liberation Army, The 94 Hospital of People's Liberation Army, The 98 Hospital of People's Liberation Army, The Affiliated Hospital of Medical College of Chinese People's Armed Police Forces, The Affiliated Hospital Of Southwest Medical University, The First People's Hospital of Taizhou, Zhejiang, West China Hospital, Xiangya Hospital of Central South University, Xuzhou Central Hospital

Country where clinical trial is conducted

China, 

References & Publications (2)

Jiang JY, Xu W, Li WP, Gao GY, Bao YH, Liang YM, Luo QZ. Effect of long-term mild hypothermia or short-term mild hypothermia on outcome of patients with severe traumatic brain injury. J Cereb Blood Flow Metab. 2006 Jun;26(6):771-6. — View Citation

Lei J, Gao G, Mao Q, Feng J, Wang L, You W, Jiang J; LTH-1 trial collaborators. 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). Contemp Clin Trials. 2015 Jan;40:9-14. doi: 10.1016/j.cct.2014.11.008. Epub 2014 Nov 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurological function	The neurological function will be evaluated at 6 months post injury by a specialized investigator who is unaware of the patients' allocation according to five-category Glasgow Outcome Scale as follows: 1, death; 2, vegetative state - unable to interact with the environment; 3, severe disability - unable to live independently but able to follow commands; 4, moderate disability - capable of living independently but unable to return to work or school; and 5, good recovery - able to return to work or school.	6 months post injury
Secondary	Intracranial pressure (ICP) control	The effect of long-term hypothermia on ICP control will be determined.	Admission, day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 14, or until the monitor is removed
Secondary	Glasgow Coma Score (GCS)	The neurological function improvement during study intervention will be evaluated.	Admission, day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 14, day 21, day 28 post injury
Secondary	Length of ICU stay	The numbers of days in the ICU.	6 months post injury
Secondary	Length of hospital stay	The numbers of days in the hospital.	6 months post injury
Secondary	Frequency of complications	Frequency of complications during the the study such as pneumonia, significant bleeding, liver and kidney function abnormality will be recorded and compared between groups.	6 months post injury
Secondary	Mortality rate	The proportion of death will be determined at 6 months post injury.	6 months post injury

External Links

•   Prof. Jiang holds the title of Chairman of International Neurotrauma Society.
•   Ren Ji Hospital is one of the top medical centers across China.
•   Shanghai Institute of Head Trauma leads the research on neurotrauma nationally and has made a lot of effort in traumatic brain injury.