Randomized Controlled Trial of Long-term Mild Hypothermia for Severe Traumatic Brain Injury (LTH-Ⅰ)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by RenJi Hospital
Sponsor:
Collaborators:
First Affiliated Hospital of Zhejiang University
West China Hospital
Second Affiliated Hospital of Wenzhou Medical University
The 101st Hospital of Chinese People's Liberation Army
The 98 Hospital of People's Liberation Army
Xuzhou Medical College
The second people's hospital of Shenzhen
The Second Affiliated Hospital of Kunming Medical University
The 94 Hospital of People's Liberation Army
Nanfang Hospital of Southern Medical University
The Affiliated Hospital of Medical College of Chinese People's Armed Police Forces
Xiangya Hospital of Central South University
First Affiliated Hospital of Fujian Medical University
The First People's Hospital of Taizhou, Zhejiang
Information provided by (Responsible Party):
Jiyao Jiang, RenJi Hospital
ClinicalTrials.gov Identifier:
NCT01886222
First received: June 17, 2013
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Brain Injuries
Craniocerebral Trauma
Other: Long-term mild hypothermia
Other: Normothermia
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by RenJi Hospital:

Primary Outcome Measures:
  • Neurological function [ Time Frame: 6 months post injury ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Intracranial pressure (ICP) control [ Time Frame: Admission, day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 14, or until the monitor is removed ] [ Designated as safety issue: No ]
    The effect of long-term hypothermia on ICP control will be determined.

  • Glasgow Coma Score (GCS) [ Time Frame: Admission, day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 14, day 21, day 28 post injury ] [ Designated as safety issue: No ]
    The neurological function improvement during study intervention will be evaluated.

  • Length of ICU stay [ Time Frame: 6 months post injury ] [ Designated as safety issue: No ]
    The numbers of days in the ICU.

  • Length of hospital stay [ Time Frame: 6 months post injury ] [ Designated as safety issue: No ]
    The numbers of days in the hospital.

  • Frequency of complications [ Time Frame: 6 months post injury ] [ Designated as safety issue: Yes ]
    Frequency of complications during the the study such as pneumonia, significant bleeding, liver and kidney function abnormality will be recorded and compared between groups.

  • Mortality rate [ Time Frame: 6 months post injury ] [ Designated as safety issue: No ]
    The proportion of death will be determined at 6 months post injury.


Estimated Enrollment: 300
Study Start Date: July 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Long-term mild hypothermia
Focused 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.
Other Name: Mild hypothermia therapy
Normothermia
Standard management
Other: Normothermia
Patients assigned to the normothermia group will be kept at 36-37℃.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01886222

Contacts
Contact: Guoyi Gao, MD, PhD 86-21-68383707 guoyigao@gmail.com

Locations
China, Shanghai
Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Recruiting
Shanghai, Shanghai, China, 200127
Contact: Guo Yi Gao, Dr.    86-21-68383707    guoyigao@gmail.com   
Contact: Jin Lei, Dr.    86-21-68383707    smiles1949@163.com   
Sponsors and Collaborators
RenJi Hospital
First Affiliated Hospital of Zhejiang University
West China Hospital
Second Affiliated Hospital of Wenzhou Medical University
The 101st Hospital of Chinese People's Liberation Army
The 98 Hospital of People's Liberation Army
Xuzhou Medical College
The second people's hospital of Shenzhen
The Second Affiliated Hospital of Kunming Medical University
The 94 Hospital of People's Liberation Army
Nanfang Hospital of Southern Medical University
The Affiliated Hospital of Medical College of Chinese People's Armed Police Forces
Xiangya Hospital of Central South University
First Affiliated Hospital of Fujian Medical University
The First People's Hospital of Taizhou, Zhejiang
Investigators
Principal Investigator: Jiyao Jiang, MD, PhD Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China
  More Information

Additional Information:
Publications:
Responsible Party: Jiyao Jiang, Professor, RenJi Hospital
ClinicalTrials.gov Identifier: NCT01886222     History of Changes
Other Study ID Numbers: RJNS001
Study First Received: June 17, 2013
Last Updated: January 21, 2014
Health Authority: China: Ethics Committee

Keywords provided by RenJi Hospital:
Traumatic brain injury

Additional relevant MeSH terms:
Craniocerebral Trauma
Hypothermia
Brain Injuries
Wounds and Injuries
Trauma, Nervous System
Nervous System Diseases
Body Temperature Changes
Signs and Symptoms
Brain Diseases
Central Nervous System Diseases

ClinicalTrials.gov processed this record on August 18, 2014