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

Shanghai Jiao Tong University

Status: Completed

Conditions: Brain Injuries; Craniocerebral Trauma

Treatments: Other: Normothermia; Other: Long-term mild hypothermia

Study type: Interventional

Funder types: Other

Identifiers

NCT01886222

RJNS001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 312 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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312 participants in 2 patient groups

Long-term mild hypothermia

Experimental group

Description:

Focused intervention

Treatment:

Other: Long-term mild hypothermia

Normothermia

Other group

Description:

Standard management

Treatment:

Other: Normothermia