Brain InjuriesLTH-ⅠNCT01886222
Randomized Controlled Trial of Long-term Mild Hypothermia for Severe Traumatic Brain Injury
A study testing Long-term mild hypothermia and Normothermia in people with Brain Injuries and Craniocerebral Trauma, run by RenJi Hospital at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Brain Injuries, Craniocerebral Trauma
- What is being tested?
- Long-term mild hypothermia and Normothermia
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 312 participants
- Where
- 1 siteChina
- Study dates
- 12 Nov 2013to 30 Jun 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
China1 site
Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
Shanghai, Shanghai Municipality, 200127
About this study
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
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.
Read the 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.
- Conditions
- Brain Injuries, Craniocerebral Trauma
- Being tested
- Long-term mild hypothermia, Normothermia
- Keywords
- Traumatic brain injury
- Medical subject headings
- Brain Injuries, Craniocerebral Trauma, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Long-term mild hypothermiaOther
Also called Mild hypothermia therapy
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.
NormothermiaOther
Patients assigned to the normothermia group will be kept at 36-37℃.
| Study group | Role | What they receive |
|---|---|---|
| Long-term mild hypothermia | Experimental | Focused intervention Receives: Other: Long-term mild hypothermia |
| Normothermia | Other | Standard management Receives: Other: Normothermia |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months post injury
Secondary outcomes (6)
Intracranial pressure (ICP) control
The effect of long-term hypothermia on ICP control will be determined.
Measured: Admission, day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 14, or until the monitor is removed
Glasgow Coma Score (GCS)
The neurological function improvement during study intervention will be evaluated.
Measured: Admission, day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 14, day 21, day 28 post injury
Length of ICU stay
The numbers of days in the ICU.
Measured: 6 months post injury
Length of hospital stay
The numbers of days in the hospital.
Measured: 6 months post injury
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.
Measured: 6 months post injury
Mortality rate
The proportion of death will be determined at 6 months post injury.
Measured: 6 months post injury
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2013 (estimated)
- Study start12 Nov 2013
- Primary completion30 Jun 2019
- Study completion30 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Brain InjuriesStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 312 participants (actual)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- 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, Shenzhen Second People's Hospital, The 94 Hospital of People's Liberation Army, Nanfang Hospital, Southern Medical University, The Affiliated Hospital of Medical College of Chinese People's Armed Police Forces, Xiangya Hospital of Central South University, Taizhou First People's Hospital, Tang-Du Hospital, Qilu Hospital of Shandong University, Chongqing Emergency Medical Center, Xuzhou Central Hospital, The Affiliated Hospital Of Southwest Medical University
- Responsible party
- Principal investigator, Jiyao Jiang, RenJi Hospital
- Investigators
- Jiyao Jiang, MD, PhD, Principal investigator, Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01886222
- Sponsor's protocol ID
- RJNS001
- Acronym
- LTH-Ⅰ
- Status last verified
- Mar 2020
- First submitted
- 17 Jun 2013
- Last updated
- 13 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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. doi: 10.1038/sj.jcbfm.9600253.
PubMed 16306933Lei 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.
PubMed 25460339Hui J, Feng J, Tu Y, Zhang W, Zhong C, Liu M, Wang Y, Long L, Chen L, Liu J, Mou C, Qiu B, Huang X, Huang Q, Zhang N, Yang X, Yang C, Li L, Ma R, Wu X, Lei J, Jiang Y, Liu L, Gao G, Jiang J; LTH-1 Trial collaborators. Safety and efficacy of long-term mild hypothermia for severe traumatic brain injury with refractory intracranial hypertension (LTH-1): A multicenter randomized controlled trial. EClinicalMedicine. 2021 Jan 28;32:100732. doi: 10.1016/j.eclinm.2021.100732. eCollection 2021 Feb.
PubMed 33681741
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01886222
- Acronym / sponsor ID
- LTH-Ⅰ / RJNS001
- Conditions
- Brain Injuries, Craniocerebral Trauma
- Keywords
- Traumatic brain injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 312 participants (actual)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- 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, Shenzhen Second People's Hospital, The 94 Hospital of People's Liberation Army, Nanfang Hospital, Southern Medical University, The Affiliated Hospital of Medical College of Chinese People's Armed Police Forces, Xiangya Hospital of Central South University, Taizhou First People's Hospital, Tang-Du Hospital, Qilu Hospital of Shandong University, Chongqing Emergency Medical Center, Xuzhou Central Hospital, The Affiliated Hospital Of Southwest Medical University
- Study start
- 12 Nov 2013 (actual)
- Primary completion
- 30 Jun 2019 (actual)
- Study completion
- 30 Jun 2019 (actual)
- First posted
- 25 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Long-term mild hypothermia | Experimental | Other: Long-term mild hypothermiaFocused intervention |
| Normothermia | Other | Other: NormothermiaStandard management |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Long-term mild hypothermiaAlso: Mild hypothermia therapyHypothermia 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 | Long-term mild hypothermia |
| NormothermiaPatients assigned to the normothermia group will be kept at 36-37℃. | Other | Normothermia |
Primary outcome
Neurological function
Time frame: 6 months post injury
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 secondary outcomes
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
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
Length of ICU stay
Time frame: 6 months post injury
Length of hospital stay
Time frame: 6 months post injury
Frequency of complications
Time frame: 6 months post injury
Mortality rate
Time frame: 6 months post injury
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Background: PubMed 16306933Jiang 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. doi: 10.1038/sj.jcbfm.9600253.
- Background: PubMed 25460339Lei 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.
- Derived from this study: PubMed 33681741Hui J, Feng J, Tu Y, Zhang W, Zhong C, Liu M, Wang Y, Long L, Chen L, Liu J, Mou C, Qiu B, Huang X, Huang Q, Zhang N, Yang X, Yang C, Li L, Ma R, Wu X, Lei J, Jiang Y, Liu L, Gao G, Jiang J; LTH-1 Trial collaborators. Safety and efficacy of long-term mild hypothermia for severe traumatic brain injury with refractory intracranial hypertension (LTH-1): A multicenter randomized controlled trial. EClinicalMedicine. 2021 Jan 28;32:100732. doi: 10.1016/j.eclinm.2021.100732. eCollection 2021 Feb.
- Ren Ji Hospital is one of the top medical centers across China.Link provided by the sponsor.
- Prof. Jiang holds the title of Chairman of International Neurotrauma Society.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jiyao Jiang, MD, PhD principal investigator
Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Long-term mild hypothermia and Normothermia in people with Brain Injuries and Craniocerebral Trauma, run by RenJi Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurological function (time frame: 6 months post injury). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01886222, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.