Trial of Long-term Therapeutic Hypothermia for Poor-grade Aneurysmal Subarachnoid Hemorrhage

ID: NCT03442608
Status: Not yet recruiting
Phase: N/A
Start Date: March 01, 2018
First Submitted: January 16, 2018
Last Updated: February 23, 2018
Results: N/A
Sponsors & Collaborators: Xuanwu Hospital, Beijing, First Affiliated Hospital of Fujian Medical University, Central South University, Second Affiliated Hospital and 12 more..
Location: N/A
Conditions: Hypothermia, Aneurysmal Subarachnoid Hemorrhage
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Study Description

Brief Summary

This study is a prospective, multi-centre, randomized,controlled trial to compare the efficacy of long-term mild hypothermia with normothermic intensive management in patients with poor-grade aneurysmal subarachnoid hemorrhage.

The primary hypothesis is that the induction of mild hypothermia (maintained at 32-35℃) for at least 5 days would improve the outcome of patients at six months post hemorrhage compared with normothermia.

Detailed Description

Aneurysmal subarachnoid hemorrhage (aSAH), especially poor-grade aSAH, is a medical emergency with very high morbidity and mortality rates. SAH constitutes a major public health concern in developed and developing countries. There were several clinical trials of hypothermia for aSAH conducted, however, with conflicting results.

Hypothermia therapy treatment is currently used in our department and other large neurosurgical centers across China to decrease the intracranial pressure (ICP), mitigate some of the destructive processes, and improve the functional outcome of patients with poor-grade aSAH. When the decision was made, the patients would be placed in wrapped cooling blankets or intravascular cooling device after they were sedated, intubated and mechanically ventilated. The patients would receive continuous infusions of some drugs using an infusion pump to prevent shivering. Once the patient's rectal, nasopharyngeal or blood temperature reached 32ËšC, it was kept at approximately that temperature (32-35ËšC) 3 to 7 days. Then the patients were passively rewarmed to a temperature of 36 to 37ËšC at a rate no greater than 0.25ËšC/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 (3 days) mild hypothermia versus normothermia on the outcome of patients with poor-grade aSAH. The primary outcome is the neurological function assessed at 1,3, 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), 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.
Condition or disease Intervention/treatment Phase

Aneurysmal Subarachnoid Hemorrhage

Hypothermia

Procedure: Zoll 2000 and/or CureWrap 3500 cooling system
Other Names
N/A

Tracking Information

First Submitted DateJanuary 16, 2018
Last Update Posted DateFebruary 23, 2018
Anticipated Start DateMarch 01, 2018
Anticipated Completion DateDecember 31, 2020
Anticipated Primary Completion DateDecember 31, 2020
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Neurological function [Time Frame: 6 months after hemorrhage]

    The neurological function will be evaluated at 6 months after hemorrhage by 2 specialized investigators who are 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.

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Intracranial pressure [Time Frame: Admission, day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 14, until the monitor is removed]

    The effect of long-term hypothermia on ICP control will be determined.

  • Length of ICU stay [Time Frame: 6 months post hemorrhage]

    The numbers of days in the ICU

  • Length of hospital stay [Time Frame: 6 months post hemorrhage]

    The numbers of days in the hospital.

  • Frequency of complications [Time Frame: 6 months post hemorrhage]

    Frequency of complications during the the study such as pneumonia, coagulation disturbance,electrolyte disturbances, liver and kidney function abnormality will be recorded and compared between groups.

  • Mortality rate [Time Frame: 6 months after hemorrhage]

    The proportion of death will be determined

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleTrial of Long-term Therapeutic Hypothermia for Poor-grade Aneurysmal Subarachnoid Hemorrhage
Official TitleA Multi-center, Randomized, Controlled Trial to Investigate the Efficacy and Safety of Long-term Therapeutic Hypothermia in Adult Patients With Poor-grade Aneurysmal Subarachnoid Hemorrhage
Brief Summary

This study is a prospective, multi-centre, randomized,controlled trial to compare the efficacy of long-term mild hypothermia with normothermic intensive management in patients with poor-grade aneurysmal subarachnoid hemorrhage.

The primary hypothesis is that the induction of mild hypothermia (maintained at 32-35℃) for at least 5 days would improve the outcome of patients at six months post hemorrhage compared with normothermia.

Detailed Description

Aneurysmal subarachnoid hemorrhage (aSAH), especially poor-grade aSAH, is a medical emergency with very high morbidity and mortality rates. SAH constitutes a major public health concern in developed and developing countries. There were several clinical trials of hypothermia for aSAH conducted, however, with conflicting results.

Hypothermia therapy treatment is currently used in our department and other large neurosurgical centers across China to decrease the intracranial pressure (ICP), mitigate some of the destructive processes, and improve the functional outcome of patients with poor-grade aSAH. When the decision was made, the patients would be placed in wrapped cooling blankets or intravascular cooling device after they were sedated, intubated and mechanically ventilated. The patients would receive continuous infusions of some drugs using an infusion pump to prevent shivering. Once the patient's rectal, nasopharyngeal or blood temperature reached 32ËšC, it was kept at approximately that temperature (32-35ËšC) 3 to 7 days. Then the patients were passively rewarmed to a temperature of 36 to 37ËšC at a rate no greater than 0.25ËšC/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 (3 days) mild hypothermia versus normothermia on the outcome of patients with poor-grade aSAH. The primary outcome is the neurological function assessed at 1,3, 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), 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 TypeInterventional
Study PhaseN/A
Estimated Enrollment
200
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Double
Primary Purpose
Treatment
Conditions
Aneurysmal Subarachnoid Hemorrhage
Hypothermia
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Procedure: Zoll 2000 and/or CureWrap 3500 cooling system

Device(Zoll 2000 and/or CureWrap 3500 cooling system),lasting 5 to 7 days, the core temperature will be controlled in 33-35 degree.

Other Names
Study Groups/Cohorts
mild hypothermia
Device: Zoll 2000 and/or CureWrap 3500 cooling system,lasting 5 to 7 days, the core temperature will be controlled in 33-35 degree.

northermia
normal physical cooling methods,like ice bag, conditionally required.

Study Arms
Experimental mild hypothermia
Device: Zoll 2000 and/or CureWrap 3500 cooling system,lasting 5 to 7 days, the core temperature will be controlled in 33-35 degree.
Procedure : Zoll 2000 and/or CureWrap 3500 cooling system
Device(Zoll 2000 and/or CureWrap 3500 cooling system),lasting 5 to 7 days, the core temperature will be controlled in 33-35 degree.

Placebo Comparator northermia
normal physical cooling methods,like ice bag, conditionally required.
Procedure : Zoll 2000 and/or CureWrap 3500 cooling system
Device(Zoll 2000 and/or CureWrap 3500 cooling system),lasting 5 to 7 days, the core temperature will be controlled in 33-35 degree.

Arm Intervention/Treatment
Experimental mild hypothermia
Device: Zoll 2000 and/or CureWrap 3500 cooling system,lasting 5 to 7 days, the core temperature will be controlled in 33-35 degree.
Procedure : Zoll 2000 and/or CureWrap 3500 cooling system
Placebo Comparator northermia
normal physical cooling methods,like ice bag, conditionally required.
Procedure : Zoll 2000 and/or CureWrap 3500 cooling system

Recruitment Information

Recruitment Status:Not yet recruiting
Enrollment200
Completion DateDecember 31, 2020
Eligibility Criteria: Inclusion Criteria:
- Age 18 - 65 years within 72 hours after subarachnoid hemorrhage;
- Neurosurgical clipping or coiling for aneurysm;
- Hunt-Hess IV-V scale;
- The intracranial pressure is more than 20 mmHg.

Exclusion Criteria:
- GCS of 3 with bilateral fixed and dilated pupils;
- No spontaneous breathing or cardiac arrest at the scene of hemorrhage;
- No consent;
- Pregnancy.
GenderAll
Age18 Years to 65 Years
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Not Available

Administrative Information

NCT Number:NCT03442608
Other Study ID Numbers
LTHSAH-1
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible PartyNing Wang, Xuanwu Hospital, Beijing
Study Sponsor
Xuanwu Hospital, Beijing
Collaborators
First Affiliated Hospital of Fujian Medical University
Central South University
Second Affiliated Hospital, School of Medicine, Zhejiang University
Tang-Du Hospital
First Affiliated Hospital of Harbin Medical University
First Hospital of Jilin University
The First Affiliated Hospital of Dalian Medical University
Shanxi Province Cardiovascular Hospital
Qilu Hospital of Shandong University
First Affiliated Hospital of Wenzhou Medical Univeristy
Shandong Provincial Hospital
Yantai Yuhuangding Hospital
Beijing Tiantan Hospital
Investigators
Principal Investigator
Ning Wang, MD,PhD
Xuanwu Hospital,Capital Medical University, Beijing