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

A 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

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.

Study Overview

• Status: Unknown
• Conditions: Hypothermia; Aneurysmal Subarachnoid Hemorrhage
• Intervention / Treatment: Procedure: Zoll 2000 and/or CureWrap 3500 cooling system

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 32˚C, it was kept at approximately that temperature (32-35˚C) 3 to 7 days. Then the patients were passively rewarmed to a temperature of 36 to 37˚C at a rate no greater than 0.25˚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 (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 Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xin Qu, MD,PhD; Phone Number: 86-10-83198633; Email: xinqu0213@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological function	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.	6 months after hemorrhage

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial pressure	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, until the monitor is removed
Length of ICU stay	The numbers of days in the ICU	6 months post hemorrhage
Length of hospital stay	The numbers of days in the hospital.	6 months post hemorrhage
Frequency of complications	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.	6 months post hemorrhage
Mortality rate	The proportion of death will be determined	6 months after hemorrhage

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Collaborators: Beijing Tiantan Hospital; Qilu Hospital of Shandong University; Second Affiliated Hospital, School of Medicine, Zhejiang University; First Affiliated Hospital of Fujian Medical University; Shandong Provincial Hospital; The First Hospital of Jilin University; Central South University; Tang-Du Hospital; First Affiliated Hospital of Wenzhou Medical University; The First Affiliated Hospital of Dalian Medical University; First Affiliated Hospital of Harbin Medical University; Yantai Yuhuangding Hospital; Shanxi Cardiovascular Hospital
• Investigators: Principal Investigator: Ning Wang, MD,PhD, Xuanwu Hospital,Capital Medical University, Beijing

Publications and helpful links

General Publications

• Seule MA, Muroi C, Mink S, Yonekawa Y, Keller E. Therapeutic hypothermia in patients with aneurysmal subarachnoid hemorrhage, refractory intracranial hypertension, or cerebral vasospasm. Neurosurgery. 2009 Jan;64(1):86-92; discussion 92-3. doi: 10.1227/01.NEU.0000336312.32773.A0.
• Qu X, Shang F, Zhao H, Qi M, Cheng W, Xu Y, Jiang L, Chen W, Wang N, Zhang H. Targeted temperature management at 33 degrees Celsius in patients with high-grade aneurysmal subarachnoid hemorrhage: a protocol for a multicenter randomized controlled study. Ann Transl Med. 2021 Apr;9(7):581. doi: 10.21037/atm-20-4719.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2018
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: January 16, 2018
• First Submitted That Met QC Criteria: February 15, 2018
• First Posted (Actual): February 22, 2018

Study Record Updates

• Last Update Posted (Actual): February 26, 2018
• Last Update Submitted That Met QC Criteria: February 23, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Body Temperature Changes; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage; Hypothermia
• Other Study ID Numbers: LTHSAH-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No