Clinical trial NCT03442608: Trial of Long-term Therapeutic Hypothermia for Poor-grade Aneurysmal Subarachnoid Hemorrhage
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hypothermia
Aneurysmal Subarachnoid Hemorrhage
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Fujian Medical University
name: Central South University
name: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Tang-Du Hospital
name: First Affiliated Hospital of Harbin Medical University
name: The First Hospital of Jilin University
name: The First Affiliated Hospital of Dalian Medical University
name: Shanxi Cardiovascular Hospital
name: Qilu Hospital of Shandong University
name: First Affiliated Hospital of Wenzhou Medical University
name: Shandong Provincial Hospital
name: Yantai Yuhuangding Hospital
name: Beijing Tiantan Hospital
First posted: 2018-02-22
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

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.

Primary outcomes:
measure: Neurological function
timeFrame: 6 months after hemorrhage
Secondary outcomes:
measure: Intracranial pressure
timeFrame: Admission, day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 14, until the monitor is removed
measure: Length of ICU stay
timeFrame: 6 months post hemorrhage
measure: Length of hospital stay
timeFrame: 6 months post hemorrhage
measure: Frequency of complications
timeFrame: 6 months post hemorrhage
measure: Mortality rate
timeFrame: 6 months after hemorrhage
Other outcomes:
Locations:
Study officials:
affiliation: Xuanwu Hospital,Capital Medical University, Beijing
name: Ning Wang, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.