Clinical trial NCT03163459: Short-duration Selective Brain Cooling for Patients Undergoing Mechanical Thrombectomy
Official title: Short-duration Selective Brain Cooling for Ischemic Stroke Patients Undergoing Mechanical Thrombectomy: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
PHASE3
Conditions: Hypothermia
Stroke, Acute
Keywords: mechanical thrombectomy
selective brain cooling
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2017-05-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine the efficacy and safety of short-duration intra-artery selective brain cooling in addition to mechanical thrombectomy in patients with acute ischemic stroke.

Detailed description: Acute ischemic stroke remains one of the leading causes of disability and death in both developed and developing countries. Using intravenous thrombolysis combined with intra-arterial therapy to recanalize occluded vessels in eligible patients is recommended by current guidelines. Five randomized clinical trials showed that modified thrombolysis in cerebral ischemia (mTICI) 2b/3 recanalization can be achieved in 59-88% of acute ischemic stroke patients with anterior circulation large artery occlusion，but only an average of 46% of patients have a favorable outcome (modified Rankin Scale score \[mRS\] 0-2). Therefore, new therapeutic strategies in addition to thrombectomy for acute ischemic stroke are urgently needed.

As early as 1987, Busto et al. found that lowering of the brain temperature by only a few degrees during ischemia confers a marked neuroprotective effect. Therapeutic hypothermia has been suggested to be the most potent neuroprotective strategy in recent years5，and a number of clinical studies in patients with acute cerebral infarction also showed that mild hypothermia (33-35 ℃) can increase tolerance to ischemic insults and play a significant neuroprotective role after reperfusion. However, adverse events such as pneumonia, affecting up to 35% of treated patients occurs with hypothermia. Since selective brain cooling does not require a reduction in core body temperature, it is theoretically possible to avoid many serious adverse effects caused by whole body hypothermia.

The investigators have previous shown that short-duration selective brain cooling by the intra-arterial infusion of cold saline combined with mechanical thrombectomy in acute ischemic stroke is feasible and safe. The efficacy of selective brain cooling in patients undergoing mechanical thrombectomy, however, is not established. The investigators therefore conducted this RCT study to explore the efficacy of short-duration selective brain cooling in patients with acute ischemic stroke who underwent mechanical thrombectomy.

Eligibility criteria: Inclusion Criteria:

* Acute ischemic stroke within 6 hours from symptom onset/last seen well.
* Occlusion (TIMI 0-1) of the basilar artery or distal intracranial carotid artery or middle (M1/M2) or anterior (A1/A2) cerebral artery as evidenced by CTA/MRA/DSA.
* Age ≥18 and ≤80
* No significant pre-stroke functional disability (mRS ≤ 1)
* The possibility to start treatment within 6 hours from onset.
* Informed consent given

Exclusion Criteria:

* Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR \> 3.0
* Baseline platelet count \< 50.000/µL
* Baseline blood glucose of \< 50mg/dL or \>400mg/dl
* Severe, sustained hypertension (SBP \> 220 mm Hg or DBP \> 110 mm Hg) NOTE: If the blood pressure can be successfully reduced and maintained below these levels using commonly used medications in China for these purposes (including iv antihypertensive drips), the patient can be enrolled.
* Serious, advanced, or terminal illness with anticipated life expectancy of less than one year.
* History of life threatening allergy (more than rash) to contrast medium
* Subjects who has received iv t-PA treatment beyond 4.5 hours from the beginning of the symptoms.
* Patients with acute stroke within the first 48 hours after percutaneous cardiac, cerebrovascular interventions and major surgery
* Renal insufficiency with creatinine ≥ 3 mg/dl
* Woman of childbearing potential who is known to be pregnant or lactating or who has a positive pregnancy test on admission.
* Subject participating in a study involving an investigational drug or device that would impact this study.
* Cerebral vasculitis
* Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be ≤ 1, which includes patients who are severely demented, require constant assistance in a nursing home type setting or who live at home but are not fully independent in activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.)
* Unlikely to be available for 90 days follow-up (e.g. no fixed home address, visitor from overseas).
* CT or MR evidence of hemorrhage (the presence of microbleeds on MRI is allowed).

Primary outcomes:
measure: Proportion of patients achieving favorable outcomes defined as mRS 0-2 at 90 days as evaluated by independent central assessors who are blinded to treatment
timeFrame: 90 days
Secondary outcomes:
measure: Dramatic early favorable response
timeFrame: 24 hours
measure: Final infarct volume evaluated on CT/MR at 24 hours (-2/+12 hours)
timeFrame: 24 hours
measure: The change of infarct volume compared with baseline.
timeFrame: 24 hours
measure: Vessel recanalization
timeFrame: 24 hours
measure: Barthel Index at 90 days
timeFrame: 90 days
measure: NIHSS at 90 days
timeFrame: 90 days
measure: Proportion of patients achieving excellent favorable outcomes defined as mRS 0-1 at 90 days
timeFrame: 90 days
measure: mRS shift analysis at 90 days
timeFrame: 90 days
Other outcomes:
measure: Mortality at 90 days
timeFrame: 90 days
measure: Clinically significant ICH rates at 24 (-2/+12) hours.
timeFrame: 24 hours
measure: Procedural related complications
timeFrame: From the operation to 24 hours after the operation
measure: Rectal temperature
timeFrame: From 1 hour before operation to 1 hours after operation
measure: Hematocrit
timeFrame: From 3 hour before operation to 3 hours after operation
measure: blood biochemistry
timeFrame: From 3 hour before operation to 3 hours after operation
measure: Vital signs
timeFrame: From 1 hour before operation to 24 hours after operation
Locations:
city: Beijing
country: China
facility: Xuan Wu Hospital，Capital Medical University
state: Beijing
Study officials:
References:
citation: Chen J, Liu L, Zhang H, Geng X, Jiao L, Li G, Coutinho JM, Ding Y, Liebeskind DS, Ji X. Endovascular Hypothermia in Acute Ischemic Stroke: Pilot Study of Selective Intra-Arterial Cold Saline Infusion. Stroke. 2016 Jul;47(7):1933-5. doi: 10.1161/STROKEAHA.116.012727. Epub 2016 May 19.