Back to resultsShort-duration Selective Brain Cooling for Patients Undergoing Mechanical Thrombectomy
Primary Purpose
Hypothermia, Stroke, Acute
Status
Suspended
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
selective brain cooling by cold saline perfusion
mechanical thrombectomy
Sponsored by
About this trial
This is an interventional treatment trial for Hypothermia focused on measuring mechanical thrombectomy, selective brain cooling
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).
Sites / Locations
- Xuan Wu Hospital，Capital Medical University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
mechanical thrombectomy group
mechanical thrombectomy plus selective brain cooling group
Arm Description
Conventional mechanical thrombectomy
A microcatheter which was used to deploy the stent retriever was threaded into the femoral artery in the groin through a guiding catheter and up through the neck, until it reached beyond the clot causing the stroke under the assistance of micro-guide wire, 50 mL cold 0.9% saline (4°C) was infused into the ischemic territory at 10 mL/min through the microcatheter, thus allowing the cold solution to infuse into the ischemic territory prior to reperfusion. After that, mechanical thrombectomy with a stent retriever was performed to recanalize the occluded vessel as soon as possible. After the recanalization, cold 0.9% saline (4°C) was infused into the ischemic brain tissue through the guide catheter at 30 mL/min for 10 minutes.
Outcomes
Primary Outcome Measures
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
mRS 0-2
Secondary Outcome Measures
Dramatic early favorable response
an NIHSS of 0-2 or NIHSS improvement ≥ 8 points at 24 (-2/+12 hours) hours from randomization or before discharge if patient is discharged prior to the above time limit
Final infarct volume evaluated on CT/MR at 24 hours (-2/+12 hours)
Final infarct volume evaluated on CT/MR at 24 hours (-2/+12 hours)
The change of infarct volume compared with baseline.
The change of infarct volume compared with baseline.
Vessel recanalization
Vessel recanalization evaluated by angiography (one of CT angiography , MR Angiography and conventional angiography) at 24 hours (-2/+12 hours) in both treatment groups
Barthel Index at 90 days
Barthel Index at 90 days
NIHSS at 90 days
NIHSS at 90 days
Proportion of patients achieving excellent favorable outcomes defined as mRS 0-1 at 90 days
mRS 0-1 at 90 days
mRS shift analysis at 90 days
mRS shift analysis
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03163459
Brief Title
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
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Suspended
Why Stopped
Interim analysis
Study Start Date
February 6, 2018 (Actual)
Primary Completion Date
September 30, 2020 (Anticipated)
Study Completion Date
December 16, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Capital Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypothermia, Stroke, Acute
Keywords
mechanical thrombectomy, selective brain cooling
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
mechanical thrombectomy group
Arm Type
Active Comparator
Arm Description
Conventional mechanical thrombectomy
Arm Title
mechanical thrombectomy plus selective brain cooling group
Arm Type
Experimental
Arm Description
A microcatheter which was used to deploy the stent retriever was threaded into the femoral artery in the groin through a guiding catheter and up through the neck, until it reached beyond the clot causing the stroke under the assistance of micro-guide wire, 50 mL cold 0.9% saline (4°C) was infused into the ischemic territory at 10 mL/min through the microcatheter, thus allowing the cold solution to infuse into the ischemic territory prior to reperfusion. After that, mechanical thrombectomy with a stent retriever was performed to recanalize the occluded vessel as soon as possible. After the recanalization, cold 0.9% saline (4°C) was infused into the ischemic brain tissue through the guide catheter at 30 mL/min for 10 minutes.
Intervention Type
Drug
Intervention Name(s)
selective brain cooling by cold saline perfusion
Intervention Description
During the procedure, a microcatheter which was used to deploy the stent retriever was threaded into the femoral artery in the groin through a guiding catheter and up through the neck, until it reached beyond the clot causing the stroke under the assistance of micro-guide wire, 50 mL cold 0.9% saline (4°C) was infused into the ischemic territory at 10 mL/min through the microcatheter, thus allowing the cold solution to infuse into the ischemic territory prior to reperfusion. After that, mechanical thrombectomy with a stent retriever was performed to recanalize the occluded vessel as soon as possible. After the recanalization, cold 0.9% saline (4°C) was infused into the ischemic brain tissue through the guide catheter at 30 mL/min for 10 minutes.
Intervention Type
Device
Intervention Name(s)
mechanical thrombectomy
Intervention Description
conventional mechanical thrombectomy using Solitaire
Primary Outcome Measure Information:
Title
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
Description
mRS 0-2
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Dramatic early favorable response
Description
an NIHSS of 0-2 or NIHSS improvement ≥ 8 points at 24 (-2/+12 hours) hours from randomization or before discharge if patient is discharged prior to the above time limit
Time Frame
24 hours
Title
Final infarct volume evaluated on CT/MR at 24 hours (-2/+12 hours)
Description
Final infarct volume evaluated on CT/MR at 24 hours (-2/+12 hours)
Time Frame
24 hours
Title
The change of infarct volume compared with baseline.
Description
The change of infarct volume compared with baseline.
Time Frame
24 hours
Title
Vessel recanalization
Description
Vessel recanalization evaluated by angiography (one of CT angiography , MR Angiography and conventional angiography) at 24 hours (-2/+12 hours) in both treatment groups
Time Frame
24 hours
Title
Barthel Index at 90 days
Description
Barthel Index at 90 days
Time Frame
90 days
Title
NIHSS at 90 days
Description
NIHSS at 90 days
Time Frame
90 days
Title
Proportion of patients achieving excellent favorable outcomes defined as mRS 0-1 at 90 days
Description
mRS 0-1 at 90 days
Time Frame
90 days
Title
mRS shift analysis at 90 days
Description
mRS shift analysis
Time Frame
90 days
Other Pre-specified Outcome Measures:
Title
Mortality at 90 days
Description
Mortality
Time Frame
90 days
Title
Clinically significant ICH rates at 24 (-2/+12) hours.
Description
All intracerebral hemorrhages will be classified by a central core-lab using the Heidelberg criteria. Symptomatic ICH will be defined as per the SITS-MOST definition: deterioration in NIHSS score of ≥4 points within 24 hours from treatment and evidence of intraparenchymal hemorrhage type 2 in the 22 to 36 hours follow-up imaging scans. The incidence of any asymptomatic hemorrhage measured at 24 (-2/+12) hours will also be compared
Time Frame
24 hours
Title
Procedural related complications
Description
arterial perforation, arterial dissection, and embolization in a previously uninvolved vascular territory
Time Frame
From the operation to 24 hours after the operation
Title
Rectal temperature
Description
Rectal temperature
Time Frame
From 1 hour before operation to 1 hours after operation
Title
Hematocrit
Description
Hematocrit
Time Frame
From 3 hour before operation to 3 hours after operation
Title
blood biochemistry
Description
Routine blood test and blood biochemistry
Time Frame
From 3 hour before operation to 3 hours after operation
Title
Vital signs
Description
Vital signs
Time Frame
From 1 hour before operation to 24 hours after operation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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).
Facility Information:
Facility Name
Xuan Wu Hospital，Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100069
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
27197848
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.
Results Reference
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Short-duration Selective Brain Cooling for Patients Undergoing Mechanical Thrombectomy
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