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Short-duration Selective Brain Cooling for Patients Undergoing Mechanical Thrombectomy

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ClinicalTrials.gov Identifier: NCT03163459
Recruitment Status : Not yet recruiting
First Posted : May 23, 2017
Last Update Posted : June 2, 2017
Sponsor:
Information provided by (Responsible Party):
Ji Xunming, Capital Medical University

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.

Condition or disease Intervention/treatment Phase
Hypothermia Stroke, Acute Drug: selective brain cooling by cold saline perfusion Device: mechanical thrombectomy Phase 2 Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Short-duration Selective Brain Cooling for Ischemic Stroke Patients Undergoing Mechanical Thrombectomy: a Randomized Controlled Trial
Estimated Study Start Date : June 1, 2017
Estimated Primary Completion Date : May 31, 2018
Estimated Study Completion Date : September 16, 2018

Arm Intervention/treatment
Active Comparator: mechanical thrombectomy group
Conventional mechanical thrombectomy
Device: mechanical thrombectomy
conventional mechanical thrombectomy using Solitaire

Experimental: mechanical thrombectomy plus selective brain cooling group
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.
Drug: selective brain cooling by cold saline perfusion
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.

Device: mechanical thrombectomy
conventional mechanical thrombectomy using Solitaire




Primary Outcome Measures :
  1. 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 [ Time Frame: 90 days ]
    mRS 0-2


Secondary Outcome Measures :
  1. Dramatic early favorable response [ Time Frame: 24 hours ]
    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

  2. Final infarct volume evaluated on CT/MR at 24 hours (-2/+12 hours) [ Time Frame: 24 hours ]
    Final infarct volume evaluated on CT/MR at 24 hours (-2/+12 hours)

  3. The change of infarct volume compared with baseline. [ Time Frame: 24 hours ]
    The change of infarct volume compared with baseline.

  4. Vessel recanalization [ Time Frame: 24 hours ]
    Vessel recanalization evaluated by angiography (one of CT angiography , MR Angiography and conventional angiography) at 24 hours (-2/+12 hours) in both treatment groups

  5. Barthel Index at 90 days [ Time Frame: 90 days ]
    Barthel Index at 90 days

  6. NIHSS at 90 days [ Time Frame: 90 days ]
    NIHSS at 90 days

  7. Proportion of patients achieving excellent favorable outcomes defined as mRS 0-1 at 90 days [ Time Frame: 90 days ]
    mRS 0-1 at 90 days

  8. mRS shift analysis at 90 days [ Time Frame: 90 days ]
    mRS shift analysis


Other Outcome Measures:
  1. Mortality at 90 days [ Time Frame: 90 days ]
    Mortality

  2. Clinically significant ICH rates at 24 (-2/+12) hours. [ Time Frame: 24 hours ]
    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

  3. Procedural related complications [ Time Frame: From the operation to 24 hours after the operation ]
    arterial perforation, arterial dissection, and embolization in a previously uninvolved vascular territory

  4. Rectal temperature [ Time Frame: From 1 hour before operation to 1 hours after operation ]
    Rectal temperature

  5. Hematocrit [ Time Frame: From 3 hour before operation to 3 hours after operation ]
    Hematocrit

  6. blood biochemistry [ Time Frame: From 3 hour before operation to 3 hours after operation ]
    Routine blood test and blood biochemistry

  7. Vital signs [ Time Frame: From 1 hour before operation to 24 hours after operation ]
    Vital signs



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03163459


Contacts
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Contact: Chuanjie Wu, MD 18911366882 wuchuanjie8557@163.com
Contact: Xunming Ji, MD 13911077166 jixunming@vip.163.com

Sponsors and Collaborators
Capital Medical University

Publications:
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Responsible Party: Ji Xunming, Vice President, Capital Medical University
ClinicalTrials.gov Identifier: NCT03163459     History of Changes
Other Study ID Numbers: ET-EH
First Posted: May 23, 2017    Key Record Dates
Last Update Posted: June 2, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Keywords provided by Ji Xunming, Capital Medical University:
mechanical thrombectomy
selective brain cooling

Additional relevant MeSH terms:
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Stroke
Hypothermia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Body Temperature Changes
Signs and Symptoms