Short-duration Selective Brain Cooling for Patients Undergoing Mechanical Thrombectomy

Not yet recruiting

Phase 2/3 Results N/A

Trial Description

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.

Conditions

Interventions

  • Mechanical Thrombectomy (Merci Retriever)Device
    Other Names: Penumbra system; TREVO; Solitaire
    Intervention Desc: conventional mechanical thrombectomy using Solitaire
    ARM 1: Kind: Experimental
    Label: mechanical thrombectomy group
    Description: Conventional mechanical thrombectomy
    ARM 2: Kind: Experimental
    Label: mechanical thrombectomy plus selective brain cooling group
    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.
  • Selective brain cooling by cold saline perfusion Drug
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: mechanical thrombectomy plus selective brain cooling group
    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.

Outcomes

Type Measure Time Frame Safety Issue
Primary 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 90 days
Secondary Dramatic early favorable response 24 hours
Secondary Final infarct volume evaluated on CT/MR at 24 hours (-2/+12 hours) 24 hours
Secondary The change of infarct volume compared with baseline. 24 hours
Secondary Vessel recanalization 24 hours
Secondary Barthel Index at 90 days 90 days
Secondary NIHSS at 90 days 90 days
Secondary Proportion of patients achieving excellent favorable outcomes defined as mRS 0-1 at 90 days 90 days
Secondary mRS shift analysis at 90 days 90 days

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