A Pilot Randomized Controlled Trial of Conductive COOLing of the Ischemic PENumbra in Patients With Acute Ischemic Stroke.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 55
- 试验地点
- 5
- 主要终点
- Adherence to the intervention cooling system.
研究概览
简要总结
This study will develop and validate a novel, active/conductive combined head and neck cooling system to selectively cool the ischemic penumbra during the acute phase of stroke, reducing neuronal damage and improving stroke outcomes. It complements existing reperfusion therapies offering a scalable neuroprotective option which will have wider implications across diverse healthcare settings.
PHASE I: Technology Development & Test Bench Optimization (Years 1-2) PHASE II: Validation in healthy volunteers (Year 3)
PHASE III: Pilot, multicenter, randomized controlled (Phase 2a) trial (Year 4-5):
详细描述
PEN-Cool is a pilot, multicentre, randomized controlled trial evaluating a novel non-invasive active conductive combined head-and-neck cooling system for selective brain cooling in adults with acute ischemic stroke receiving reperfusion therapy. The study is part of a phased translational research programme involving technology development, validation in healthy volunteers, and clinical evaluation in patients with acute ischemic stroke.
The clinical trial will enroll 40 adult patients with acute ischemic stroke who are eligible for intravenous thrombolysis, endovascular thrombectomy, or both. Participants will be centrally randomized in a 1:1 ratio to either adjunctive selective brain cooling plus standard reperfusion therapy or standard reperfusion therapy alone.
In the intervention group, the conductive cooling system will be applied to the scalp and anterolateral and posterolateral neck. Cooling will begin before intravenous thrombolysis and/or endovascular thrombectomy in the emergency department or angiography suite and will continue for up to 120 minutes. The cooling interface will deliver temperatures ranging from -5°C to 0°C. Brain temperature will be monitored non-invasively using infrared tympanic membrane thermometry, while core body temperature will be monitored using a rectal or esophageal probe. Blood pressure, heart rate, and oxygen saturation will also be monitored.
Cooling will be discontinued if predefined safety or tolerability criteria are met, including intolerance, persistent cold-related shivering despite passive warming, core body temperature of 35°C or below, uncontrolled hypertension, symptomatic bradycardia or other unexpected medical events, or procedural complications.
The primary feasibility outcome is adherence to the cooling intervention, defined as receiving head cooling for at least 60% of the intended total cooling duration. Secondary feasibility outcomes include interruptions in cooling and monthly enrollment rate. Efficacy outcomes include early neurological improvement, defined as a 30% or greater improvement in NIHSS score at 24 hours, and good functional outcome, defined as a modified Rankin Scale score of 0-2 at 3 months. Safety outcomes include symptomatic bradyarrhythmia, uncontrolled hypertension, cold-related shivering, cervical or cerebral vasospasm requiring intra-arterial vasodilators, symptomatic intracranial hemorrhage, pneumonia, and mortality through 3 months. Process outcomes include time from hospital arrival to initiation of cooling and time from arrival to reperfusion therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label randomized controlled trial. Participants, care providers, investigators, and outcome assessors will not be masked to treatment allocation.
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adult participants of any gender aged 18 years or older and able to provide
- •informed consent.
- •1. Adult patients of any gender, presenting with acute ischemic stroke and eligible for reperfusion therapy IVT or EVT or Both as per guidelines.
排除标准
- •History of uncontrolled hypertension or cardiovascular disease.
- •Hematologic dyscrasias that can affect thrombosis like cryoglobulinemia or sickle cell disease or serum cold agglutinins.
- •Vasospastic disorders like Raynaud or thromboangiitis obliteran.
- •Skin lesions not allowing secure application of the cooling system
- •Surface Body temperature less than and equal to 35 degree Celcius at baseline
- •Blood pressure more than or equal to 185 by 110 mmHg not responsive to guideline-directed intravenous antihypertensive therapy
- •Known contraindications to hypothermia including hemodynamically unstable patients with new or symptomatic bradyarrhythmia known hematologic dyscrasias that affect thrombosis or vasospastic disorders such as Raynaud syndrome or thrombo angiitis obliterans.
- •Skin lesions on scalp or neck preventing secure application of the cooling cap.
- •Pre-morbid mRS more than or equal to 3
- •Patients with known diseases or conditions resulting in an expected life expectancy of less than or equal to 3 months
研究组 & 干预措施
Selective Brain Cooling + Standard Reperfusion Therapy
Participants will receive adjunctive non-invasive selective brain cooling using the novel active conductive combined head-and-neck cooling system in addition to standard reperfusion therapy (intravenous thrombolysis, endovascular thrombectomy, or both).
干预措施: PEN-Cool Conductive Head-and-Neck Cooling System (Device)
Standard Reperfusion Therapy / Routine Care
Participants will receive standard of care management for acute ischemic stroke according to institutional practice, including indicated intravenous thrombolysis and/or endovascular thrombectomy, without selective brain cooling.
干预措施: Standard Reperfusion Therapy / Routine Care (Other)
结局指标
主要结局
Adherence to the intervention cooling system.
时间窗: 3 months
Phase III (Feasibility outcomes) Primary feasibility outcome defined as the proportion of participants who will be adherent to the intervention. Adherence defined as undergoing head cooling for more than equal to 60 percent of the total time from the first application of the head and neck cooling system.
次要结局
- NIHSS(24 hours)
- Interruption of cooling system(3 months)
- mRS(3 months)
- Safety outcome(3 months)