Phase 2/3 Study of Intravenous Thrombolysis and Hypothermia for Acute Treatment of Ischemic Stroke
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 120
- 试验地点
- 31
- 主要终点
- Incidence of Any Intracranial Hemorrhage (ICH) Within 48 Hours of Stroke Onset
研究概览
简要总结
The purpose of this trial is to determine whether the combination of thrombolysis and hypothermia is superior to thrombolysis alone for the treatment of acute ischemic stroke.
详细描述
A stroke is usually caused by a blockage in one of the arteries that carries blood to the brain. Research has shown that tissue plasminogen activator (tPA)-a naturally occurring protein that opens blocked arteries by dissolving blood clots - activates the body's ability to dissolve recently formed blood clots and reduces or prevents the brain damage caused by a stroke.
The Food and Drug Administration (FDA) has approved the use of tPA for people having a stroke when taken within 3 hours of stroke onset.
Researchers believe that a lower body temperature (hypothermia) may be beneficial while a stroke is happening because hypothermia may prevent further brain injury, or may make the stroke less damaging.
Patients will receive a standard stroke evaluation, which includes blood tests, a computed tomography (CT) scan, complete physical and neurological examinations, and an electrocardiogram (EKG) to determine eligibility for the study.
There are two study groups - tPA alone or tPA with cooling (hypothermia). Participants will be randomly assigned to one of the two study groups. Length of participation (including observation after the patient leaves the hospital) is 90 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 22 Years 至 82 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 22 to 82 years old inclusive
- •Patient receiving IV rt-PA using standard guidelines
- •NIHSS score ≥ 7 and ≤ 20 (right hemisphere) or ≥ 7 and ≤ 24 (left hemisphere) at the time of randomization
- •Pre-stroke mRS 0-1
- •Able to begin endovascular phase of hypothermia within 2 hours of tPA completion
- •Written Informed Consent, signed and dated by the patient (or patient's authorized representative)
排除标准
- •Etiology other than ischemic stroke
- •Item 1a on NIHSS > 1 at the time of randomization
- •Clinical symptoms consistent with brainstem or cerebellar stroke
- •Classic lacunar syndrome with imaging confirmation of small deep ischemia, but randomization will not be delayed for neuroimaging other than initial scan to exclude hemorrhage
- •Known contraindications to hypothermia, such as known hematologic dyscrasias that affect thrombosis (cryoglobulinemia, Sickle cell disease, serum cold agglutinins), or vasospastic disorders such as Raynaud's or thromboangiitis obliterans
- •Known co-morbid conditions that are likely to complicate therapy in the opinion of the investigator, e.g., i. Heart failure (NYHA class III and IV)* ii. Uncompensated arrhythmia iii. Severe Liver disease iv. History of pelvic or abdominal mass likely to compress inferior vena cava v. IVC filters vi. HIV positive vii. Clinically active hypo or hyperthyroidism viii. Renal insufficiency likely to impair meperidine clearance ix. Chronic ethanol abuse x. History of HIT (heparin induced thrombocytopenia)
- •Pregnancy (All women of child-bearing potential must have a negative pregnancy test, urine or blood, prior to therapy.)
- •Medical conditions likely to interfere with patient assessment.
- •Known allergy to meperidine or buspirone
- •Currently taking or used within previous 14 days MAO-I class of medication.
- •Life expectancy < 6 months
- •Not likely to be available for long-term follow-up
- •Use, or planned use, of intra-arterial thrombolysis, mechanical clot removal, or other experimental or approved acute therapy for this stroke event
- •Chest radiograph or clinical presentation suggestive of pneumonia or clinically significant pulmonary edema at baseline.
- •Temperature upon admission greater than or equal to 38°C
研究组 & 干预措施
Group 2 : IV t-PA and hypothermia and anti-shivering treatment
IV tpa and hypothermia and anti-shivering treatment
干预措施: hypothermia and anti-shivering treatment (Device)
结局指标
主要结局
Incidence of Any Intracranial Hemorrhage (ICH) Within 48 Hours of Stroke Onset
时间窗: 48 hours
Incidence (number) of any intracranial hemorrhage (ICH) (whether or not symptomatic) within 48 hours of stroke onset will be presented by treatment group and overall.
90 Day Mortality
时间窗: 90 days
Mortality prior to the 90-day evaluation.
The Primary Outcome is the Proportion of Patients Achieving a Favorable Outcome Defined as Modified Rankin Scale Score of 0 or 1, Assessed 90 Days After Treatment.
时间窗: 90 days
Modified Rankin describes disability: 0 is free of any disability or symptoms, 6 is death, and higher grades between 0 and 6 reflect progressively greater disability
Incidence of Any Symptomatic Intracranial Hemorrhage (sICH) Within 48 Hours of Stroke Onset
时间窗: 48 hours
Incidence (number) of Symptomatic ICH (sICH) within 48 hours of stroke onset will be presented by treatment group and overall. Patients with neuroworsening (4 or more point increase in NIHSS , or a decline in the NIHSS consciousness item 1A score of more than 1 point, or a motor deterioration lasting more than 8 hours, all not due to iatrogenic cause) and hemorrhage seen on brain images in whom the investigator attributes the clinical change to the hemorrhage.
Incidence of Pneumonia
时间窗: 7 days or discharge whichever comes first
Number subjects diagnosed with pneumonia according to CDC criteria will be presented by treatment group and overall, regardless of seriousness
次要结局
- NIHSS Scores at 90 Days(90 days)
- The Barthel Index Measure of Activities of Daily Living;(90 days)
研究者
Patrick Lyden
Principal Investigator
Cedars-Sinai Medical Center