A Phase IIIB, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Minor Neurologic Deficits (PRISMS)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 313
- 试验地点
- 88
- 主要终点
- Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 or 1 at Day 90
研究概览
简要总结
PRISMS is a double-blind, multicenter, randomized, Phase IIIb study to evaluate the efficacy and safety of intravenous (IV) alteplase in participants with mild acute ischemic strokes that do not appear to be clearly disabling. Participants will be randomized in a 1:1 ratio to receive within 3 hours of last known well time either 1) one dose of IV alteplase and one dose of oral aspirin placebo or 2) one dose of IV alteplase placebo and one dose of oral aspirin 325 milligrams (mg).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Mild ischemic stroke defined as the most recent pre-treatment NIHSS score of less than or equal to(</=) 5 and determined as not clearly disabling by the investigator
- •Study treatment initiated within 3 hours of last time participant seen normal
排除标准
- •Computed tomography (CT) or magnetic resonance imaging (MRI) findings of one of the following:
- •CT with clear large hypodensity that is greater than (>) one-third middle cerebral artery (MCA) territory (or >100 cubic centimeter [cc] if not in MCA territory)
- •MRI with clear large hyperintensity on concurrent diffusion-weighted (DW) and fluid-attenuated inversion recovery (FLAIR) that is greater than one-third MCA territory (or greater than 100 cc if not in MCA territory),
- •Imaging lesion consistent with acute hemorrhage, or
- •Evidence of intraparenchymal tumor
- •Disability prior to the presenting stroke
- •Standard contraindications to IV alteplase within 3 hours of symptom onset, including:
- •Head trauma, myocardial infarction, or previous stroke within the previous 3 months
- •Gastrointestinal or urinary tract hemorrhage within the previous 21 days
- •Major surgery within the previous 14 days
- •Arterial puncture at non-compressible site within the previous 7 days
- •Any history of ICH with the exception of those less than (<) 5 chronic microbleeds on MRI
- •Elevated blood pressure defined by systolic blood pressure >185 millimeters of mercury (mm Hg) or diastolic blood pressure >110 mm Hg, or treatments requiring aggressive measures to achieve acceptable levels
- •Treatment with unfractioned heparin within past 48 hours and activated partial thromboplastin time outside normal range
- •Blood glucose <50 milligrams per deciliter (mg/dL)
- •International normalized ratio >1.7
- •Platelet count <100,000 per cubic millimeter (/mm^3)
- •Treatment with a direct thrombin inhibitor (dabigatran) or a factor Xa inhibitor (apixaban, rivaroxaban, edoxaban) within the last 48 hours
- •Allergic reaction to study drug, aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs)
- •Females of childbearing age who are known to be pregnant and/or lactating
- •Inability to swallow, which would prevent oral intake of aspirin or aspirin placebo tablet
- •Other serious, advanced, or terminal illness that would confound the clinical outcome at 90 days
- •Current or recent (within 3 months) participation in another investigational drug treatment protocol
- •Anticipated inability to obtain 3-month follow-up assessments
- •Previous enrollment in PRISMS
- •Any other condition deemed by the investigator that would pose hazard to the participant with alteplase treatment
研究组 & 干预措施
Alteplase Placebo + Aspirin
Participants will receive single dose of IV alteplase placebo and aspirin orally.
干预措施: Alteplase Placebo (Drug)
Alteplase Placebo + Aspirin
Participants will receive single dose of IV alteplase placebo and aspirin orally.
干预措施: Aspirin (Drug)
Alteplase + Aspirin Placebo
Participants will receive single dose of IV alteplase and aspirin placebo orally.
干预措施: Alteplase (Drug)
Alteplase + Aspirin Placebo
Participants will receive single dose of IV alteplase and aspirin placebo orally.
干预措施: Aspirin Placebo (Drug)
结局指标
主要结局
Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 or 1 at Day 90
时间窗: Day 90
mRS score was determined by the investigator. The mRS is a 7 point scale (0-6) with 0: No symptoms at all, 1: No significant disability despite symptoms, able to carry out all usual duties and activities, 2: Slight disability, unable to carry out all previous activities but able to look after own affairs without assistance, 3: Moderate disability requiring some help, but able to walk without assistance, 4: Moderately severe disability, unable to walk without assistance and unable to attend to own bodily needs without assistance, 5: Severe disability, bedridden, incontinent and requiring constant nursing care and attention, 6: death prior to Day 90. Reported is the percentage of participants with scores of 0 or 1 on the mRS.
次要结局
- Percentage of Participants Who Died Due to Stroke and Neurological Disorders(From baseline to Day 90)
- Percentage of Participants With Serious Adverse Events(From baseline to Day 90)
- Distribution of Participants Across the Ordinal mRS(Day 90)
- Percentage of Participants With Symptomatic Intracranial Hemorrhage (ICH )(Within 36 hours after study drug administration on Day 1)
- Percentage of Participants With Any ICH(Within 36 hours after study drug administration on Day 1)
- Overall Mortality(From baseline to Day 90)
- Percentage of Participants With Adverse Events(From baseline up to Day 90: Non-serious adverse events were collected through the Day 30 visit. Serious adverse events were collected through the end of study at Day 90.)
- Percentage of Participants With Global Favorable Recovery on mRS, NIHSS, BI, and GOS(Day 90)