Fingolimod as a Treatment of Cerebral Edema After Intracerebral Hemorrhage
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Number of Participants With Clinically Significant Cardiac Events
研究概览
简要总结
The purpose of this study is to test the safety and effectiveness of a single dose of fingolimod in patients with primary spontaneous intracerebral hemorrhage (ICH).
详细描述
This is a double-blinded, placebo-controlled pilot trial of fingolimod in patients with primary spontaneous intracerebral hemorrhage. Eligible participants will be allocated to study groups using fixed allocation randomization and a computer-based random number-generating allocation. For those patients who meet all inclusion criteria without exclusion criteria subjects will receive oral or nasogastric tube (NGT) or Dobhoff feeding tube administration of fingolimod versus placebo. Participants will be monitored at time of enrollment and days 1, 3 5, 7, and 14 (discharge dependent) by 2 blinded assessors (neuroscience subspecialists) and will receive standard of care for the duration of the study. After discharge from the hospital, participants will enter a follow up phase of 12 months, with clinic visits at 30±14 days, 90±14 days, 180±14 days, and 365±14 days. They will receive a standard of care neuroimaging at these follow up time-points and will be assessed with the pre-selected outcome assessments established by the NINDS Common Data Elements for Stroke.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Consented participants who can be administered an oral drug will be allocated to Fingolimod or Placebo study groups using a computer-based random number-generating allocation. Consented participants who are unable to be administered the oral drug or placebo are assigned to the open-label group. The study pharmacist will be the only member of the study to be unblinded to oral fingolimod or placebo randomization.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has given written informed consent to participate in the study in accordance with required regulations; if a participant is not capable of providing informed consent, written consent must be obtained from the participant's legally authorized representative (LAR). When the LAR is not available for consent, Docusign for econsent may be obtained.
- •Stated willingness to comply with all study procedures and availability for the duration of the study.
- •Men and non-pregnant women ages 18-80 years old Has a confirmed diagnosis of spontaneous supratentorial ICH. The presence of cerebellar ICH is exclusionary. Presence of hydrocephalus due to mass effect and cerebral edema is not exclusionary. If the patient has hydrocephalus requiring CSF drainage, an external ventricular drain will be placed as standard of care and will not be exclusionary.
- •Symptoms less than 24 hours prior to enrollment if all eligibility criteria are met. An unknown time of onset is exclusionary. Use the time the patient was last known to be well for patients that awaken from sleep with symptoms.
- •Has a GCS score ≥ 5 on presentation. Has a National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 on presentation.
- •Maintenance of SBP < 200 mmHg at the time of enrollment and randomization. Historical Modified Rankin Scale score of 0-2.
排除标准
- •Men or women < 18 years old Incarcerated patients ICH known as a result of trauma. Primary intraventricular hemorrhage without significant intraparenchymal component.
- •Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly, Moyamoya disease, hemorrhagic conversion of an ischemic infarct, recurrence of recent (< 1 year) hemorrhage, neoplasms diagnosed with radiographic imaging.
- •Patients with unstable mass or evolving intracranial compartment syndrome. Brainstem hemorrhage or irreversible impaired brain stem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS ≤
- •Platelet count < 100,000; INR > 1.
- •Any irreversible coagulopathy or known clotting disorder. Known history of Mobitz Type II second-degree or third-degree atrioventricular (AV) block or sick sinus syndrome.
- •Admission within the past 6 months for the following: myocardial infarction, unstable angina, stroke, decompensated heart failure requiring hospitalization, or Class III/IV heart failure.
- •Baseline QTc interval ≥500 ms. Current treatment with Class Ia or Class III anti-arrhythmic drugs. Implanted cardiac devices that are not compatible with the desired MRI sequences needed for the study (non-contrast T1, T2, SWI/GRE, and FLAIR sequences).
- •Abnormal liver function or liver failure. Active acute infection that is deemed by the Principal Investigator to be clinically significant.
- •Chronic viral or fungal infection. Active use of antineoplastic, immunosuppressive, or immunomodulating therapies. Leukopenia with a WBC < 2.0 x 109/L. Not expected to survive to the 365 day visit due to co-morbidities or is DNR/DNI status prior to randomization.
- •Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
- •Concomitant enrollment in another interventional study. Inability or unwillingness of participant or legal guardian/representative to give written informed consent.
研究组 & 干预措施
Fingolimod
In addition to Standard of care treatment, those participants randomized to the fingolimod group will receive a single dose of 0.5 mg oral fingolimod within 24 hours of symptom onset.
干预措施: Fingolimod (Drug)
Placebo Control
In addition to Standard of care treatment, those participants randomized to the control group will receive a single dose placebo pill within 24 hours of symptom onset
干预措施: Placebo (Drug)
Open-label Fingolimod
In addition to standard of care treatment,10 subjects who are unable to be administered oral medication will be assigned to the open-label group who will receive a single dose of 0.5 mg oral fingolimod within 24 hours of symptom onset to assess feasibility of administration through NGT or Dobhoff tube.
干预措施: Open-label Fingolimod (Drug)
结局指标
主要结局
Number of Participants With Clinically Significant Cardiac Events
时间窗: up to 30 days post-ictus
Number of participants with clinically significant cardiac events. Clinically significant cardiac events include myocardial infarction, unstable angina, stroke, transient ischemic attack, any heart failure, bradycardia and heart block. Cardiac events were monitored with telemetry up to and after 72 hours while hospitalized. A check in was performed at 30 days with an in-person clinical or hospital visit to ascertain any cardiac events via patient discussion and medical record review.
Rate of Nosocomial Infections (UTI, Sepsis, and Pneumonia)
时间窗: up to 90 days post-ictus
Rate of nosocomial infections (UTI, sepsis, and pneumonia) by group
Rate of Neurologic Decline
时间窗: up to 30 days post-ictus
considered a change ≥ 4 points of the NIHSS between enrollment and 30 days post-ictus. A higher score indicates higher severity and poorer prognosis. Scale is 0-42.
次要结局
- Mortality(90 days)
- All Cause Mortality(up to 365 days)
- Rate of Successful Administration of Fingolimod Through an NGT or Dobhoff Tube(Enrollment)
- Percent Change in Lymphocyte Subpopulations of CD4+ T Cells(Enrollment to 30 days)
- Percent Change in Lymphocyte Subpopulations of CD8+ T Cells(Enrollment and 30 days)
- Percent Change in Lymphocyte Subpopulations of CD19+ B Cells(Enrollment and 30 days)
- Change in Hematoma Volume Obtained by MRI(Enrollment and 365 days)
- Change in Hematoma Volume Obtained by CT(Enrollment and 365 days)
- Change in Peri-hematomal Edema Volume Obtained by CT(Enrollment to 365 days)
- Change in Peri-hematomal Edema Volume Obtained by MRI(Enrollment to 365 days)
- National Institutes of Health Stroke Scale Total Score (NIHSS)(365 days)
- Interviewer-administered Modified Rankin Scale (mRS)(365 days post-ictus)
- Patient-Reported Outcomes Measurement Information (PROMIS) 10 Questionnaire(365 days)
- Montreal Cognitive Assessment (MoCA)(365 days)
- Western Aphasia Battery-Revised (WAB-R)(365 days)