Clinical trial NCT04088630: Fingolimod as a Treatment of Cerebral Edema After Intracerebral Hemorrhage
Official title: Fingolimod as a Treatment of Cerebral Edema After Intracerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Intracerebral Hemorrhage
Cerebral Edema
Stroke Hemorrhagic
Intracerebral Hemorrhage, Hypertensive
Intracerebral Hemorrhage Intraparenchymal
Keywords: Fingolimod
Neurologic Deficits
Brain Injury
Stroke
Intracerebral hemorrhage
Neuroimmunomodulation
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2019-09-13
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blinded, placebo-controlled pilot trial.
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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.

Exclusion Criteria:

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 ≤ 4.

Platelet count \< 100,000; INR \> 1.4. 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.

Primary outcomes:
measure: Number of Participants With Clinically Significant Cardiac Events
timeFrame: up to 30 days post-ictus
measure: Rate of Nosocomial Infections (UTI, Sepsis, and Pneumonia)
timeFrame: up to 90 days post-ictus
measure: Rate of Neurologic Decline
timeFrame: up to 30 days post-ictus
Secondary outcomes:
measure: Rate of Successful Administration of Fingolimod Through an NGT or Dobhoff Tube
timeFrame: Enrollment
measure: Percent Change in Lymphocyte Subpopulations of CD4+ T Cells
timeFrame: Enrollment to 30 days
measure: Percent Change in Lymphocyte Subpopulations of CD8+ T Cells
timeFrame: Enrollment and 30 days
measure: Percent Change in Lymphocyte Subpopulations of CD19+ B Cells
timeFrame: Enrollment and 30 days
measure: Change in Hematoma Volume Obtained by MRI
timeFrame: Enrollment and 365 days
measure: Change in Hematoma Volume Obtained by CT
timeFrame: Enrollment and 365 days
measure: Change in Peri-hematomal Edema Volume Obtained by CT
timeFrame: Enrollment to 365 days
measure: Change in Peri-hematomal Edema Volume Obtained by MRI
timeFrame: Enrollment to 365 days
measure: National Institutes of Health Stroke Scale Total Score (NIHSS)
timeFrame: 365 days
measure: Interviewer-administered Modified Rankin Scale (mRS)
timeFrame: 365 days post-ictus
measure: Patient-Reported Outcomes Measurement Information (PROMIS) 10 Questionnaire
timeFrame: 365 days
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: 365 days
measure: Western Aphasia Battery-Revised (WAB-R)
timeFrame: 365 days
measure: Mortality
timeFrame: 30 days
measure: Mortality
timeFrame: 90 days
measure: All Cause Mortality
timeFrame: up to 365 days
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Stacey Q Wolfe, MD
role: PRINCIPAL_INVESTIGATOR
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