Fingolimod as a Treatment of Cerebral Edema After Intracerebral Hemorrhage

Early Phase 1CompletedNCT04088630

Wake Forest University Health Sciences28 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Intracerebral Hemorrhage Cerebral Edema Stroke Hemorrhagic Intracerebral Hemorrhage, Hypertensive Intracerebral Hemorrhage Intraparenchymal

Interventions

FingolimodDRUG

A single dose of 0.5 mg oral fingolimod within 24 hours of symptom onset

PlaceboDRUG

A single oral placebo pill within 24 hours of symptom onset

Open-label FingolimodDRUG

A single dose of 0.5 mg fingolimod through an NGT or Dobhoff tube within 24 hours of symptom onset

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Outcomes

Primary Outcomes

Number of Participants With Clinically Significant Cardiac Events

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.

Time frame: up to 30 days post-ictus

Rate of Nosocomial Infections (UTI, Sepsis, and Pneumonia)

Rate of nosocomial infections (UTI, sepsis, and pneumonia) by group

Time frame: up to 90 days post-ictus

Rate of Neurologic Decline

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.

Time frame: up to 30 days post-ictus

Secondary Outcomes

Rate of Successful Administration of Fingolimod Through an NGT or Dobhoff Tube

Rate of successful administration of fingolimod through an NGT or Dobhoff tube in Open-label group only

Time frame: Enrollment

Percent Change in Lymphocyte Subpopulations of CD4+ T Cells

Time frame: Enrollment to 30 days

Percent Change in Lymphocyte Subpopulations of CD8+ T Cells

Percent change in lymphocyte subpopulations of CD8+ T Cells

Time frame: Enrollment and 30 days

Data from ClinicalTrials.gov

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