Fingolimod as a Treatment of Cerebral Edema After Intracerebral Hemorrhage
NCT ID: NCT04088630
Last Updated: 2025-01-23
Study Results
Results available
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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Recruitment Status
COMPLETED
Clinical Phase
EARLY_PHASE1
Total Enrollment
28 participants
Study Classification
INTERVENTIONAL
Study Start Date
2020-08-07
Study Completion Date
2024-06-05
Brief Summary
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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).
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Detailed Description
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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.
Conditions
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Intracerebral Hemorrhage
Cerebral Edema
Stroke Hemorrhagic
Intracerebral Hemorrhage, Hypertensive
Intracerebral Hemorrhage Intraparenchymal
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Randomized, double-blinded, placebo-controlled pilot trial.
Primary Study Purpose
TREATMENT
Blinding Strategy
TRIPLE
Participants
Investigators
Outcome Assessors
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.
Study Groups
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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.
Group Type
EXPERIMENTAL
Fingolimod
Intervention Type
DRUG
A single dose of 0.5 mg oral fingolimod within 24 hours of symptom onset
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
Group Type
PLACEBO_COMPARATOR
Placebo
Intervention Type
DRUG
A single oral placebo pill within 24 hours of symptom onset
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.
Group Type
EXPERIMENTAL
Open-label Fingolimod
Intervention Type
DRUG
A single dose of 0.5 mg fingolimod through an NGT or Dobhoff tube within 24 hours of symptom onset
Interventions
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Fingolimod
A single dose of 0.5 mg oral fingolimod within 24 hours of symptom onset
Intervention Type
DRUG
Placebo
A single oral placebo pill within 24 hours of symptom onset
Intervention Type
DRUG
Open-label Fingolimod
A single dose of 0.5 mg fingolimod through an NGT or Dobhoff tube within 24 hours of symptom onset
Intervention Type
DRUG
Eligibility Criteria
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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.
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.
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.
Minimum Eligible Age
18 Years
Maximum Eligible Age
80 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Wake Forest University Health Sciences
OTHER
Sponsor Role
lead
National Center for Advancing Translational Sciences (NCATS)
NIH
Sponsor Role
collaborator
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Stacey Q Wolfe, MD
Role: PRINCIPAL_INVESTIGATOR
Wake Forest University Health Sciences
Locations
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Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Site Status
Countries
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United States
References
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Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Related Links
Access external resources that provide additional context or updates about the study.
https://ClinicalTrials.gov/show/NCT01827046
Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III
https://ClinicalTrials.gov/show/NCT03342664
MIND: Artemis in the Removal of Intracerebral Hemorrhage
https://ClinicalTrials.gov/show/NCT02880878
ENRICH: Early MiNimally-invasive Removal of IntraCerebral Hemorrhage (ICH)
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
IRB00060619
Identifier Type: -
Identifier Source: org_study_id
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