Combinating Fingolimod With Alteplase Bridging With Thrombectomy in Acute Ischemic Stroke

NCT ID: NCT04675762

Last Updated: 2023-04-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-15
• Study Completion Date: 2026-03-15

Brief Summary

Proof-of concept clinical trials have indicated that the sphingosine-1-phosphate receptor modulator fingolimod may be efficacious in attenuating brain inflammation and improving clinical outcomes in patients with AIS as a single therapy beyond 4.5 hours of disease onset, or in combination with alteplase within 4.5 hours of disease onset. So in this study the investigators try to determine whether the addition of fingolimod, administered within 24 hours after the onset of symptoms in patients receiving alteplase bridging with mechanical thrombectomy, improves radiologic and clinical outcomes.

Detailed Description

This is a prospective, randomized, double-blind, placebo-controlled design clinical trial, in multiple stroke centers of China. The total sample size will be 118. Patients being treated with standard alteplase bridging and mechanical thrombectomy will be randomly assigned in a 1:1 ratio to receive fingolimod or placebo.

Patients aged between 18 and 85 with anterior circulation AIS who are eligible for alteplase and mechanical thrombectomy commenced within 24 hours of stroke onset or awakening with stroke (if within 24 hours from the midpoint of sleep) will be enrolled if they present with an infarct core volume ≤ 100 mL and penumbra ≥ 15 mL with at least 20% mismatch (as evaluated by CTP) and intracranial occlusion in proximal cerebral arteries. Exclusion criteria are (1) pre-existing neurologic disability (a score greater than 2 on the mRS); (2) contraindication of fingolimod.

As standard care, all patients will receive standard dose intravenous alteplase (0.9 mg per kilogram, the first 10% administered as an initial bolus and the remainder over a 1-hour period, with a maximum dose of 90 mg) and mechanical thrombectomy delivered at the site of intracranial vessel occlusion. Patients randomized to fingolimod group or placebo group will receive fingolimod (Gilenya, Novartis) at a dosage of 0.5 mg or placebo once daily, for three consecutive days, with the first dose being given at the time in which patients are enrolled which is about one hour prior to mechanical thrombectomy.

The kinetics of lymphocyte subset alteration will be monitored in whole-blood samples from all fingolimod- treated patients at the baseline, which will precede the first dose, day 1 and day 7. Mononuclear cells will be isolated from the whole-blood specimens and stained with antibodies to CD4-FITC, CD8-PE, CD19-PerCP, CD56-PE (BD Biosciences, Franklin Lakes, NJ, USA). Data will be acquired using a FACS Caliber (Becton Dickinson Immunocytometry Systems, San Jose, CA, USA) and analyzed with Flow Jo software (Tree Star, Ashland, OR, USA).

The primary outcome is the ratio of mRS 0-2 (%) at 90 day. Secondary outcomes are the salvaged ischemic tissue index (%) from baseline to 7 day, the growth in infarct volume (mL) from 24 hour to 7 day, the penumbral salvage volume (mL) from baseline to 1 day, the frequency of parenchymal hemorrhage (PH) (%) at day 1, the change on the NIHSS score from baseline to 1 day, the change on the NIHSS score from baseline to 7 day, mRS 0-1 (%) at 90 day, and mRS at 90 day.

Conditions

Stroke; Inflammation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

fingolimod with standard therapy

Patients will be treated with standard alteplase bridging and mechanical thrombectomy with fingolimod.

Group Type: EXPERIMENTAL

Fingolimod

Intervention Type: DRUG

Patients randomized to fingolimod will also receive fingolimod (Gilenya, Novartis) at a dosage of 0.5 mg once daily, for three consecutive days, with the first dose being given at the time in which patients are enrolled which is about one hour prior to mechanical thrombectomy.

Placebo with standard therapy

Patients will be treated with standard alteplase bridging and mechanical thrombectomy with placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Patients randomized to fingolimod will also receive placebo once daily, for three consecutive days, with the first dose being given at the time in which patients are enrolled which is about one hour prior to mechanical thrombectomy.

Interventions

Fingolimod

Patients randomized to fingolimod will also receive fingolimod (Gilenya, Novartis) at a dosage of 0.5 mg once daily, for three consecutive days, with the first dose being given at the time in which patients are enrolled which is about one hour prior to mechanical thrombectomy.

Intervention Type: DRUG

Placebo

Patients randomized to fingolimod will also receive placebo once daily, for three consecutive days, with the first dose being given at the time in which patients are enrolled which is about one hour prior to mechanical thrombectomy.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients presenting with anterior circulation acute ischaemic stroke who are eligible for alteplase and mechanical thrombectomy commenced within 24 hours of stroke onset or awakening with stroke (if within 24 hours from the midpoint of sleep).
• Patient's age is 18-85 years.
• Arterial occlusion on CTA of the ICA, M1 or M2.
• Patient, family member or legally responsible person depending on local ethics requirements has given informed consent.

Exclusion Criteria

• Pre-existing neurologic disability (a score greater than 2 on the mRS).
• Contraindication of fingolimod.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shaoxing People's Hospital

OTHER

Sponsor Role: collaborator

Affiliated Hospital of Jiaxing University

OTHER

Sponsor Role: collaborator

Huizhou Municipal Central Hospital

OTHER

Sponsor Role: collaborator

The Second Affiliated Hospital of Jiaxing University

OTHER

Sponsor Role: collaborator

Jinhua Center Hospital

UNKNOWN

Sponsor Role: collaborator

Taizhou Hospital

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Min Lou, PhD, MD

Role: STUDY_CHAIR

Second Affiliated Hospital of Zhejiang University, School of Medicine

Locations

The second affiliated hospital of Zhejiang University

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Min Lou, PhD, MD

Role: CONTACT

loumingxc@vip.sina.com

13958007213

Facility Contacts

Min Lou, PhD, MD

Role: primary

loumingxc@vip.sina.com

13958007213

Other Identifiers

IMMUTAS

Identifier Type: -

Identifier Source: org_study_id