StrokePhase 2NCT04675762
Combinating Fingolimod With Alteplase Bridging With Thrombectomy in Acute Ischemic Stroke
A Phase 2 study testing Fingolimod in people with Stroke and Inflammation, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Stroke, Inflammation
- What is being tested?
- Fingolimod
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 118 participants
- Where
- 1 siteChina
- Study dates
- 15 Jan 2021to 15 Mar 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Imaging inclusion criteria: infarct core volume ≤ 100 mL and penumbra ≥ 15 mL with at least 20% mismatch (as evaluated by CTP).
- Patient, family member or legally responsible person depending on local ethics requirements has given informed consent.
Who cannot join
- Pre-existing neurologic disability (a score greater than 2 on the mRS).
- Contraindication of fingolimod.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The second affiliated hospital of Zhejiang University
Hangzhou, Zhejiang, 310009
Min Lou, PhD, MD, 13958007213, loumingxc@vip.sina.com
About this study
Official title: A Randomised Controlled Trial of Combinating an Immune Modulator Fingolimod With Alteplase Bridging With Mechanical Thrombectomy in Acute Ischemic Stroke
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.
Read the 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
- Being tested
- Fingolimod, Placebo
- Keywords
- Fingolimod Hydrochloride, Intravenous thrombolysis, Mechanical thrombectomy, Acute ischemic stroke
- Medical subject headings
- Stroke, Inflammation, Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FingolimodDrug
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.
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| fingolimod with standard therapy | Experimental | Patients will be treated with standard alteplase bridging and mechanical thrombectomy with fingolimod. Receives: Drug: Fingolimod |
| Placebo with standard therapy | Placebo comparator | Patients will be treated with standard alteplase bridging and mechanical thrombectomy with placebo. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%)
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
Measured: at 90 day
Secondary outcomes (9)
salvaged ischemic tissue index (%)
100*(baseline CTP ischemic lesion (mL) - 7 day DWI infarction lesion (mL))/ baseline CTP ischemic lesion (mL)
Measured: from baseline to 7 day
the growth in infarct volume (mL)
24 hour DWI infarct volume (mL) - 7 day DWI infarct volume (mL)
Measured: from 24 hour to 7 day
the penumbral salvage volume (mL)
(baseline CTP hypoperfusion volume (mL) - 24 hour DWI infarct volume (mL))
Measured: from baseline to 1 day
the frequency of parenchymal hemorrhage (PH) (%)
the presence of PH is defined according the standard from ECASS-2 study
Measured: at day 1
the change on the National Institute of Health stroke scale (NIHSS) score from baseline to 1 day
NIHSS: minimum value = 0, maximum value = 42, and higher scores mean severer symptoms
Measured: from baseline to 1 day
the change on the National Institute of Health stroke scale (NIHSS) score from baseline to 7 day
NIHSS: minimum value = 0, maximum value = 42, and higher scores mean severer symptoms
Measured: from baseline to 7 day
excellent recovery assessed by the ratio of modefied Rankin Scale (mRS) score of 0-1 (%)
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
Measured: at day 90
general recovery assessed by the ratio of modefied Rankin Scale (mRS) score of 0-3 (%)
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
Measured: at day 90
recovery assessed by modefied Rankin Scale (mRS) score
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
Measured: at day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2020
- Study start15 Jan 2021
- Primary completion15 Dec 2025 (estimated)
- Study completion15 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 118 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Shaoxing People's Hospital, Affiliated Hospital of Jiaxing University, Huizhou Municipal Central Hospital, The Second Affiliated Hospital of Jiaxing University, Jinhua Center Hospital, Taizhou Hospital
- Responsible party
- Sponsor
- Investigators
- Min Lou, PhD, MD, Study chair, Second Affiliated Hospital of Zhejiang University, School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04675762
- Sponsor's protocol ID
- IMMUTAS
- Status last verified
- Apr 2023
- First submitted
- 16 Dec 2020
- Last updated
- 18 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial of Combinating an Immune Modulator Fingolimod With Alteplase Bridging With Mechanical Thrombectomy in Acute Ischemic Stroke
- ClinicalTrials.gov ID
- NCT04675762
- Acronym / sponsor ID
- IMMUTAS
- Conditions
- Stroke, Inflammation
- Keywords
- Fingolimod Hydrochloride, Intravenous thrombolysis, Mechanical thrombectomy, Acute ischemic stroke
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 118 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Collaborators
- Shaoxing People's Hospital, Affiliated Hospital of Jiaxing University, Huizhou Municipal Central Hospital, The Second Affiliated Hospital of Jiaxing University, Jinhua Center Hospital, Taizhou Hospital
- Study start
- 15 Jan 2021 (actual)
- Primary completion
- 15 Dec 2025 (estimated)
- Study completion
- 15 Mar 2026 (estimated)
- First posted
- 19 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| fingolimod with standard therapy | Experimental | Drug: FingolimodPatients will be treated with standard alteplase bridging and mechanical thrombectomy with fingolimod. |
| Placebo with standard therapy | Placebo comparator | Other: PlaceboPatients will be treated with standard alteplase bridging and mechanical thrombectomy with placebo. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
- Imaging inclusion criteria: infarct core volume ≤ 100 mL and penumbra ≥ 15 mL with at least 20% mismatch (as evaluated by CTP).
- Patient, family member or legally responsible person depending on local ethics requirements has given informed consent.
Key exclusion criteria (2 listed)
- Pre-existing neurologic disability (a score greater than 2 on the mRS).
- Contraindication of fingolimod.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FingolimodPatients 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. | Drug | fingolimod with standard therapy |
| PlaceboPatients 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. | Other | Placebo with standard therapy |
Primary outcome
independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%)
Time frame: at 90 day
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
9 secondary outcomes
salvaged ischemic tissue index (%)
Time frame: from baseline to 7 day
the growth in infarct volume (mL)
Time frame: from 24 hour to 7 day
the penumbral salvage volume (mL)
Time frame: from baseline to 1 day
the frequency of parenchymal hemorrhage (PH) (%)
Time frame: at day 1
the change on the National Institute of Health stroke scale (NIHSS) score from baseline to 1 day
Time frame: from baseline to 1 day
the change on the National Institute of Health stroke scale (NIHSS) score from baseline to 7 day
Time frame: from baseline to 7 day
excellent recovery assessed by the ratio of modefied Rankin Scale (mRS) score of 0-1 (%)
Time frame: at day 90
general recovery assessed by the ratio of modefied Rankin Scale (mRS) score of 0-3 (%)
Time frame: at day 90
recovery assessed by modefied Rankin Scale (mRS) score
Time frame: at day 90
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Min Lou, PhD, MD study chair
Second Affiliated Hospital of Zhejiang University, School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fingolimod in people with Stroke and Inflammation, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Min Lou, PhD, MD (13958007213, loumingxc@vip.sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%) (time frame: at 90 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2023.