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Combinating Fingolimod With Alteplase Bridging With Mechanical Thrombectomy in Acute Ischemic Stroke (FAMTAIS)

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ClinicalTrials.gov Identifier: NCT02956200
Recruitment Status : Withdrawn
First Posted : November 6, 2016
Last Update Posted : March 31, 2020
Sponsor:
Information provided by (Responsible Party):
Second Affiliated Hospital, School of Medicine, Zhejiang University

Tracking Information
First Submitted Date  ICMJE October 11, 2016
First Posted Date  ICMJE November 6, 2016
Last Update Posted Date March 31, 2020
Actual Study Start Date  ICMJE November 2016
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 6, 2016)
salvaged ischemic tissue index (%) [ Time Frame: from baseline to 7 day ]
100*(baseline CTP ischemic lesion (mL) - 7 day DWI infarction lesion (mL))/ baseline CTP ischemic lesion (mL)
Original Primary Outcome Measures  ICMJE
 (submitted: November 2, 2016)
salvaged ischemic tissue index (%) [ Time Frame: from baseline to 7d ]
100*(baseline CTP ischemic lesion (mL) - 7d DWI infarction lesion (mL))/ baseline CTP ischemic lesion (mL)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2016)
  • the growth in infarct volume (mL) [ Time Frame: from 24 hour to 7 day ]
    24 hour DWI infarct volume (mL) - 7 day FLAIR infarct volume (mL)
  • the penumbral salvage volume (mL) [ Time Frame: from baseline to 1 day ]
    (baseline CTP hypoperfusion volume (mL) - 24 hour DWI infarct volume (mL))
  • the frequency of parenchymal hemorrhage (PH) (%) [ Time Frame: at day 1 ]
    the presence of PH is defined according the standard from ECASS-2 study
  • the change on the NIHSS score [ Time Frame: from baseline to 1 day ]
    baseline NIHSS score - 1 day NIHSS score
  • the change on the NIHSS score [ Time Frame: from baseline to 7 day ]
    baseline NIHSS score - 7 day NIHSS score
  • excellent recovery [ Time Frame: at day 90 ]
    modefied Rankin Scale (mRS) score of 0-1
  • independent recovery [ Time Frame: at day 90 ]
    mRS score of 0-2
Original Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2016)
  • the growth in infarct volume (mL) [ Time Frame: from 24h to 7d ]
    24h DWI infarct volume (mL) - 7d FLAIR infarct volume (mL)
  • the penumbral salvage volume (mL) [ Time Frame: from baseline to 1d ]
    (baseline CTP hypoperfusion volume (mL) - 24h DWI infarct volume (mL))
  • the frequency of parenchymal hemorrhage (PH) (%) [ Time Frame: at day 1 ]
    the presence of PH is defined according the standard from ECASS-2 study
  • the change on the NIHSS score [ Time Frame: from baseline to 1d ]
    baseline NIHSS score - 1d NIHSS score
  • the change on the NIHSS score [ Time Frame: from 1d to 7d ]
    baseline NIHSS score - 7d NIHSS score
  • excellent recovery [ Time Frame: at day 90 ]
    modefied Rankin Scale (mRS) score of 0-1
  • independent recovery [ Time Frame: at day 90 ]
    mRS score of 0-2
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combinating Fingolimod With Alteplase Bridging With Mechanical Thrombectomy in Acute Ischemic Stroke
Official Title  ICMJE A Randomised Controlled Trial of Combinating an Immune Modulator Fingolimod With Alteplase Bridging With Mechanical Thrombectomy in Acute Ischemic Stroke
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 6 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, open-label, blinded endpoint (PROBE) design clinical trial, in multiple stroke centers of China. The total sample size will be 98. Patients being treated with standard alteplase bridging and mechanical thrombectomy will be randomly assigned in a 1:1 ratio to receive oral fingolimod or standard care. The primary outcome will be the salvaged ischemic tissue from baseline to day 7. AIS patients with proximal cerebral arterial occlusions will have CT perfusion (CTP) before treatment, and multimodal MRI including diffusion and MR perfusion (MRP) at 24 hours and 7 days after receiving treatment. Clinical outcomes will be assessed using the National Institutes of Health Stroke Scale score (NIHSS) at baseline, day 1 and day 7 and the modified Rankin Scale (mRS) at 90 days. Circulating lymphocyte counts will be monitored with FACS at baseline, day 1 and day 7 to confirm the biological activity of fingolimod.

Patients aged between 18 and 85 with anterior circulation AIS who are eligible for alteplase and mechanical thrombectomy commenced within 6 hours of stroke onset will be enrolled if they present with an infarct core volume between 15-100 mL with at least 20% mismatch (as evaluated by CTP) and intracranial occlusion in proximal cerebral arteries. Exclusion criteria are (1) standard contraindications to alteplase or mechanical thrombectomy; (2) evidence of other diseases of the CNS; (3) pre-existing neurologic disability (a score greater than 2 on the mRS); (4) swallowing difficulties that would prevent administration of oral fingolimod; (5) patients with any history of bradyarrhythmia, atrioventricular block or current use of beta-blockers or verapamil; (6) concomitant use of antineoplastic, immunosuppressive or immune modulating therapies; (7) macular edema.

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 will also receive oral 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.

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 salvaged ischemic tissue((baseline ischemic lesion - 7d infarction lesion)/ baseline ischemic lesion) from baseline to day 7. Secondary outcomes are the growth in infarct volume between 24 hour DWI and day 7 FLAIR imaging, the penumbral salvage volume (baseline hypoperfusion volume - 24-hours infarct volume) between the baseline and day 1, the frequency of parenchymal hemorrhage (PH) at day 1 and the extent of clinical improvement at day 1 as measured by the change on the NIHSS score from baseline to day 1, the extent of clinical improvement from day 1 to day 7. The tertiary outcomes are the probability of excellent recovery at day 90 (mRS 0-1), independent recovery (mRS 0-2) and ordinal analysis of the modified Rankin scale.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Stroke
  • Inflammation
Intervention  ICMJE Drug: Fingolimod
Patients randomized to fingolimod will also receive oral 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.
Other Name: Fingolimod Hydrochloride
Study Arms  ICMJE
  • Experimental: fingolimod with standard therapy
    Patients will be treated with standard alteplase bridging and mechanical thrombectomy with fingolimod.
    Intervention: Drug: Fingolimod
  • No Intervention: standard therapy
    Patients will be treated with standard alteplase bridging and mechanical thrombectomy.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: March 27, 2020)
0
Original Estimated Enrollment  ICMJE
 (submitted: November 2, 2016)
96
Actual Study Completion Date  ICMJE December 2018
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients presenting with anterior circulation acute ischaemic stroke who are eligible for alteplase and mechanical thrombectomy commenced within 6 hours of stroke onset.
  2. Patient, family member or legally responsible person depending on local ethics requirements has given informed consent.
  3. Patient‟s age is 18-85 years.
  4. Arterial occlusion on CTA of the ICA, M1 or M2.
  5. Imaging inclusion criteria: infarct core volume between 15-100 mL with at least 20% mismatch (as evaluated by CTP).

Exclusion Criteria:

  1. Standard contraindications to alteplase or mechanical thrombectomy.
  2. Evidence of other diseases of the CNS.
  3. Pre-existing neurologic disability (a score greater than 2 on the mRS).
  4. Swallowing difficulties that would prevent administration of oral fingolimod.
  5. Patients with any history of bradyarrhythmia, atrioventricular block or current use of beta-blockers or verapamil.
  6. Patients with serious acute or chronic infection, or hepatic injury (over 3 times value of normal ALS or AST).
  7. Concomitant use of antineoplastic, immunosuppressive or immune modulating therapies.
  8. Macular edema.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02956200
Other Study ID Numbers  ICMJE YAN-2016-047
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Second Affiliated Hospital, School of Medicine, Zhejiang University
Study Sponsor  ICMJE Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Min Lou, MD,PhD Second Affiliated Hospital of Zhejiang University, School of Medicine
PRS Account Second Affiliated Hospital, School of Medicine, Zhejiang University
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP