Cilostazol Dexborneol Versus Placebo for Microcirculation Dysfunction After Reperfusion Therapy in Patients With Acute Ischemic Stroke With Large Vessel Occlusion (CRYSTAL)

September 27, 2023 updated by: yilong Wang, Beijing Tiantan Hospital

Cilostazol Dexborneol Versus Placebo for Microcirculation Dysfunction After Reperfusion Therapy in Patients With Acute Ischemic Stroke With Large Vessel Occlusion: A Phase Ⅱa,Prospective,Multicenter,Randomized, Double-blind,Placebo-controlled Parallel Trial

This study aims to evaluate the efficacy of Y-6 sublingual tablets in improving microcirculation dysfunction and reducing thrombo-inflammation in patients who had AIS caused by LVO and received reperfusion therapy. Moreover, we expect to evaluate the safety of using Y-6 sublingual tablet in such study population.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study rationale is based on the following scheme: in patients with acute ischemic stroke caused by LVO, receiving reperfusion therapy may cause futile recanalization and thus lead to microcirculation dysfunction and thrombo-inflammation as consequences. Cilostazol has antiplatelet effects and BBB protection and Dexborneol has anti-inflammatory effects; therefore, the multi-component tablet may exert neuroprotective effects in terms of improving microcirculation dysfunction and reducing thrombo-inflammation in patients with AIS after reperfusion therapy.

The primary purpose of this study is to investigate the proportion of modified-Rankin scale (mRS) score recovered to 0~1 score at 90±7 days after randomization.

The follow-up duration is 3 months, and the visit schedule is as follows: Subjects enrolled based on randomization procedures will receive visits at screening/baseline period, first drug administration, immediately after reperfusion therapy(within 2 hours), 24 ± 2 hours, 96 ± 7 hours, 14 ± 2 days, 28 ± 2 days and 90 ± 7 days after randomization, and in case of any events.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangxi
      • Liuzhou, Guangxi, China
    • Hunan
      • Changsha, Hunan, China
        • Recruiting
        • Hunan Provincial People's Hospital
        • Contact:
          • Zhao Zhihong
        • Contact:
    • Jiangxi
      • Pingxiang, Jiangxi, China
        • Recruiting
        • Pingxiang People's Hospital
        • Contact:
          • Yi Fei
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  • 35 years old ≤ Age ≤ 80 years old
  • Patients with acute ischemic stroke was diagnosed within 24 hours of onset (time from onset to completion of reperfusion therapy)
  • Patients with first stroke or prior to stroke onset (mRS score 0-1)
  • Patients with acute large vessel occlusion (LVO) confirmed by imaging, including the responsible vessel was located in the intracranial internal carotid artery, the T-shaped branch, the M1/M2 segment of the middle cerebral artery, or the A1/A2 segment of the anterior cerebral artery
  • ASPECTS score ≥ 6
  • 6<NIHSS score ≤ 25 after the onset of this disease
  • Patients who meet the indications for reperfusion therapy, including mechanical thrombectomy, bridging therapy (intravenous r-tPA thrombolytic therapy), and plan to undergo mechanical thrombectomy
  • Patients or his/her legal representatives are able to understand and sign the informed consent

Exclusion criteria:

  • Severe consciousness disturbance: NIHSS 1a consciousness level ≥2 points
  • Patients with definite history of intracranial hemorrhage (such as subarachnoid hemorrhage, cerebral hemorrhage, etc.)
  • Patients with intracranial tumor, arteriovenous malformation, or aneurysm
  • Patients with bilateral anterior or posterior circulation ischemic stroke
  • Patients with large vascular occlusion of rare or unknown etiology, such as dissection, vasculitis, etc.
  • Patients who have received treatment with dual antiplatelet drugs, tirofiban, warfarin, novel oral anticoagulant, argatroban, snake venom, defibrase, lumbrokinase and other defibrase therapy after the onset of disease
  • Patients with severe hepatic insufficiency or renal insufficiency and received dialysis for various reasons before randomization (severe hepatic insufficiency is defined as ALT > 3 × ULN or AST >3 × ULN; severe renal insufficiency is defined as serum creatinine >3.0 mg/dL (265.2 μmol/L) or creatinine clearance < 30 mL/min)
  • Patients with haemorrhagic diathesis (including but not limited to): platelet count < 100 × 109/L; heparin treatment within the last 48 hours; taking oral warfarin; taking novel oral anticoagulant; administration with direct thrombin or Xa factor inhibitors; with hereditary hemorrhagic disorders, such as hemophilia
  • Patients with refractory hypertension that is difficult to be controlled by medication (systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg)
  • Patients with significant head trauma or stroke within 3 months prior to randomization
  • Patients who have received intracranial or spinal surgery within 3 months prior to randomization
  • Patients with history of major surgery or serious physical trauma within 1 month prior to randomization
  • Patients with hemorrhagic retinopathy
  • Male subjects (or their partners) or female subjects who had planned to have a child during the whole study period and within 3 months after the end of the study period or were unwilling to use one or more non-drug contraceptive methods (e.g., complete abstinence, condoms, ligation, etc.) during the study period
  • Patients with contraindications to known contrast agent or other contrast agents; subjects who are allergic to cilostazol or dexborneol
  • Patients who plan to receive other surgical or intervention therapy within 3 months, which might require discontinuation of the study drugs
  • Patients with advanced disease, leading to life expectancy of < 6 months
  • Patients who have received treatment of investigational drug or device within 3 months
  • Other conditions where it is not suitable for patients to participate in the clinical trial, such as inability to understand and/or follow the study procedures and/or follow-up schedule due to psychiatric disorders or cognitive/emotional disorders, or contraindications to thrombectomy or MRI, etc.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Y-6 sublingual tablets
Y-6 sublingual tablets (each tablet contains 25 mg cilostazol and 6 mg dexborneol) Manufacturer: Nanjing Neurodawn Pharmaceutical Co., Ltd.
Drug: Y-6 sublingual tablets
Take Y-6 sublingual tablets for 28 days continuously.
Placebo Comparator: Placebo tablets of Y-6 sublingual tablet
Y-6 strength: Placebo tablets of Y-6 sublingual tablet (each tablet contains 0 mg cilostazol and 0.06 mg dexborneol) Manufacturer: Nanjing Neurodawn Pharmaceutical Co., Ltd.
Drug: Placebo tablets of Y-6 sublingual tablet
Take Placebo tablets of Y-6 sublingual tablet for 28 days continuously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of mRS score recovered to 0~1 score
Time Frame: 90±7 days after randomization
The modified Rankin Scale (mRS) decreasing to 0~1 score. mRS Mainly measures patients' independent living ability, including physical function, activity ability and participation in daily life. A score of 0 on the mRS Scale indicates no symptoms and a score of 5 indicates severe disability.
90±7 days after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Integrity of BBB evaluated by DCE
Time Frame: 96±7 hours after randomization
BBB permeability is assessed by DCE-MRI
96±7 hours after randomization
Proportion of study patients with early progression of stroke at 24 ± 2 hours and 96 ± 7 hours after randomization
Time Frame: 24 ± 2 hours and 96 ± 7 hours after randomization
NIHSS score increasing by ≥ 2 points, or the score of hemiplegia increasing by≥1 point, or the score of conscious disturbance increasing by ≥ 1 point compared with baseline within 7 days of onset, and intracranial hemorrhage is excepted by CT or MRI. Exacerbations not attributable to stroke are also excluded such as cardiac failure, liver and renal failure, etc.
24 ± 2 hours and 96 ± 7 hours after randomization
Proportion of study patients with combined vascular events at 90 ± 7 days after randomization
Time Frame: 90 ± 7 days after randomization
Symptomatic stroke, myocardial infarction and vascular death
90 ± 7 days after randomization
The mRS score at 90±7 days after randomization
Time Frame: 90±7 days after randomization
The modified Rankin Scale (mRS) evaluated at 90±7 days after randomization. mRS Mainly measures patients' independent living ability, including physical function, activity ability and participation in daily life. A score of 0 on the mRS Scale indicates no symptoms and a score of 5 indicates severe disability.
90±7 days after randomization
Changes of NIHSS score between baseline and immediately after reperfusion therapy
Time Frame: immediately after reperfusion therapy (within 2 hours)
NIHSS score after reperfusion therapy within 2 hours changing compared with baseline NIHSS. The NIHSS score ranges from 0 to 42. The higher the score, the more severe the nerve damage.
immediately after reperfusion therapy (within 2 hours)
Changes of NIHSS score between baseline and at 24 ± 2 hours, 96 ± 7 hours, 14 ± 2 days and 28 ± 3days after randomization
Time Frame: 24 ± 2 hours, 96 ± 7 hours, 14 ± 2 days and 28 ± 3 days after randomization and baseline NIHSS score
NIHSS score changing compared with baseline NIHSS. The NIHSS score ranges from 0 to 42. The higher the score, the more severe the nerve damage.
24 ± 2 hours, 96 ± 7 hours, 14 ± 2 days and 28 ± 3 days after randomization and baseline NIHSS score

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Integrity evaluation of BBB by FEXI at 96 ± 7 hours after randomization
Time Frame: 96 ± 7 hours after randomization
BBB permeability is assessed by FEXI
96 ± 7 hours after randomization
Integrity evaluation of BBB by FEXI at 28 ± 3 days after randomization
Time Frame: 28 ± 3 days after randomization
BBB permeability is assessed by FEXI
28 ± 3 days after randomization
Differences of indicators of venous thrombotic inflammation (plasma sGPVI, sADAMTS 13, sCD40L levels) and indirect indicators of BBB disruption (MMP-9, S100B) between baseline and 14±2 days of randomization
Time Frame: 14±2 days of randomization compared with baseline
Collecting blood samples to evaluate venous thrombotic inflammation (plasma sGPVI, sADAMTS 13, sCD40L levels) and indirect indicators of blood-brain barrier disruption (MMP-9, S100B)
14±2 days of randomization compared with baseline
Differences of indicators of venous thrombotic inflammation (plasma sGPVI, sADAMTS 13, sCD40L levels) and indirect indicators of BBB disruption (MMP-9, S100B) between baseline and 24±2 hours of randomization
Time Frame: 24±2 hours of randomization compared with baseline
Collecting blood samples to evaluate venous thrombotic inflammation (plasma sGPVI, sADAMTS 13, sCD40L levels) and indirect indicators of blood-brain barrier disruption (MMP-9, S100B)
24±2 hours of randomization compared with baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Tiantan Hospital

Collaborators

NeuroDawn Pharmaceutical Co., Ltd.

Investigators

  • Principal Investigator: Yilong Wang, PhD，MD, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 5, 2023

Primary Completion (Estimated)

July 1, 2024

Study Completion (Estimated)

August 1, 2024

Study Registration Dates

First Submitted

April 19, 2023

First Submitted That Met QC Criteria

April 19, 2023

First Posted (Actual)

May 1, 2023

Study Record Updates

Last Update Posted (Actual)

September 28, 2023

Last Update Submitted That Met QC Criteria

September 27, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • YW2022-046-03

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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