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Neovascularization Induced by Mechanical Barrier disrUption and Systemic Erythropoietin in Patients With Cerebral Perfusion Deficits (NIMBUS)

Primary Purpose

Angiogenesis, Ischemic Stroke

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
erythropoietin
Sponsored by
Ajou University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Angiogenesis

Eligibility Criteria

19 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • age 20~85
  • Acute period (ischemic stroke confirmation on DWI or TIA within 14 days after symptom onset)
  • Below 20 point of initial NIHSS score within 14 days after stroke onset and enrolment.
  • Confirmation of atherosclerotic or steno-occlusive stroke mechanism (proximal cerebral arteries) on CTA or MRA .
  • At least hemodynamically, perfusion status of a candidate is stage II or III (decrease of regional Cerebral blood flow on CBF map), moyamoya disease
  • If female then not of childbearing potential
  • Informed consent

Exclusion Criteria:

  • Primary intracerebral haemorrhage (ICH), or parenchymal haemorrhagic transformation of infarction (type PHI or PHII as defined in ECASS), subarachnoid haemorrhage (SAH), arterio-venous malformation (AVM), cerebral aneurysm, or cerebral neoplasm
  • Treated with a thrombolytic <24 hours (if >24 hours and excluded ICH then eligible)
  • Score >=1 on the NIHSS item 1a
  • Pre-stroke mRS score <2
  • Uncontrolled hypertension(irregularity systollic BP > 150mmHg
  • Previous treatment with erythropoietin
  • At screening: Hemoglobin >14 g/dl, prolonged PT or PTT, serum Cr >2.0 ,mg/dl, BUN >40, thrombocytopenia or neutropenia as defined by the lower limit of normal for the platelet count or white blood cell count, respectively (absolute neutrophil count of > 1800/mm3 required for participation), or > 2 times of normal on liver function tests (SGOT, SGPT, total bilirubin)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    No Intervention

    Arm Label

    Group A

    Group B

    Arm Description

    mechanical barrier disruption procedure + hrEPO manufactured by Dong-A pharmaceutics Multiple burrholes with local anesthesia after medication Drug: Erythropoietin 33,000u daily for 3 day via intravenous

    mechanical barrier disruption procedure Drug: no-specific intervention

    Outcomes

    Primary Outcome Measures

    Successful new vascularization of internal-to-external cerebral collateral flow
    transdural neovascularization: absent vs. present) from 6- vessel angiography

    Secondary Outcome Measures

    Early Neurological Deterioration (END) during admission
    NIHSS scores are daily assessed during admission and neurological deterioration is designated as at least 2-point decrease of NIHSS during 14 days after admission
    Adverse events during the study period
    Overall adverse events (early neurological deterioration; adverse events within 7 days after operation; and adverse events during the study period

    Full Information

    First Posted
    November 10, 2015
    Last Updated
    August 17, 2020
    Sponsor
    Ajou University School of Medicine
    Collaborators
    Dong-A Pharmaceutical Co., Ltd.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02603406
    Brief Title
    Neovascularization Induced by Mechanical Barrier disrUption and Systemic Erythropoietin in Patients With Cerebral Perfusion Deficits
    Acronym
    NIMBUS
    Official Title
    Neovascularization Induced by Mechanical Barrier disrUption and Systemic Erythropoietin in Patients With Cerebral Perfusion Deficits (NIMBUS Trial)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2020
    Overall Recruitment Status
    Completed
    Study Start Date
    July 15, 2016 (Actual)
    Primary Completion Date
    July 16, 2019 (Actual)
    Study Completion Date
    December 31, 2019 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Ajou University School of Medicine
    Collaborators
    Dong-A Pharmaceutical Co., Ltd.

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Neovascularization Induced by Mechanical Barrier disrUption and Systemic erythropoietin in patients with cerebral perfusion deficits (NIMBUS trial)

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Angiogenesis, Ischemic Stroke

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    Care ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    44 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Group A
    Arm Type
    Experimental
    Arm Description
    mechanical barrier disruption procedure + hrEPO manufactured by Dong-A pharmaceutics Multiple burrholes with local anesthesia after medication Drug: Erythropoietin 33,000u daily for 3 day via intravenous
    Arm Title
    Group B
    Arm Type
    No Intervention
    Arm Description
    mechanical barrier disruption procedure Drug: no-specific intervention
    Intervention Type
    Drug
    Intervention Name(s)
    erythropoietin
    Other Intervention Name(s)
    eporon
    Primary Outcome Measure Information:
    Title
    Successful new vascularization of internal-to-external cerebral collateral flow
    Description
    transdural neovascularization: absent vs. present) from 6- vessel angiography
    Time Frame
    6 months
    Secondary Outcome Measure Information:
    Title
    Early Neurological Deterioration (END) during admission
    Description
    NIHSS scores are daily assessed during admission and neurological deterioration is designated as at least 2-point decrease of NIHSS during 14 days after admission
    Time Frame
    14 days
    Title
    Adverse events during the study period
    Description
    Overall adverse events (early neurological deterioration; adverse events within 7 days after operation; and adverse events during the study period
    Time Frame
    up to 6 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    19 Years
    Maximum Age & Unit of Time
    85 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: age 20~85 Acute period (ischemic stroke confirmation on DWI or TIA within 14 days after symptom onset) Below 20 point of initial NIHSS score within 14 days after stroke onset and enrolment. Confirmation of atherosclerotic or steno-occlusive stroke mechanism (proximal cerebral arteries) on CTA or MRA . At least hemodynamically, perfusion status of a candidate is stage II or III (decrease of regional Cerebral blood flow on CBF map), moyamoya disease If female then not of childbearing potential Informed consent Exclusion Criteria: Primary intracerebral haemorrhage (ICH), or parenchymal haemorrhagic transformation of infarction (type PHI or PHII as defined in ECASS), subarachnoid haemorrhage (SAH), arterio-venous malformation (AVM), cerebral aneurysm, or cerebral neoplasm Treated with a thrombolytic <24 hours (if >24 hours and excluded ICH then eligible) Score >=1 on the NIHSS item 1a Pre-stroke mRS score <2 Uncontrolled hypertension(irregularity systollic BP > 150mmHg Previous treatment with erythropoietin At screening: Hemoglobin >14 g/dl, prolonged PT or PTT, serum Cr >2.0 ,mg/dl, BUN >40, thrombocytopenia or neutropenia as defined by the lower limit of normal for the platelet count or white blood cell count, respectively (absolute neutrophil count of > 1800/mm3 required for participation), or > 2 times of normal on liver function tests (SGOT, SGPT, total bilirubin)

    12. IPD Sharing Statement

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    Neovascularization Induced by Mechanical Barrier disrUption and Systemic Erythropoietin in Patients With Cerebral Perfusion Deficits

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