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Induced Suppression of Platelets Activity in Aneurysmal SAH Management (iSPASM)

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ClinicalTrials.gov Identifier: NCT03691727
Recruitment Status : Recruiting
First Posted : October 2, 2018
Last Update Posted : June 11, 2019
Sponsor:
Information provided by (Responsible Party):
David Hasan, University of Iowa

Brief Summary:
This is a phase 1/2a, randomized, double blind, single-center study comparing standard care alone to standard care with Aggrastat in patients diagnosed with aneurysmal subarachnoid hemorrhage.

Condition or disease Intervention/treatment Phase
Subarachnoid Hemorrhage, Aneurysmal Drug: tirofiban hydrochloride (AGGRASTAT®) Diagnostic Test: MRI Diagnostic Test: Neurological Exam Behavioral: Questionnaires Diagnostic Test: Vital Signs Other: Standard of Care Treatment Phase 1 Phase 2

Detailed Description:

This is a phase 1/2a, randomized, double blind, single-center study comparing standard care alone to standard care with Aggrastat in patients diagnosed with aneurysmal subarachnoid hemorrhage. The investigational plan is to explore the safety profile of Aggrastat administered continuously over 7 days, beginning at least 12 hours after a clinically indicated Endovascular Coil Embolization procedure.

As a part of the study, qualifying subjects will undergo two MRI scans, one at baseline and again prior to discharge. A neurological exam and vital signs will be administered at baseline, daily during drug administration, and at follow-up visits. Additional assessments include administration of the following questionnaires: mRS score, IADL, and QOLIBRI-OS.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 282 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: All subjects will be randomized 2:1, Aggrastat vs. placebo.
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1/2a Exploratory Clinical Trial: Induced Suppression of Platelets Activity in Aneurysmal SAH Management (iSPASM)
Actual Study Start Date : January 24, 2019
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arm Intervention/treatment
Experimental: tirofiban hydrochloride (AGGRASTAT®)

tirofiban hydrochloride (AGGRASTAT®) administered continuously over the course of 7 days.

MRI Neurological Exam Vital Signs Questionnaires

Drug: tirofiban hydrochloride (AGGRASTAT®)
Participants will have intravenous Aggrastat administered continuously over the course of 7 days in the setting of subarachnoid hemorrhage at least 12 hours post clinically indicated Endovascular Coil Embolization procedure.

Diagnostic Test: MRI
Participants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes.

Diagnostic Test: Neurological Exam
Neurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits.

Behavioral: Questionnaires
Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS) and the Lawton Instrumental Activities of Daily Living (IADL) will be administered at 6 month and 1 year follow up visits.

Diagnostic Test: Vital Signs
Vital signs which include temperature, respiration rate, blood pressure and O2 stats will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits.

Active Comparator: Standard of Care Control Arm
Standard of Care Treatment MRI Neurological Exam Vital Signs Questionnaires
Diagnostic Test: MRI
Participants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes.

Diagnostic Test: Neurological Exam
Neurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits.

Behavioral: Questionnaires
Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS) and the Lawton Instrumental Activities of Daily Living (IADL) will be administered at 6 month and 1 year follow up visits.

Diagnostic Test: Vital Signs
Vital signs which include temperature, respiration rate, blood pressure and O2 stats will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits.

Other: Standard of Care Treatment
Participants will receive standard of care treatment and will not receive study drug.




Primary Outcome Measures :
  1. Symptomatic Hemorrhage [ Time Frame: Day 1 compared to Day 7 ]
    The risk of symptomatic hemorrhage secondary to ventriculostomy/VPS placement during the course of Aggrastat use is within 10% difference when compared to control using Day 1 and Day 7 non-contrast head CT to determine.

  2. Asymptomatic Hemorrhage [ Time Frame: Day 1 compared to Day 7 ]
    The risk of asymptomatic hemorrhage secondary to ventriculostomy/VPS placement during the course of Aggrastat use is within 30% difference when compared to control using Day 1 and Day 7 non-contrast head CT to determine.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 and ≤ 85 years
  • Hunt and Hess scale ≤ 4 at time of admission or following EVD placement.
  • CT showing modified Fisher grade 1-4 aSAH on admission.
  • The Modified Fisher CT rating scale: Grade 1 (minimal or diffuse thing SAH without IVH); Grade 2 (minimal or thin SAH with IVH), Grade 3 (thick cisternal clot without IVH), Grade 4 (thick cisternal clot with IVH)
  • Placement of EVD on admission.
  • Diagnosis of aSAH occurred < 24 hours prior to presentation at the treating facility.
  • Initiation of aneurysm securement procedure occurred ≤ 24 hours from admission to the treating facility.
  • All aneurysm(s) suspected to be responsible for the hemorrhage or potentially responsible for the hemorrhage must be secured in the following manner prior to enrollment: Endovascular Coil Embolization with a post-embolization Raymond-Roy Score of 1 (Complete) or 2 (Residual Neck)
  • Ability to screen the patient and obtain head CT, CT perfusion, and CCTA on admission, a head CT following EVD placement, during EVD weaning period and following VP shunt placement.
  • No evidence of a significant new focal neurological deficit after the angiogram, including monoparesis / monoplegia, hemiparesis / hemiplegia, or receptive, expressive, or global aphasia. Minor cranial nerve defect without any other new findings is permissible. The treating physician should use their best clinical judgement as to whether a significant neurological decline has occurred due to the procedure.
  • Patient or their Legally Authorized Representative (LAR) has provided written informed consent.

Exclusion Criteria:

  • Angio-negative SAH, defined as a subarachnoid hemorrhage with an angiogram that does not show a related intracranial hemorrhage.
  • A likely hemorrhage event preceding the ictus due to the increased risk of early vasospasm. Prior sentinel headache with negative CT or prior sentinel headache where the patient did not seek medical attention does not exclude the patient.
  • Surgical clipping of the ruptured aneurysm or any non-ruptured aneurysm on the same admission prior to enrollment.
  • SAH not caused by aneurysm rupture or aneurysm is identified to be traumatic, mycotic, blister or fusiform type by catheter angiography.
  • Any intracranial stent placement or non-coil intra-aneurysmal device (i.e., stent- assisted coiling with Neuroform, Enterprise, LVIS, LVIS Jr, Barrel Stent, Pulse Rider, LUNA, Medina or a similar device) where the stent device is implanted to treat the ruptured aneurysm.
  • A medical diagnosis that requires continuous use of clopidogrel, ticagrelor, or tirofiban during study drug infusion.
  • Antiplatelet therapy using clopidogrel, ticagrelor or tirofiban during the endovascular procedure that continues > 24 post embolization.
  • Multiple aneurysms that may have been untreated and a potential etiology for rupture.
  • Femoral arteriotomy stick above the inferior epigastric artery OR angiographic, CT, or clinical evidence of an arteriotomy related retroperitoneal hematoma or large flank hematoma. A stable groin hematoma is not an exclusion.
  • Thrombocytopenia (platelet count less than 100,000 - assuming clumping has been ruled out as a cause), confirmed active disseminated intravascular coagulation (DIC) at the time of enrollment OR a documented history of coagulopathy or bleeding diathesis.
  • New parenchymal hemorrhage or new infarction larger the 15cc in volume (clinically significant), or worsening midline shift as seen on the post-coiling, pre-enrollment head CT when compared to baseline admission head CT. New hyperdensity on CT scan related to contrast staining is not an exclusion.
  • Patient developed SAH-induced cardiac stunning prior to enrollment, with an ejection fraction < 40%.
  • Thrombolytic therapy within 24 hours prior to enrollment (rtPA, urokinase, etc.)
  • Concurrent significant intracranial pathology identified prior to enrollment, including but not limited to, Moyamoya disease, high suspicion or documented CNS vasculitis, severe fibromuscular dysplasia, arteriovenous malformation, arteriovenous fistula, significant cervical or intracranial atherosclerotic stenotic disease ≥ 70%, or malignant brain tumor.
  • Known seizure or epilepsy disorder (diagnosed prior to this aSAH diagnosis) where anti-epileptic medication was previously taken by the patient or have been recommended to be taken by the patient. Childhood seizures that have resolved and no longer require treatment are not part of this exclusion criteria.
  • Serious co-morbidities that could confound study results including but not limited to: Multiple Sclerosis, dementia, severe major depression, cancer likely to cause death in 2 years, multi-system organ failure, or any other conditions that could cause any degree of cognitive impairment.
  • Immunosuppression therapy including chronic corticosteroid usage.
  • Remote history of previous ruptured cerebral aneurysm.
  • History of gastrointestinal hemorrhage or major systemic hemorrhage within 30 days, hemoglobin less than 8 g/dL, INR ≥ 1.5, severe liver impairment defined as AST, ALT, AP, GGT > 2 x normal.
  • Creatinine clearance < 30 mL/min.
  • Major surgery within 30 days with contraindication to antiplatelet therapy.
  • Currently pregnant.
  • Contraindication for MRI
  • Contraindication to antiplatelet tirofiban:

    1. active internal bleeding or a history of bleeding diathesis within the previous 30 days
    2. A history of thrombocytopenia following prior exposure to AGGRASTAT
    3. history, symptoms, or findings suggestive of aortic dissection
    4. acute pericarditis
  • Actual Body Weight > 150 kg (due to the lack of safety data)
  • 2 or more passes for the ventricular catheter at time of placement.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03691727


Contacts
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Contact: David Hasan, MD (319) 384-8669 david-hasan@uiowa.edu
Contact: Debra OConnell Moore, MBA 319-356-1693 debra-oconnell-moore@uiowa.edu

Locations
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United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Lauren Allan, MD    319-356-7892    lauren-allan@uiowa.edu   
Contact: Debra OConnell Moore, MBA    319-356-1693    debra-oconnell-moore@uiowa.edu   
Principal Investigator: David Hasan, MD         
Sponsors and Collaborators
David Hasan

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Responsible Party: David Hasan, Principal Investigator, University of Iowa
ClinicalTrials.gov Identifier: NCT03691727     History of Changes
Other Study ID Numbers: 201805823
First Posted: October 2, 2018    Key Record Dates
Last Update Posted: June 11, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Hemorrhage
Subarachnoid Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Tirofiban
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors