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

NCT03691727 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 201805823
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Subarachnoid Hemorrhage, Aneurysmal

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Intracranial Hemorrhage (Symptomatic and Asymptomatic)

  The hypothesis is that the prevalence of intracranial hemorrhage (symptomatic and asymptomatic) 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.

  Day 1 to Day 7

• Number of Participants With Delayed Cerebral Ischemia /Clinical Vasospasm

  The measurement of then incidence of delayed cerebral ischemia /clinical vasospasm in Tirofiban/Aggrastat group vs. placebo

  Day 1 to Day 7

Study Arms (2)

tirofiban hydrochloride (AGGRASTAT®)

EXPERIMENTAL

tirofiban hydrochloride (AGGRASTAT®) administered continuously over the course of 7 days. MRI Neurological Exam Vital Signs Questionnaires

Drug: tirofiban hydrochloride (AGGRASTAT®); Diagnostic Test: MRI; Diagnostic Test: Neurological Exam; Behavioral: Questionnaires; Diagnostic Test: Vital Signs

Standard of Care Control Arm

ACTIVE COMPARATOR

Standard of Care Treatment MRI Neurological Exam Vital Signs Questionnaires

Diagnostic Test: MRI; Diagnostic Test: Neurological Exam; Behavioral: Questionnaires; Diagnostic Test: Vital Signs; Other: Standard of Care Treatment

Interventions

tirofiban hydrochloride (AGGRASTAT®) DRUG

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.

tirofiban hydrochloride (AGGRASTAT®)

MRI DIAGNOSTIC_TEST

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

Standard of Care Control Arm; tirofiban hydrochloride (AGGRASTAT®)

Neurological Exam DIAGNOSTIC_TEST

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

Standard of Care Control Arm; tirofiban hydrochloride (AGGRASTAT®)

Questionnaires BEHAVIORAL

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.

Standard of Care Control Arm; tirofiban hydrochloride (AGGRASTAT®)

Vital Signs DIAGNOSTIC_TEST

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.

Standard of Care Control Arm; tirofiban hydrochloride (AGGRASTAT®)

Standard of Care Treatment OTHER

Participants will receive standard of care treatment and will not receive study drug.

Standard of Care Control Arm

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• David Hasan: lead

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Related Publications (1)

• Zanaty M, Allan L, Samaniego EA, Piscopo A, Ryan E, Torner JC, Hasan D. Phase 1/2a Trial of ISPASM. Stroke. 2021 Dec;52(12):3750-3758. doi: 10.1161/STROKEAHA.121.034578. Epub 2021 Sep 2.

  PMID: 34470496 DERIVED

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Interventions

Tirofiban; Neurologic Examination; Surveys and Questionnaires; Vital Signs

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tyrosine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Diagnostic Techniques, Neurological; Diagnostic Techniques and Procedures; Diagnosis; Physical Examination; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Results Point of Contact

• Title: David Hasan
• Organization: University of Iowa

david-hasan@uiowa.edu

319-384-8669

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: All subjects will be randomized 2:1, Aggrastat vs. placebo.

Study Record Dates

• First Submitted: September 28, 2018
• First Posted: October 2, 2018
• Study Start: January 24, 2019
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2021
• Last Updated: January 10, 2022
• Results First Posted: October 4, 2021

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)