Subarachnoid Hemorrhage, AneurysmalPhase 1/2NCT03691727
Induced Suppression of Platelets Activity in Aneurysmal SAH Management (iSPASM)
A Phase 1/2 study testing tirofiban hydrochloride (AGGRASTAT®), MRI and Neurological Exam in people with Subarachnoid Hemorrhage, Aneurysmal, run by David Hasan at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Subarachnoid Hemorrhage, Aneurysmal
- What is being tested?
- tirofiban hydrochloride (AGGRASTAT®), MRI and Neurological Exam
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jan 2019to 1 Jul 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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:
- active internal bleeding or a history of bleeding diathesis within the previous 30 days
- A history of thrombocytopenia following prior exposure to AGGRASTAT
- history, symptoms, or findings suggestive of aortic dissection
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1/2a Exploratory Clinical Trial: Induced Suppression of Platelets Activity in Aneurysmal SAH Management (iSPASM)
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.
Read the 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.
- Conditions
- Subarachnoid Hemorrhage, Aneurysmal
- Being tested
- tirofiban hydrochloride (AGGRASTAT®), MRI, Neurological Exam, Questionnaires, Vital Signs
- Medical subject headings
- Subarachnoid Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
MRIDiagnostic test
Participants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes.
Neurological ExamDiagnostic test
Neurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits.
QuestionnairesBehavioural
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.
Vital SignsDiagnostic 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 TreatmentOther
Participants will receive standard of care treatment and will not receive study drug.
| Study group | Role | What they receive |
|---|---|---|
| tirofiban hydrochloride (AGGRASTAT®) | Experimental | tirofiban hydrochloride (AGGRASTAT®) administered continuously over the course of 7 days.
MRI Neurological Exam Vital Signs Questionnaires Receives: 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 Receives: Diagnostic Test: MRI; Diagnostic Test: Neurological Exam; Behavioral: Questionnaires; Diagnostic Test: Vital Signs; Other: Standard of Care Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: Day 1 to Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2018
- Study start24 Jan 2019
- Primary completion1 Jul 2020
- Study completion1 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Subarachnoid Hemorrhage, AneurysmalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- All subjects will be randomized 2:1, Aggrastat vs. placebo.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Hasan
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, David Hasan, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03691727
- Sponsor's protocol ID
- 201805823
- Status last verified
- Aug 2020
- First submitted
- 28 Sep 2018
- Last updated
- 10 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34470496
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2a Exploratory Clinical Trial: Induced Suppression of Platelets Activity in Aneurysmal SAH Management (iSPASM)
- ClinicalTrials.gov ID
- NCT03691727
- Acronym / sponsor ID
- 201805823
- Conditions
- Subarachnoid Hemorrhage, Aneurysmal
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- David HasanUniversity, hospital or other
- Study start
- 24 Jan 2019 (actual)
- Primary completion
- 1 Jul 2020 (actual)
- Study completion
- 1 Jul 2021 (actual)
- First posted
- 2 Oct 2018 (actual)
- Results
- Posted 4 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- All subjects will be randomized 2:1, Aggrastat vs. placebo.
| Arm | Type | Receives |
|---|---|---|
| tirofiban hydrochloride (AGGRASTAT®) | Experimental | Drug: tirofiban hydrochloride (AGGRASTAT®), Diagnostic Test: MRI, Diagnostic Test: Neurological Exam, Behavioral: Questionnaires, Diagnostic Test: Vital Signstirofiban hydrochloride (AGGRASTAT®) administered continuously over the course of 7 days. MRI Neurological Exam Vital Signs Questionnaires |
| Standard of Care Control Arm | Active comparator | Diagnostic Test: MRI, Diagnostic Test: Neurological Exam, Behavioral: Questionnaires, Diagnostic Test: Vital Signs, Other: Standard of Care TreatmentStandard of Care Treatment MRI Neurological Exam Vital Signs Questionnaires |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (30 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | tirofiban hydrochloride (AGGRASTAT®) |
| MRIParticipants will undergo 2 MRIs administered within 24 hours post Coil Embolization procedure and prior to discharge to monitor for ischemic changes. | Diagnostic test | Standard of Care Control Arm, tirofiban hydrochloride (AGGRASTAT®) |
| Neurological ExamNeurological exams will be done at screening, randomization, days 2-7, discharge, 6 week, 6 month, and one year follow up visits. | Diagnostic test | Standard of Care Control Arm, tirofiban hydrochloride (AGGRASTAT®) |
| QuestionnairesQuality 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. | Behavioural | Standard of Care Control Arm, tirofiban hydrochloride (AGGRASTAT®) |
| Vital SignsVital 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. | Diagnostic test | Standard of Care Control Arm, tirofiban hydrochloride (AGGRASTAT®) |
| Standard of Care TreatmentParticipants will receive standard of care treatment and will not receive study drug. | Other | Standard of Care Control Arm |
Primary outcome
Number of Participants With Intracranial Hemorrhage (Symptomatic and Asymptomatic)
Time frame: Day 1 to Day 7
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.
Number of Participants With Delayed Cerebral Ischemia /Clinical Vasospasm
Time frame: Day 1 to Day 7
The measurement of then incidence of delayed cerebral ischemia /clinical vasospasm in Tirofiban/Aggrastat group vs. placebo
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34470496Zanaty 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing tirofiban hydrochloride (AGGRASTAT®), MRI and Neurological Exam in people with Subarachnoid Hemorrhage, Aneurysmal, run by David Hasan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Intracranial Hemorrhage (Symptomatic and Asymptomatic) (time frame: Day 1 to Day 7). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03691727, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2022.