Induced Suppression of Platelet Activity in Aneurysmal Subarachnoid Hemorrhage Management-2 (iSPASM-2)

NCT07493577 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: Pro00119469UG3NS138219
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 2

Brief Summary

An exploratory, randomized, double-blinded, placebo-controlled, two-center clinical trial to determine the maximum tolerated dosage of intravenous tirofiban in patients with aneurysmal subarachnoid hemorrhage (aSAH) post-endovascular coiling. The study will also assess pharmacology and safety, with exploratory endpoints including delayed cerebral ischemia (DCI), vasospasm, and functional outcomes.

Conditions

Aneurysmal Subarachnoid Hemorrhage

Keywords

Subarachnoid Hemorrhage; Delayed Cerebral Ischemia; Tirofiban; Brain Aneurysm Rupture

Outcome Measures

Primary Outcomes (1)

• Tirofiban dosage-limiting toxicity (DLT)

  Presence of any of the following: any intracranial hemorrhage, major extracranial hemorrhage (defined as clinically overt bleeding leading to death; OR clinically overt bleeding causing a reduction in hemoglobin of ≥2g/dl; OR clinically overt bleeding necessitating transfusion of ≥2 units of packed red cells or whole blood; OR clinically overt bleeding in a critical area or organ other than the intracranial compartment (including intraspinal, intraocular, pericardial, intra-articular, retroperitoneal, intramuscular \[with compartment syndrome\])), thrombocytopenia, or serious adverse event (SAE) due to tirofiban.

  Within 14 days post-randomization

Secondary Outcomes (7)

• Pharmacokinetic parameters - total clearance (Cltot)

  Up to 7 hours after drug discontinuation

• Pharmacokinetic parameters - Volume of distribution (Vd)

  Up to 7 hours after drug discontinuation

• Pharmacokinetic parameters - Maximum (peak) plasma concentration (Cmax)

  Up to 7 hours after drug discontinuation

• Pharmacokinetic parameters - Minimum (trough) plasma concentration (Cmin)

  Up to 7 hours after drug discontinuation

• Pharmacokinetic parameters - Average Plasma Concentration (Cavg)

  Up to 7 hours after drug discontinuation

Other Outcomes (12)

• Delayed cerebral ischemia (DCI) or death without DCI

  Within 14 days post-randomization

• Cerebral vasospasm

  Within 14 days post-randomization or until discharge from the index admission, which occurred later

• Mortality

  3 and 6 months post-randomization

Study Arms (2)

Tirofiban

EXPERIMENTAL

Continuous IV infusion of tirofiban for 1, 3, 5, or 7 days post-endovascular coiling.

Drug: Tirofiban

Placebo

PLACEBO COMPARATOR

Continuous IV infusion of saline placebo for 1, 3, 5, or 7 days post-endovascular coiling.

Drug: Placebo

Interventions

Tirofiban DRUG

IV infusion at 0.10 microgram/kilogram/minute (mcg/kg/min) for 1 day, 3 days, 5 days, or 7 days according to the dose escalation procedure.

Also known as: Aggrastat ®

Tirofiban

Placebo DRUG

IV infusion at the same infusion duration as the study drug; same adjustments

Also known as: Normal Saline

Placebo

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 18-85
• Baseline Modified Rankin Scale (mRS) 0-3 (pre-SAH)
• SAH attributed to ruptured cerebral aneurysm
• Admission Computed Tomography (CT) scan shows Modified Fisher grade 1-4 due to aSAH primarily in the supratentorial space
• World Federation of Neurosurgical Societies (WFNS) scale grade ≤4 at randomization
• Onset of symptoms of aSAH (ictus) occurred \<72 hours prior to presentation
• If External Ventricular Drain (EVD) placed, placement is ≥12 hours prior to enrollment
• All aneurysm(s) suspected to be responsible for the hemorrhage must be secured via Endovascular Coil Embolization with a post-embolization Raymond-Roy Score of 1 (Complete) or 2 (Residual Neck) prior to enrollment
• Participant can be randomized within 48 hours of aneurysm treatment
• Participant or participant's legally-authorized representative (LAR) has provided documented informed consent

You may not qualify if:

• Angio-negative SAH, defined as a SAH with a digital subtraction angiogram that does not show an intracranial aneurysm
• Surgical clipping prior of the ruptured aneurysm or any non-ruptured aneurysm on the same admission to enrollment
• Remaining untreated aneurysm(s) that could reasonably be considered a possible alternate cause of the aSAH based on the observed bleeding pattern
• Uncontrollable hypertension (\>180 systolic and/or \>110 diastolic) that is not correctable prior to enrollment
• Active internal bleeding, or history of bleeding diathesis, major surgical procedure, or severe physical trauma within the previous month (30 days)
• A medical diagnosis that requires continuous use of aspirin, clopidogrel, ticagrelor, or tirofiban during the study drug infusion
• New parenchymal hemorrhage or new infarction larger than 15 cubic centimeters (cc) in volume by CT
• Thrombolytic therapy within 24 hours prior to enrollment (alteplase, tenecteplase, or urokinase)
• Previous intracranial hemorrhage, intracranial neoplasm, subarachnoid hemorrhage, or arterial-venous malformation
• Thrombocytopenia (platelet count \<100,000/microliter (µL) assuming clumping is ruled out
• Allergy or intolerance to tirofiban
• Pregnant or lactating
• Chronic kidney disease with creatinine clearance (CrCl ≤ 30 milliliters per minute \[ml/min\]) or acute kidney injury (AKI) at study screening. AKI is defined as:
• i) Increase in serum creatinine by 0.3 milligrams per deciliter (mg/dL) or more (26.5 micromoles per liter \[μmol/L\] or more) within 48 hour period; OR ii) Increase in serum creatinine to 1.5 times or more than the baseline of the prior 7 day period; OR iii) Urine volume less than 0.5 ml/kg/hour for at least 6 hours

Sponsors & Collaborators

• Dr David Hasan, M.D.: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (2)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

University of Texas Health Sciences Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Interventions

Tirofiban; Saline Solution

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; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Emad Hasan, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Brian Mac Grory, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hazani Benitez-Rosas

CONTACT

919-681-4974; hazani.benitez-rosas@duke.edu

Beth Perry

CONTACT

919-681-2695; beth.perry@duke.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, study team, and clinical team will be blinded to study drug. A medical safety officer overseeing the trial will not be blinded for safety reviews. If indicated, emergency unmasking will be performed.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurosurgery

Study Record Dates

• First Submitted: March 10, 2026
• First Posted: March 25, 2026
• Study Start (Estimated): July 23, 2026
• Primary Completion (Estimated): January 23, 2029
• Study Completion (Estimated): January 23, 2032
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)