Tirofiban Plus Intravenous Thrombolysis in Acute Anterior Choroidal Infarction or Paramedian Pontine Infarction (TITACIPPI)

Efficacy of Simultaneous Infusion of Tirofiban With Intravenous Thrombolysis in Patients With Acute Anterior Choroidal Infarction or Paramedian Pontine Infarction

TITACIPPI (Tirofiban with Intravenous Thrombolysis in Acute Anterior Choroidal Infarction [ACI] and Paramedian Pontine Infarction [IPP]) study aimed to evaluate the efficacy and safety of simultaneous infusion of tirofiban with intravenous thrombolysis (IVT + tirofiban group) compared to IVT alone (IVT alone group) in patients with ACI or PPI. TITACIPPI study is a retrospective, single-center observational study conducted from March 01, 2014, to December 31, 2022.

Study Overview

• Status: Completed
• Conditions: Acute Anterior Choroidal Infarction (ACI); Paramedian Pontine Infarction (IPP)
• Intervention / Treatment: Procedure: IVT with tenecteplase or alteplase; Procedure: Intervention Name : Tirofiban and IVT with tenecteplase or alteplase

Detailed Description

ACI and PPI are frequently associated with clinical fluctuations, characterized by recurrent transient more or less regressive stereotyped episodes of focal motor deficits affecting the face, arm, and leg, and finally with a risk of lasting neurological worsening that can lead to definite residual neurological disability. These ischemic strokes (ACI and PPI) are not very sensitive to IVT, thus 26% to 48% will experience neurological aggravation despite the administration of this treatment. Studies in Asia have shown a possible clinical benefit of simultaneous infusion of tirofiban with IVT in patients with ischemic stroke of atheromatous or microatheromatous origin without additional bleeding risk. To date, no studies have tested the efficacy of simultaneous infusion of tirofiban and IVT in the well-defined subgroup of ACI and PPI and a non-Asian population.

• Study Type: Observational
• Enrollment (Actual): 48

Contacts and Locations

Study Locations

• France
  • Corbeil-Essonnes, France, 91106
    • Centre Hospitalier Sud Francilien

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study included all patients aged ≥ 18 years with ACI or PPI, negative on FLAIR of the MRI of pretreatment, who had received IVT alone or simultaneous infusion of tirofiban with IVT in the stroke unit of CHSF between March 1, 2014, and December 31, 2022.

Description

Inclusion Criteria:

• Patients aged ≥ 18 years with ACI or PPI between March 01, 2014 and December 31, 2022.
• Patients hospitalized in the stroke unit of Centre Hospitalier Sud Francilien in the acute phase of their ischemic stroke (FLAIR negative on the pre-treatment brain MRI allowing IVT).
• Patients with NIHSS ≥ 2 on admission
• Patients treated with IVT
• For the experimental group: patients treated with tirofiban at 0.4 μg/kg/min with the start of infusion within 1 hour of IVT initiation.
• Patients with post-treatment brain MRI within 24-36h.

Exclusion Criteria:

• Patients with contraindications to IVT (cardiac, thoracic or digestive surgery less than 14 days old, thrombocytopenia < 100,000/mm3, etc.).
• Absence of MRI as initial imaging.
• Less than 24 hours of continuous infusion of tirofiban.
• Patients at high risk of cerebral hemorrhage: severe microangiopathy (Fazekas Score 3), microbleeds > 5, or leptomeningeal hemosiderosis suggestive of amyloid angiopathy.
• Patients with pre-stroke mRS ≥ 3.
• Patients informed of the research and objecting to the collection of their data.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Intravenous thrombolysis (IVT); group of patients treated with IVT alone	Procedure: IVT with tenecteplase or alteplase; Patients received intravenous tenecteplase 0.25mg/kg (maximum dose: 25mg), administered as a bolus over 5 to 10 seconds or intravenous alteplase 0.9 mg/kg (maximum dose: 90mg), 10% as bolus and the remainder as continuous perfusion over 1 hour.
Tirofiban + IVT; groups of patients treated with simultaneous infusion of tirofiban and IVT	Procedure: Intervention Name : Tirofiban and IVT with tenecteplase or alteplase; IVT with tenecteplase or alteplase with continuous infusion of tirofiban 0.4µg/kg/min continued for 24 to 48 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volume of the ischemic lesion	Evolution of the volume of the ischemic lesion in diffusion-weighted imaging between initial MRI and post-therapy MRI	at 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS)	Proportion of the patients with mRS 0-2	at 3 months
Secondary neurological deterioration	Rate of secondary neurological deterioration (fluctuations or neurological progression defined as an increase of at least 1 point in NIHSS).	at 72 hours
Cerebral hemorrhages	Rates of cerebral hemorrhages defined according to the Heidelberg Bleeding Classification	at 24 hours
Systemic bleedings	Rate of significant systemic bleeding (i.e., requiring specific treatment).	at 24 hours
NIHSS	NIHSS (from 0=favorable to 42=unfavorable)	at day 7

Collaborators and Investigators

• Sponsor: Centre Hospitalier Sud Francilien

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2023
• Primary Completion (Actual): September 13, 2023
• Study Completion (Actual): September 13, 2023

Study Registration Dates

• First Submitted: February 8, 2023
• First Submitted That Met QC Criteria: February 8, 2023
• First Posted (Actual): February 17, 2023

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: tirofiban; intravenous thrombolysis; anterior choroidal infarction; paramedian pontine infarction
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Brain Infarction; Infarction; Brain Stem Infarctions; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Tirofiban; Tissue Plasminogen Activator; Tenecteplase
• Other Study ID Numbers: 2022/0039

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No