Early Recanalization After Intravenous Thrombolysis With Tenecteplase Versus Alteplase in Distal Vessel Occlusion Strokes (DISTAL-IVT)

Early Successful Recanalization After Intravenous Thrombolysis With Tenecteplase Versus Alteplase in Distal Vessel Occlusion Strokes

The purpose of this monocentric retrospective study is to compare, in patients with acute distal vessel occlusion stroke, the early rates of successful recanalization in patients treated with Alteplase (ALT) versus Tenecteplase (TNK), based on a retrospective analysis of magnetic resonance imaging (MRI) performed early after IVT.

Study Overview

• Status: Recruiting
• Conditions: Acute Distal Vessel Occlusion Stroke
• Intervention / Treatment: Drug: Alteplase (0.9mg/kg); Drug: Tenecteplase (0.25mg/kg)

Detailed Description

Early rates of successful recanalization (SR) of distal vessel occlusions (DVO) following intravenous thrombolysis (IVT) between alteplase (ALT) and tenecteplase (TNK) are poorly known.

From March 2016 to February 2020, consecutive stroke patients hospitalized in the stroke unit of the Sud-Francilien Hospital with DVO identified on baseline MRI and suitable for IVT but not for mechanical thrombectomy will be included. In our stroke unit, patients were treated with ALT, 0.9 mg/kg from March 2016 to February 2018 and then with TNK, 0.25 mg/kg from March 2018 to February 2020. MRI was controlled 1-2 hours within IVT (MRI-2). Early recanalization was assessed on an adapted Arterial Occlusion Lesion (AOL) scale, SR being defined as AOL 2/3 scores on MRI-2. The rate reduction of thrombus length (TL) when thrombus persisted, the IVT response threshold of TL and the infarct size evolution were also assessed. In the present study, the investigators sought to compare early rates of SR between the two lytics, based on a retrospective analysis of magnetic resonance imaging (MRI) performed early after IVT.

• Study Type: Observational
• Enrollment (Estimated): 481

Contacts and Locations

• Study Contact: Name: Nicolas CHAUSSON, PHD; Phone Number: +33 1 61 69 77 11; Email: nicolas.chausson@chsf.fr
• Study Contact Backup: Name: Caroline TOURTE; Phone Number: +33 1 61 69 31 50; Email: caroline.tourte@chsf.fr

Study Locations

• France
  • Corbeil-Essonnes, France, 91106
    • Recruiting
    • Centre Hospitalier Sud Francilien
    • Contact: Nicolas CHAUSSON; Phone Number: +33161697711; Email: nicolas.chausson@chsf.fr
    • Contact: Didier SMADJA, MD; Phone Number: +33 1 61 69 30 92; Email: didier.smadja@chsf.fr
    • Principal Investigator: Nicolas CHAUSSON

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

This is a monocentric retrospective study (Sud-Francilien Hospital (SFH), Corbeil-Essonnes, France) based on a stroke registry prospectively gathered.

From March 2016 to February 2020, consecutive patients with acute ischemic stroke (AIS) assessed on brain MRI and treated with IVT alone who fulfilled the following criteria will be included: 18 years or older; evidence of an AIS on acute MRI (MRI-1) associated with a distal vessel occlusion as defined below; IVT within 4h30 of symptoms onset; availability of a post-IVT MRI within 1-2 hours (MRI-2); good quality of MRI sets including SWAN images.

Description

Inclusion Criteria:

• Age≥ 18 years.

• Acute ischemic stroke (visible on DWI, but not visible on FLAIR) on initial MRI associated with distal arterial occlusion as defined below:

  • A distal occlusion of the M2 segment of the middle cerebral artery (MCA)
  • Occlusion (regardless of location) of a non-dominant M2 branch of the MCA
  • Occlusion of the M3 segment of the MCA.
  • Occlusion of the A2 or A3 segment of the anterior cerebral artery (ACA)
  • Occlusion of the P2 or P3 branch of the posterior cerebral artery (PCA).
  • A proximal M2-MCA or proximal P1-PCA occlusion may also be included if not eligible for mechanical thrombectomy, especially if the initial NIHSS score is low (<5).
  • Distal arterial occlusion is identified by MRI either on the TOF (Time of Flight)-ARM sequence and/or on the presence of a thrombus (Susceptibility Vessel sign, SVS) on the SWAN sequence,
• IVT by ALT or TNK within 4H30 after onset of symptoms,
• Early brain MRI performed 1 to 2 hours after IVT (MRI n°2),
• Good quality MRI (absence of motion artifact interfering with interpretation) with availability of DWI, FLAIR, TOF-MRA and SWAN sequences.

Exclusion Criteria:

- Patients informed of the study who objected to the collection of their data.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Alteplase (ALT); Patients with distal vessel occlusion stroke treated with alteplase (from March 2016 to February 2018)	Drug: Alteplase (0.9mg/kg); Intravenous thrombolysis with Alteplase (0.9 mg/kg, maximum 90 mg) with 10% of the dose given as a bolus followed by an infusion lasting 60 minutes.
Tenecteplase (TNK); Patients with distal vessel occlusion stroke treated with tenecteplase (from March 2018 to February 2020)	Drug: Tenecteplase (0.25mg/kg); Intravenous thrombolysis with Tenecteplase (0.25mg/kg, maximum 25 mg) with 100% of the dose given as a bolus.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early successful recanalization rate	Early successful recanalization rate defined by an Arterial Occlusive Lesion (AOL) scale grade 2 or 3 on MRI-2 performed between 1 and 2 hours after IVT.	Between 1 and 2 hours after IVT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early complete recanalization rate	Early complete successful recanalization rate defined by an Arterial Occlusive Lesion (AOL) scale grade 3 on MRI-2 performed between 1 and 2 hours after IVT.	Between 1 and 2 hours after IVT
Thrombus length change	Thrombus length (TL) was approximated by measuring the susceptibility vessel sign (SVS) on the susceptibility weight angiography (SWAN) sequence. TL were measured in the 3 spatial planes, the higher value being retained. When thrombus persisted on MRI-2, TL reduction was assessed as follows : (MRI-1 length - MRI-2 length)/MRI-1 length X 100.	Between 1 and 2 hours after IVT
Evolution of cerebral infarct volume	Volume of the ischemic lesion will be assessed on the diffusion-weighted imaging (DWI) sequence using an automated software (Olea software). This evolution of cerebral infarct volume will be calculated as follows : DWI MRI volume n°2 - initial DWI MRI volume.	Between 1 and 2 hours after IVT
Rates of early post-thrombolysis intracerebral hemorrhage	Rates of early post-thrombolysis intracerebral hemorrhage on MRI-2 (performed at 1 to 2h after IVT) according to the Heidelberg classification (Kummer et al, Stroke 2015)	Between 1 and 2 hours after IVT
Very early clinical modification	Very early neurological modification was assessed as follows : baseline NIHSS -NIHSS at H1. Very early clinical improvement (VENI) was defined as baseline NIHSS -NIHSS at H1. ≥4, or NIHSS H1=0.	Between 1 and 2 hours after IVT

Collaborators and Investigators

• Sponsor: Centre Hospitalier Sud Francilien

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: November 23, 2022
• First Submitted That Met QC Criteria: November 23, 2022
• First Posted (Actual): December 2, 2022

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: thrombolysis; occlusion; tenecteplase; ischemic; alteplase; Acute; recanalization; stroke-distal
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Tenecteplase
• Other Study ID Numbers: 2022/0037

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