NCT05809921

Brief Summary

The purpose of this study (Dual IV thrombolysis Approach (DIVA) study) is to assess a new medical strategy for Medium-vessel-occlusion (MeVO) strokes, based on a second IV thrombolysis with tenecteplase (TNK) for persistent intracranial occlusion on MRI 1-2 hours after standard alteplase infusion. The DIVA-study results were compared with a similar cohort of MeVO strokes patients treated with standard therapy (single IVT with alteplase) during the same timeframe in another stroke unit.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
294

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started May 2023

Shorter than P25 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 30, 2023

Completed
13 days until next milestone

First Posted

Study publicly available on registry

April 12, 2023

Completed
1 month until next milestone

Study Start

First participant enrolled

May 17, 2023

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 13, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 13, 2023

Completed
Last Updated

November 7, 2023

Status Verified

November 1, 2023

Enrollment Period

4 months

First QC Date

March 30, 2023

Last Update Submit

November 3, 2023

Conditions

Acute Ischemic Stroke Due to Medium-vessel-occlusion

Keywords

Acute strokeMedium-vessel occlusionThrombolysisTenecteplase

Outcome Measures

Primary Outcomes (1)

  • Recanalization rate assed on the control MRI at 24h (MRI-3) based on the Arterial Occlusive Lesion (AOL) score

    Recanalization rate at 24h was evaluated on MRI-3 using the AOL scale. This scale was adapted for very distal occlusions which are not always clearly visible on magnetic resonance angiography (MRA). In these cases, AOL scale-score was based on gradient echo-sequences (GE): If occlusion visible on MRI: * no recanalization: AOL- 0, 1, 2a * successful recanalization : AOL-2b or 3 If occlusion not visible on MRA but thrombus visible on GE: * no recanalization : AOL-0 (unchanged thrombus) or AOL-1/AOL-2a (slight down-stream migration ore size reduction of the thrombus) * successful recanalization : AOL-2b (residual distal thrombus), or AOL-3 (complete thrombus disappearance).

    at 24 hours

Secondary Outcomes (4)

  • Symptomatic intracranial Hemorrhages (sICH)

    at 24 hours

  • NIHSS

    at 24 hours

  • modified Rankin Scale score (mRS)

    at 3 months

  • mRS 6

    at 3 months

Study Arms (2)

Single-IVT strategy (SIS) cohort

The SIS cohort included patients with MeVO strokes who received a single conventional alteplase IVT (IVT-1).

Drug: alteplase

Dual-IVT strategy (DIS) cohort

The DIS cohort included patients with alteplase-treated MeVO strokes for whom a repeat MRI (MRI-2) was planned 1-2h after alteplase IVT (IVT-1) to discuss a possible complementary IVT with tenecteplase (TNK-IVT-2). Patients could be in the following situations: already recanalized at 1-2h post-alteplase IVT-1, persistent occlusion treated with TNK-IVT-2 or persistent occlusion but additional IVT contraindicated according to the study protocol.

Drug: Alteplase + possible complementary IVT with tenecteplase

Interventions

alteplaseDRUG

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.

Single-IVT strategy (SIS) cohort
Alteplase + possible complementary IVT with tenecteplaseDRUG

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) and depending on the MRI-2 results, an additional IVT with tenecteplase (0.25mg/kg, maximum 25 mg, with 100% of the dose given as a bolus) could be given in case of persistent occlusion and with no contraindication according to the study protocol.

Dual-IVT strategy (DIS) cohort

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

This is a bicentric retrospective study: Sud-Francilien Hospital (SFH), Corbeil-Essonnes, France for the DIVA cohort and Bordeaux University Hospital (BUH) for the standard treatment with alteplase alone cohort, based on stroke registries prospectively gathered. From March 2014 to November 2018, consecutive patients in SFH and BUH with acute ischemic stroke (AIS) due to distal occlusion assessed on brain MRI who fulfilled the inclusion/exclusion criteria were included in this retrospective analysis.

You may qualify if:

  • For the SIS cohort :
  • 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).
  • IVT by ALT within 4h30 after onset of symptoms,
  • MRI performed 24h after IVT
  • For the DIS cohort :
  • Age≥ 18 years
  • Acute ischemic stroke (visible on DWI, but not visible on FLAIR) on baseline MRI associated with distal arterial occlusion as defined below:
  • A distal occlusion of the M2 segment of the middle cerebral artery (MCA)
  • +8 more criteria

You may not qualify if:

  • For the SIS cohort :
  • 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).
  • IVT by ALT within 4h30 after onset of symptoms,
  • MRI performed 24h after IVT
  • For the DIS cohort :
  • Age≥ 18 years
  • Acute ischemic stroke (visible on DWI, but not visible on FLAIR) on baseline MRI associated with distal arterial occlusion as defined below:
  • A distal occlusion of the M2 segment of the middle cerebral artery (MCA)
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Centre Hospitalier Sud Francilien

Corbeil-Essonnes, 91109, France

Location

Related Publications (1)

  • Chausson N, Olindo S, Laborne FX, Aghasaryan M, Renou P, Soumah D, Debruxelles S, Altarcha T, Poli M, L'Hermitte Y, Sagnier S, Toudou-Daouda M, Aminou-Tassiou NR, Bentamra L, Benmoussa N, Alecu C, Imbernon C, Smadja L, Ouanounou G, Rouanet F, Sibon I, Smadja D. Second-dose intravenous thrombolysis with tenecteplase in alteplase-resistant medium-vessel-occlusion strokes: A retrospective and comparative study. Eur Stroke J. 2024 Dec;9(4):943-951. doi: 10.1177/23969873241254936. Epub 2024 Jun 3.

    PMID: 38829011DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Tissue Plasminogen ActivatorTenecteplase

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine EndopeptidasesEndopeptidasesPeptide HydrolasesHydrolasesEnzymesEnzymes and CoenzymesSerine ProteasesPlasminogen ActivatorsBlood Coagulation FactorsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsBiological Factors

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
RETROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 30, 2023

First Posted

April 12, 2023

Study Start

May 17, 2023

Primary Completion

September 13, 2023

Study Completion

September 13, 2023

Last Updated

November 7, 2023

Record last verified: 2023-11

Data Sharing

IPD Sharing
Will not share

Locations

FR(1)