Safety and Efficacy of intra-arterial Tenecteplase for non-complete reperfusion of intracranial occlusion

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Insel Gruppe AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

23 Jan 2025 → ongoing

Decision date (initial)

2024-09-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Swiss National Science Foundation (SNF)

External identifiers

EU CT number

2022-502878-16-00

ClinicalTrials.gov

NCT05499832

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of this trial is to determine the safety and efficacy of intra-arterial Tenecteplase in patients experiencing an acute ischemic stroke due to a large vessel occlusion with incomplete reperfusion with residual occlusions after mechanical thrombectomy.

Secondary objectives 1

1. Secondary objectives include to evaluate if patients treated with additional intra-arterial Tenecteplase have superior outcome in terms of clinical efficacy and technical efficacy as opposed to the control group.

Conditions and MedDRA coding

Acute ischemic strokes with incomplete reperfusion

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Informed consent
2. Age ≥18 years
3. Clinical signs consistent with an acute ischemic stroke
4. Patient had an initial large vessel occlusion in the anterior circulation defined as intracranial ICA, M1, M2, M3, A1, A2, P1 or P2
5. Patient has undergone endovascular stroke treatment
6. Onset to randomization no later than < 705 minutes (11h 45min) after symptom-onset/last-seen well.
7. Incomplete reperfusion defined as any of the following: a. For ICA/M1: TICI2b/2c (50-99%) reperfusion after endovascular treatment without mechanically amendable target-occlusion (as per definition by the interventionalist). b. For A1/A2, P1/P2, M2/M3: TICI2a/2b/2c (1-99%) reperfusion after endovascular treatment without mechanically amendable target-occlusion (as per definition by the interventionalist). c. Any emboli to the new territory without mechanically amendable target-occlusion (as per definition by the interventionalist).
8. Signs of early ischemic changes of non-contrast CT Alberta Stroke Program Early CT Score (ASPECTS) ≥5 (for DWI-ASPECTS ≥ 4, for DWI-ASECTS: a region must have diffusion abnormality in 20% or more of its volume to be considered DWI-ASPECTS positive)

Exclusion criteria 20

1. Acute intracranial hemorrhage
2. Active dyspeptic ulcer
3. Known arterial aneurysm
4. Known neoplasms with risk of bleeding
5. Severe liver fibrosis or portal hypertension
6. Acute pericarditis
7. Acute pancreatitis
8. Known allergy to TNK or Gentamicin or other additives/auxiliaries (Polysorbatum 20, L-Argininum, Acidum phosphoricum)
9. Known Renal failure either as defined by a serum creatinine > 3.0 mg/dl (or 265.2 μmol/l) or glomerular Filtration Rate [GFR] < 30 or as subject who required hemodialysis/peritoneal dialysis
10. Radiological confirmed evidence of mass effect or intracranial tumor (except small meningioma)
11. Radiological confirmed evidence of cerebral vasculitis
12. Contraindication to MRI (e.g. pacemaker)
13. Pregnancy or lactating women
14. Any severe bleeding within the past 6 months, which would prevent administration of intravenous thrombolysis in clinical routine
15. Major surgery in the past 2 months with severe risk of bleeding which would prevent administration of intravenous thrombolysis in clinical routine
16. Intake of Vitamin K antagonista with INR >1.7
17. Platelets < 50,000
18. Non-controlled hypertension (defined as SBP >185 mmHg or DBP >110 mmHg refractory to treatment)
19. Calcified thrombi
20. Acute endocarditis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Early and late reperfusion

Secondary endpoints 6

1. Degree of disability or dependence at 90+/-15 days as assessed by the mRS (shift analysis)
2. Normalized change in NIHSS at 24+/- 6h post-randomization.
3. Change in NIHSS at 90+/- 15 days post-randomization.
4. Quality of life as assessed by the EuroQol 5D-3L at 90+/- 15 days
5. All-cause mortality at 90 days
6. No significant disability (i.e. mRS 0-1) at 90+/-15 days

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Insel Gruppe AG

Sponsor organisation

Insel Gruppe AG

Address

Freiburgstrasse 18

City

Bern

Postcode

3010

Country

Switzerland

Scientific contact point

Organisation

Insel Gruppe AG

Contact name

Johannes Kaesmacher

Public contact point

Organisation

Insel Gruppe AG

Contact name

Johannes Kaesmacher

Locations

6 EU/EEA countries · 47 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 68 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

15 submissions — initial application plus substantial / non-substantial modifications