Phase 3
N=458
Tenecteplase in Stroke Patients Between 4.5 and 24 Hours
THROMBOLYSIS
Bottom Line
View on ClinicalTrials.gov: NCT03785678 ↗Enrolled (actual)
458
Serious AEs
44.7%
Results posted
May 2024
Primary outcome: Primary: Ordinal Modified Rankin Scale (mRS) Score at Day 90 — 35; 31; 38; 30 Count of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Tenecteplase (Biological); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Genentech, Inc.
- Primary completion
- Feb 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Ordinal Modified Rankin Scale (mRS) Score at Day 90 |
35; 31; 38; 30; 31; 36 | — |
| SECONDARY Proportion of Patients With Functional Independence at Day 90 |
46.0; 42.4; 54.0; 57.6 | — |
| SECONDARY Proportion of Patients With Recanalization at 24 Hours Post-randomization |
76.7; 63.9; 23.3; 36.1 | — |
| SECONDARY Proportion of Patients With Reperfusion at 24 Hours Post-randomization |
56.9; 57.7; 43.1; 42.3 | — |
| SECONDARY Proportion of Patients With Angiographic Reperfusion at Completion of Angiographic Procedure |
89.1; 85.4; 10.9; 14.6 | — |
| SECONDARY Median NIHSS Score at Day 90 |
1.0; 1.0 | — |
| SECONDARY Proportion of Patients With a Barthel Index (BI) Score ≥ 95 at Day 90 |
60.5; 58.4; 39.5; 41.6 | — |
| SECONDARY Proportion of Patients With Good Recovery Based on the Glasgow Outcome Scale (GOS) at Day 90 |
36.5; 30.8; 63.5; 69.2 | — |
| SECONDARY Incidence of Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours |
3.2; 2.3 | — |
| SECONDARY Mortality Rate up to Day 30 and Day 90 |
14.7; 15.0; 19.7; 18.2 | — |
| SECONDARY Proportion of Patients With Parenchymal Hematoma Type 2 (PH2) at the 72-96 Hour Visit |
3.7; 2.8 | — |
Summary
This study will evaluate the efficacy and safety of tenecteplase compared with placebo in participants with acute ischemic stroke (AIS).
All participants will receive standard-of-care therapy according to AmericanHeart Association/American Stroke Association clinical guidelines (2018). To determine eligibility for randomization, all participants will undergo multimodal CT or MRI at baseline. Only participants with a vessel occlusion (ICA or MCA M1/M2) and penumbral tissue will be randomized. The primary analysis is to compare the efficacy of tenecteplase versus placebo in all participants at Day 90.
Eligibility Criteria
Inclusion Criteria
- Patient/legally authorized representative has signed the Informed Consent Form
- Age >= 18 years
- AIS symptom onset within 4.5 to 24 hours Signs and symptoms consistent with the diagnosis of an acute anterior circulation ischemic stroke involving occlusion of the ICA, M1, or M2 vessels
- Functionally independent (mRS 0-2) prior to stroke onset
- Baseline NIHSS >=5 and that remains >=5 immediately prior to randomization
- Neuroimaging: ICA or M1, M2 occlusion (carotid occlusions can be cervical or intracranial, with or without tandem MCA lesions) by magnetic resonance angiography (MRA) or computed tomography angiography (CTA) AND target mismatch profile on CT perfusion or MR perfusion (ischemic core volume =1.8 and mismatch volume is >= 15 mL)
- The mismatch volume is determined by FDA-approved imaging software in real time based on the difference between the ischemic core lesion volume and the Tmax>6s lesion volume. If both a CT perfusion and a multimodal MRI scan are performed prior to enrollment, the later of the 2 scans is assessed to determine eligibility. Only an intracranial MRA is required for patients screened with MRA; cervical MRA is not required. Cervical and intracranial CTA are typically obtained simultaneously in patients screened with CTA, but only the intracranial CTA is required for enrollment.
Alternative neuroimaging:
- If CTA (or MRA) is technically inadequate: Tmax>6s perfusion deficit consistent with an ICA or M1, M2 occlusion AND target mismatch profile (ischemic core volume = 1.8 and mismatch volume >= 15 mL as determined by RAPID software)
- If magnetic resonance perfusion (MRP) is technically inadequate: ICA or M1, M2 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA (or CTA, if MRA is technically inadequate and a CTA was performed within 60 minutes prior to the MRI) AND diffusion-weighted imaging (DWI) lesion volume 1.7
- Use of one of the new oral anticoagulants within the last 48 hours (dabigatran, rivaroxaban, apixaban, edoxaban)
- Pregnant
- Intracranial neoplasm (except small meningioma), arteriovenous malformation, or aneurysm
- Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS
- Severe, uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure > 110 mmHg)
- For participants with suspected coagulopathy, platelet count must be checked prior to randomization and participant is excluded if baseline platelet count 400 mg/dL (22.20 mmol/L)
- Baseline blood glucose 1/3 MCA territory, or significant hypodensity outside the Tmax>6s perfusion lesion that invalidates mismatch criteria (if patient is enrolled based on CT perfusion criteria)
- Significant mass effect
- Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA/MRA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion)
- Evidence of intracranial tumor (except small meningioma) acute intracranial hemorrhage, neoplasm, or arteriovenous malformation
Data sourced from ClinicalTrials.gov (NCT03785678). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.