A Phase 1 interventional study of Tenecteplase (TNK) (0.25 mg/kg, to maximum of 25mg) in Acute Ischemic Stroke, sponsored by Memorial Hermann Health System. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2025-06-05.
Sponsored by Memorial Hermann Health System · Phase 1, Interventional, and Treatment
In this pilot safety study, the investigators will give a second dose of Intravenous Tenecteplase (IV TNK) to patients receiving the initial TNK dose within 3 hrs of last known normal (LKN), have a baseline National Institutes of Health Stroke Scale (NIHSS) > 6, and who do not clinically improve within 45 minutes of the first dose, or who improve but then deteriorate, and can still be treated within 4.5 hours from LKN. Patients will require a second computed tomography (CT) scan to rule out any bleeding, and meet the usual inclusion and exclusion criteria for TNK treatment, before the second dose which must be given within 4.5 hrs of LKN. Both TNK doses will be 0.25 mg/kg. The initial TNK dose may be given on the Mobile Stroke Unit (MSU) or Emergency Department (ED), and the second dose in the ED. Informed consent will be obtained before the second dose is given.
The primary outcome will be symptomatic intracranial hemorrhage (sICH) (SITS-MOST criteria) or serious systemic bleeding within 36 hours. Secondary outcomes will be any intracranial hemorrhage, any bleeding, discharge NIHSS and modified Rankin Score (mRS), and mRS at 90 days (sliding dichotomy).
20 patients will be enrolled. Enrollment will be stopped if more than 3 sICH occur (> 80% confidence that sICH rate is > 5%. If successful, this study will be followed by a larger phase 2b controlled safety confirmation and pilot efficacy study,
Background: Patients who are eligible for "IVT only" (IVT-O) represent the largest cohort of acute ischemic stroke (AIS) patients who are eligible for IVT, approximately three times larger than those who qualify for both IVT and endovascular thrombectomy (EVT). In all studies of IVT, at least 50% of patients remain disabled at 90 days, generating interest in finding treatments that might augment the beneficial effects of IVT, especially in the majority of AIS patients for whom EVT is not an option. The approved standard doses of tissue plasminogen activator (tPA) and TNK, while based on limited data, suggest that single doses above the approved 0.9 mg/kg of tPA and 0.25 mg/kg TNK will produce excessive bleeding. Another strategy might be to give a second dose of IVT. The relative short half-life of both tPA and TNK after completion of their infusion (5-25 minutes) mean that a second dose might be given while brain tissue is still in the penumbral state which may last for many hours following stroke onset depending on collateral flow. A recent study from France evaluated dual treatment in patients with documented medium vessel occlusion (MeVO) on magnetic resonance angiography (MRA) 1 hour after receiving a single dose of tPA (pts treated within 4.5 hrs of onset and no lesion on magnetic resonance imaging fluid inversion recovery (MRI FLAIR). At one hospital, 146 patients were identified, of whom 96 received TNK on average 116 minutes after tPA. These patients were compared by propensity matching to 148 patients receiving only tPA at another hospital. Dual dose patients showed higher rates of recanalization at 24 hrs (77% vs 61%), better outcome (mRS at 90 days), and no increased bleeding. These very encouraging results in patients limited to those with documented MeVO demonstrate the probable safety of dual IVT dosing and support its ability to increase recanalization in distal vessels thereby improving clinical outcome.
Another strategy would be to use clinical criteria (NIHSS) rather than relying on vascular imaging to identify patients qualifying for a second dose of IVT. The MOST study data demonstrate that 69% of patients with NIHSS > 6 who qualify for IVT and not EVT do not have clot identifiable on vascular imaging and therefore probably harbor more distal occlusions. Furthermore, obtaining a second vascular study 1 hour after the first dose of IVT is problematic at most clinical sites due to lack of availability for obtaining MRA and inability to use CTA due to excessive radiation and contrast. The NIHSS can also be used to identify and exclude those patients who respond to the first dose of IVT. Transcranial doppler studies have shown that early recanalization is associated with rapid clinical improvement on the NIHSS. If the first lytic dose were given within the approved 3 hours, a second dose could still be administered after most of the first dose is dissipated and still within the 4.5 hour time window in those patients who do not clinically improve after the first dose or who initially improve and then deteriorate.
Study Design: In this pilot safety study, the investigators will give a second dose of IV TNK to patients receiving the initial TNK dose within 3 hrs of LKN, have a baseline NIHSS > 6, and who do not clinically improve within 45 minutes of the first dose, or who improve but then deteriorate, and can still be treated within 4.5 hours from LKN. Patients will require a second CT scan to rule out any bleeding, and meet the usual inclusion and exclusion criteria for TNK treatment, before the second dose which must be given within 4.5 hrs of LKN. Both TNK doses will be 0.25 mg/kg. The initial TNK dose may be given on the MSU or ED, and the second dose in the ED. Informed consent will be obtained before the second dose is given.
The primary outcome will be symptomatic ICH (SITS-MOST criteria) or serious systemic bleeding within 36 hours. Secondary outcomes will be any intracranial hemorrhage, any bleeding, discharge NIHSS and mRS, and mRS at 90 days (sliding dichotomy).
20 patients will be enrolled. Enrollment will be stopped if more than 3 sICH occur (> 80% confidence that sICH rate is > 5%. If successful, this study will be followed by a larger phase 2b controlled safety confirmation and pilot efficacy study,
Inclusion criteria for both doses unless indicated otherwise:
Interventional sequence:
Repeat NIHSS 45 minutes post TNK bolus
o If repeat NIHSS still > 6, obtain repeat NCCT and review criteria for TNK
2,612 studies on the registry are indexed under Ischemic Stroke; 971 are open to participants now.
This study's planned enrollment of 20 is below the median of 120 across 1,776 interventional studies indexed under Ischemic Stroke.
Browse Ischemic Stroke studies →Memorial Hermann Health System is the lead sponsor of 8 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The investigators will give a second dose of IV TNK to patients receiving the initial TNK dose within 3 hrs of LKN, have a baseline NIHSS \> 6, and who do not clinically improve within 45 minutes of the first dose, or who improve but then deteriorate, and can still be treated within 4.5 hours from LKN. Patients will require a second CT scan to rule out any bleeding, and meet the usual inclusion and exclusion criteria for TNK treatment, before the second dose which must be given within 4.5 hrs of LKN. Both TNK doses will be 0.25 mg/kg. The initial TNK dose may be given on the MSU or ED, and the second dose in the ED.
Drug: Tenecteplase (TNK) (0.25 mg/kg, to maximum of 25mg)
Drug page: Tenecteplase
All patients will receive a second dose of tenecteplase.
The number of patients with symptomatic intracerebral hemorrhage or major systemic bleeding
A type 2 parenchymal hemorrhage or a parenchymal hemorrhage remote from the area of infarction with neurological deterioration (≥4-point worsening in National Institutes of Health Stroke Scale) and major hemorrhage (requiring \>2 units packed red blood cells)
Time frame: within 36 hours of enrollment (2nd dose of tenecteplase)
Clinical efficacy outcome
National Institutes of Health Stroke Scale (range 0-42 points with lower score indicating less severe stroke) and modified Rankin scale (range 0-6 with lower score indicating less disability)
Time frame: 90 days post stroke
Plan to share: Yes — De-identified clinical and outcome data
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: 1 year after study completion (start date), 5 years after study completion (end date)
Access criteria: Any academic investigator upon written request to the principal investigator
No publications or documents are linked to this record.
Start is estimated for Jul 2025; primary completion for Jun 2026, 11 months later.
Of 42 phase 1 interventional studies under Ischemic Stroke, half reached primary completion within 15 months of starting (the median), counting those still running; a quarter within 7 and three quarters within 29. This study's planned 11 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in May 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Tenecteplase
Memorial Hermann Health System