Acute Ischemic StrokePhase 3NCT06749834
Intravenous Thrombolysis and NOAC
A Phase 3 study testing Intravenous thrombolysis in people with Acute Ischemic Stroke, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 2 sites in China.
Trial summary
New oral anticoagulants (NOACs), including rivaroxaban, apixaban, dabigatran, and edoxaban, have become the first-line therapy for preventing ischemic stroke associated with non-valvular atrial fibrillation (NVAF). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Ischemic Stroke
- What is being tested?
- Intravenous thrombolysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 2 sitesChina
- Study dates
- 27 Jan 2025to 30 Jun 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with clinical signs of acute ischemic stroke within 24 hours of onset or awakening with stroke (if within 24 hours from the midpoint of sleep). Patients with AIS within 4.5-24 hours of onset must meet the IVT inclusion criteria specified in the guideline
- Patients with new oral anticoagulants usage within 4-48 hours of onset;
- Patients ≥ 18 years old
- Informed consent has been obtained depending on local ethics requirements.
Who cannot join
- Intended to proceed to endovascular treatment
- With APTT >40s
- Pre-stroke mRS score > 2
- Contraindications for IVT：
- 1) Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, epidural hematoma, etc.) 2) Previous history of intracranial hemorrhage 3) Severe head trauma or stroke history within the last 3 months 4) Intracranial tumors, giant intracranial aneurysms 5) Intracranial or spinal surgery within the recent 3 months 6) Major surgical procedures within the last 2 weeks 7) Gastrointestinal or urinary tract bleeding within the last 3 weeks 8) Active visceral bleeding 9) Aortic arch dissection 10) Arterial puncture in a site within the last 1 week that is not easy to compress and stop bleeding 11) Elevated blood pressure: Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg 12) Acute bleeding tendency, including platelet count < 100 × 10⁹/L or other conditions 13) Received low-molecular-weight heparin treatment within 24 hours 14) Oral anticoagulants (warfarin) with INR > 1.7 or PT > 15 s 15) Blood sugar < 2.8 or > 22.22 mmol/L 16) Head CT or MRI indicates large-area infarction (infarction area ≥ 1/3 of the middle cerebral artery supply area) (4) The judgment is left to the discretion of the investigator
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Not yet recruiting
Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou
Hangzhou, Zhejiang, 310000
Min Lou, PhD, MD, 8613958007213, lm99@zju.edu.cn
Wansi Zhong, MD, 8618757155806, 21718233@zju.edu.cn
- Recruiting
The First People's Hospital of Wenling
Taizhou, Zhejiang, 317500
Hinlong Huo, 8615958755756, jaydenhuo@163.com
About this study
Official title: Intravenous Thrombolytic Therapy in Acute Ischemic Stroke Patients on New Oral Anticoagulants
New oral anticoagulants (NOACs), including rivaroxaban, apixaban, dabigatran, and edoxaban, have become the first-line therapy for preventing ischemic stroke associated with non-valvular atrial fibrillation (NVAF). Despite the effectiveness of NOACs in preventing thromboembolic events, approximately 1% to 2% of patients taking NOACs experience an ischemic stroke annually. Intravenous thrombolysis is an important means of treating acute ischemic stroke (AIS). However, due to concerns about the risk of symptomatic intracranial hemorrhage (sICH) or other severe bleeding complications, current guidelines still consider the use of NOACs within 48 hours before symptom onset as a contraindication to intravenous thrombolysis. Epidemiological data suggest that this may result in up to 18% of AF patients being unable to receive intravenous thrombolysis when they have an AIS episode.
Previous animal experiments have shown that NOACs do not increase the risk of hemorrhagic transformation after intravenous thrombolysis. Pharmacokinetic studies have demonstrated that 24 to 48 hours after taking NOACs, the anti-Xa level in patients is relatively low (<0.5 U/mL). In recent years, multiple retrospective studies and meta-analyses have shown that prior use of NOACs does not increase the risk of sICH in AIS patients receiving intravenous thrombolysis, and there are no significant differences in functional outcomes at 3 months. With solid pharmacokinetic and retrospective clinical evidence to support, it is hypothesized that IVT are safe in IS-NOAC patient. The investigators hereby propose a prospective multicenter study to determine the efficacy and safety of IVT in acute IS-NOAC.
Read the detailed description
In this prospective cohort study, the investigators aim to recruit consecutive IS-NOAC patients who met the inclusion criteria. The investigators sought to determine the safety and efficacy of IVT in acute ischemic stroke patients on NOACs. It is hypothesized that for IS-DOAC patients with the last intake of NOAC within 48 hours, IVT improved neurological outcomes with acceptable safety compared to a cohort of acute IS-NOAC patients excluded from IVT.
- Conditions
- Acute Ischemic Stroke
- Being tested
- Intravenous thrombolysis
- Keywords
- Intravenous thrombolysis, outcome, NOAC
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous thrombolysisDrug
Patients will receive standard dose intravenous alteplase (0.9 mg/kg, the first 10% administered as an initial bolus and the remainder over a 1-hour period, with a maximum dose of 90 mg)，intravenous Tenecteplase(0.25mg/kg，administered as a single intravenous bolus injection over 5 - 10 seconds，with a maximum dose of 25 mg), intravenous reteplase (a bolus of 18 mg followed by a second bolus of 18 mg after 30 minutes) and intravenous prourokinase (rhPro-UK) (15 mg bolus followed by a 20 mg infusion over 30 minutes).
| Study group | Role | What they receive |
|---|---|---|
| Intravenous thrombolysis | Experimental | Patients will receive standard dose intravenous alteplase (0.9 mg/kg, the first 10% administered as an initial bolus and the remainder over a 1-hour period, with a maximum dose of 90 mg)，intravenous Tenecteplase(0.25mg/kg，administered as a single intravenous bolus injection over 5 - 10 seconds，with a maximum dose of 25 mg), intravenous reteplase (a bolus of 18 mg followed by a second bolus of 18 mg after 30 minutes) and intravenous prourokinase (rhPro-UK) (15 mg bolus followed by a 20 mg infusion over 30 minutes). Receives: Drug: Intravenous thrombolysis |
| Standard therapy | No intervention | Standard therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Excellent recovery assessed by the ratio of modified Rankin Scale (mRS) score of 0-1 (%) at 90 ± 7 days
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
Measured: 90 ± 7 days
Secondary outcomes (7)
the change on the National Institute of Health stroke scale (NIHSS) score from baseline to 1 day
NIHSS: minimum value = 0, maximum value = 42, and higher scores mean severer symptoms
Measured: from baseline to 1 day
Independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%) at 90 ± 7 days
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
Measured: 90 ± 7 days
recovery assessed by modefied Rankin Scale (mRS) score
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
Measured: 90 ± 7 days
3-month mortality
Hospitalization records or follow-up results
Measured: 90 ± 7 days
Presence of parenchymal hemorrhage (PH)
the presence of PH is defined according the standard from ECASS-2 study
Measured: at day 1
Presence of symptomatic intracerebral hemorrhage (sICH)
the presence of sICH is defined according the standard from ECASS-2 study
Measured: at day 1
Presence of hemorrhagic transformation
Presence of hemorrhagic transformation is defined according the standard from ECASS-2 study
Measured: at day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2024
- Study start27 Jan 2025
- Primary completion31 Dec 2026 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06749834
- Sponsor's protocol ID
- I-NOAC
- Status last verified
- Dec 2024
- First submitted
- 15 Dec 2024
- Last updated
- 24 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Protecting the privacy of participants is a priority, and sharing IPD could potentially compromise this.
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravenous Thrombolytic Therapy in Acute Ischemic Stroke Patients on New Oral Anticoagulants
- ClinicalTrials.gov ID
- NCT06749834
- Acronym / sponsor ID
- I-NOAC
- Conditions
- Acute Ischemic Stroke
- Keywords
- Intravenous thrombolysis, outcome, NOAC
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 27 Jan 2025 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 27 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
New oral anticoagulants (NOACs), including rivaroxaban, apixaban, dabigatran, and edoxaban, have become the first-line therapy for preventing ischemic stroke associated with non-valvular atrial fibrillation (NVAF). Despite the effectiveness of NOACs in preventing thromboembolic events, approximately 1% to 2% of patients taking NOACs experience an ischemic stroke annually. Intravenous thrombolysis is an important means of treating acute ischemic stroke (AIS). However, due to concerns about the risk of symptomatic intracranial hemorrhage (sICH) or other severe bleeding complications, current guidelines still consider the use of NOACs within 48 hours before symptom onset as a contraindication to intravenous thrombolysis. Epidemiological data suggest that this may result in up to 18% of AF patients being unable to receive intravenous thrombolysis when they have an AIS episode.
Previous animal experiments have shown that NOACs do not increase the risk of hemorrhagic transformation after intravenous thrombolysis. Pharmacokinetic studies have demonstrated that 24 to 48 hours after taking NOACs, the anti-Xa level in patients is relatively low (<0.5 U/mL). In recent years, multiple retrospective studies and meta-analyses have shown that prior use of NOACs does not increase the risk of sICH in AIS patients receiving intravenous thrombolysis, and there are no significant differences in functional outcomes at 3 months. With solid pharmacokinetic and retrospective clinical evidence to support, it is hypothesized that IVT are safe in IS-NOAC patient. The investigators hereby propose a prospective multicenter study to determine the efficacy and safety of IVT in acute IS-NOAC.
Detailed description
In this prospective cohort study, the investigators aim to recruit consecutive IS-NOAC patients who met the inclusion criteria. The investigators sought to determine the safety and efficacy of IVT in acute ischemic stroke patients on NOACs. It is hypothesized that for IS-DOAC patients with the last intake of NOAC within 48 hours, IVT improved neurological outcomes with acceptable safety compared to a cohort of acute IS-NOAC patients excluded from IVT.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous thrombolysis | Experimental | Drug: Intravenous thrombolysisPatients will receive standard dose intravenous alteplase (0.9 mg/kg, the first 10% administered as an initial bolus and the remainder over a 1-hour period, with a maximum dose of 90 mg)，intravenous Tenecteplase(0.25mg/kg，administered as a single intravenous bolus injection over 5 - 10 seconds，with a maximum dose of 25 mg), intravenous reteplase (a bolus of 18 mg followed by a second bolus of 18 mg after 30 minutes) and intravenous prourokinase (rhPro-UK) (15 mg bolus followed by a 20 mg infusion over 30 minutes). |
| Standard therapy | No intervention | –Standard therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with clinical signs of acute ischemic stroke within 24 hours of onset or awakening with stroke (if within 24 hours from the midpoint of sleep). Patients with AIS within 4.5-24 hours of onset must meet the IVT inclusion criteria specified in the guideline
- Patients with new oral anticoagulants usage within 4-48 hours of onset;
- Patients ≥ 18 years old
- Informed consent has been obtained depending on local ethics requirements.
Key exclusion criteria (5 listed)
- Intended to proceed to endovascular treatment
- With APTT >40s
- Pre-stroke mRS score > 2
- Contraindications for IVT：
- 1) Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, epidural hematoma, etc.) 2) Previous history of intracranial hemorrhage 3) Severe head trauma or stroke history within the last 3 months 4) Intracranial tumors, giant intracranial aneurysms 5) Intracranial or spinal surgery within the recent 3 months 6) Major surgical procedures within the last 2 weeks 7) Gastrointestinal or urinary tract bleeding within the last 3 weeks 8) Active visceral bleeding 9) Aortic arch dissection 10) Arterial puncture in a site within the last 1 week that is not easy to compress and stop bleeding 11) Elevated blood pressure: Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg 12) Acute bleeding tendency, including platelet count < 100 × 10⁹/L or other conditions 13) Received low-molecular-weight heparin treatment within 24 hours 14) Oral anticoagulants (warfarin) with INR > 1.7 or PT > 15 s 15) Blood sugar < 2.8 or > 22.22 mmol/L 16) Head CT or MRI indicates large-area infarction (infarction area ≥ 1/3 of the middle cerebral artery supply area) (4) The judgment is left to the discretion of the investigator
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous thrombolysisPatients will receive standard dose intravenous alteplase (0.9 mg/kg, the first 10% administered as an initial bolus and the remainder over a 1-hour period, with a maximum dose of 90 mg)，intravenous Tenecteplase(0.25mg/kg，administered as a single intravenous bolus injection over 5 - 10 seconds，with a maximum dose of 25 mg), intravenous reteplase (a bolus of 18 mg followed by a second bolus of 18 mg after 30 minutes) and intravenous prourokinase (rhPro-UK) (15 mg bolus followed by a 20 mg infusion over 30 minutes). | Drug | Intravenous thrombolysis |
Primary outcome
Excellent recovery assessed by the ratio of modified Rankin Scale (mRS) score of 0-1 (%) at 90 ± 7 days
Time frame: 90 ± 7 days
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
7 secondary outcomes
the change on the National Institute of Health stroke scale (NIHSS) score from baseline to 1 day
Time frame: from baseline to 1 day
Independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%) at 90 ± 7 days
Time frame: 90 ± 7 days
recovery assessed by modefied Rankin Scale (mRS) score
Time frame: 90 ± 7 days
3-month mortality
Time frame: 90 ± 7 days
Presence of parenchymal hemorrhage (PH)
Time frame: at day 1
Presence of symptomatic intracerebral hemorrhage (sICH)
Time frame: at day 1
Presence of hemorrhagic transformation
Time frame: at day 1
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
- Individual participant dataSharing planned: No. Protecting the privacy of participants is a priority, and sharing IPD could potentially compromise this.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intravenous thrombolysis in people with Acute Ischemic Stroke, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Min Lou, PhD, MD (8613958007213, lm99@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Excellent recovery assessed by the ratio of modified Rankin Scale (mRS) score of 0-1 (%) at 90 ± 7 days (time frame: 90 ± 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2025.