StrokePhase 3NCT04879615
24 Hours Treatment with Alteplase in Patients with Ischemic Stroke
A Phase 3 study testing Alteplase in people with Stroke, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 26 sites in China.
Trial summary
The development of intravenous thrombolysis has greatly improved the rate of recanalization and reperfusion in patients with acute ischemic stroke, increasing the proportion of patients with good outcome and reduced mortality. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- Alteplase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 372 participants
- Where
- 26 sitesChina
- Study dates
- 21 Jun 2021to 30 Sep 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 presenting with clinical signs of acute ischemic stroke between 4.5 and 24 hours from stroke onset, or awakening and unwitnessed stroke (if the midpoint of the last known well time is within 4.5 to 24 hours)
- Patients aged > 18 years
- NIHSS range from 4 to 26
- Imaging inclusion criteria: ischemic core volume ≤ 70 mL, penumbra ≥ 10 mL and mismatch ≥ 20% (as evaluated by CT-perfusion)
- Pre-stroke mRS score < 2
- Informed consent has been obtained from the patient, a family member, or a legally responsible person, depending on local ethics requirements
Who cannot join
- Intended to proceed to endovascular treatment
- Contraindications for alteplase:
- Allergy to alteplase
- Rapidly improving symptoms at the discretion of the investigator
- The presence of epileptic seizures, hemiplegia after seizures (Todd's palsy), or other neurological/mental illness that prevents cooperation or willingness to participate
- Persistent blood pressure elevation (systolic ≥180 mmHg or diastolic ≥100 mmHg) despite treatment
Show all 18Show fewer
- Blood glucose levels outside the acceptable range (<2.8 or >22.2 mmol/L, point-of-care glucose testing accepted)
- High risk of bleeding due to active internal bleeding, major surgery, trauma, gastrointestinal, or urinary tract hemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days
- Known impairments in coagulation due to comorbid disease or anticoagulant use, including an INR >1.7 or prothrombin time >15 seconds for those on warfarin, recent use of direct thrombin inhibitors or direct factor Xa inhibitors without reversal capability, or full-dose heparin/heparinoid within the last 24 hours with an aPTT above normal limits
- Known defect in platelet function or a platelet count below 100,000/mm³
- History of ischemic stroke, myocardial infarction, intracranial hemorrhage, severe traumatic brain injury, or intraspinal operation within the previous 3 months, or known intracranial neoplasm, arteriovenous malformation, or giant aneurysm
- Acute or past intracerebral hemorrhage identified by CT or MRI
- Large (more than one-third of the territory of middle cerebral artery) region of clear hypodensity on CT scan
- Pregnancy, nursing, or unwillingness to use effective contraceptive measures during the trial period
- Likelihood of non-adherence to the trial protocol or follow-up
- Any condition that, in the judgment of the investigator, could impose hazards if study therapy is initiated or affect patient participation in the study
- Participation in other interventional clinical trials within the previous three months
- Life expectancy of less than three months
Trial locations and contacts
26 sites in 1 country.
26 sites in 1 country
China26 sites
Chongqing University Jiangjin Hospital
Chongqing
Binjiang Campus of Second Affiliated Hospital of Zhejiang University, School of Medicine
Hangzhou
Bo Ao Campus of Second Affiliated Hospital of Zhejiang University, School of Medicine
Hangzhou
Second Affiliated Hospital of Zhejiang University, School of Medicine
Hangzhou
Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College)
Hangzhou
Huzhou Central Hospital
Huzhou
First Affiliated Hospital of Jiaxing University
Jiaxing
Second Affiliated Hospital of Jiaxing University
Jiaxing
The First People's Hospital of Jiashan
Jiaxing
The Forth Affiliated Hospital of Zhejiang University
Jinhua
Affiliated Hospital of West Anhui Health Vocational College
Liuan
Mianyang Hospital of TCM
Mianyang
The First People's Hospital of Mianyang (SiChuan Mianyang 404 Hospital)
Mianyang
Nanjing Lishui District Hospital of Traditional Chinese Medicine
Nanjing
Ningbo No. 2 Hospital
Ningbo
Zhongshan Hospital
Shanghai
Shaoxing People's Hospital (Shaoxing Hospital of Zhejiang University)
Shaoxing
Suzhou Hospital of Anhui Medical University
Suzhou
The First Affiliated Hospital of Soochow University
Suzhou
Taizhou First People's Hospital
Taizhou
The First People's Hospital of Wenling
Taizhou
First Affiliated Hospital of Wenzhou Medical University
Wenzhou
Wuwei People's Hospital
Wuwei, Gansu
Zhangzhou Municipal Hospital of Fujian Province
Zhangzhou
The People's Hospital of Danyang
Zhenjiang
Zhongshan City People's Hospital
Zhongshan
About this study
Official title: Treatment with Intravenous Alteplase in Ischemic Stroke Patients with Onset Time Between 4.5 and 24 Hours
The development of intravenous thrombolysis has greatly improved the rate of recanalization and reperfusion in patients with acute ischemic stroke, increasing the proportion of patients with good outcome and reduced mortality. The guideline recommends that patients with ischemic stroke should be treated with intravenous thrombolysis within 4.5 hours. The latest meta-analysis found that ischemic stroke with onset time of 4.5-9 hours with infarction core volume <70ml, ischemic penumbra volume >10ml, and hypoperfusion volume / infarction core volume >1.2 could be benefit from intravenous thrombolysis. The DAWN clinical trial has shown that patients with ischemic stroke with large vessel occlusion with onset time of 6-24 hours could be benefit from endovascular treatment after screening by multi-mode imaging. Therefore, we hypothesize that patients with ischemic stroke with onset time of 4.5-24 hours with a definite penumbra may also benefit from intravenous thrombolysis. The purpose of this study is to explore whether the patients with ischemic stroke with onset time of 4.5-24 hours can benefit from intravenous thrombolysis if they meet the standard of CT perfusion screening.
Read the detailed description
In recent years, the development of intravenous thrombolysis has greatly improved the rate of recanalization and reperfusion in patients with acute ischemic stroke, increasing the proportion of patients with good outcome and reduced mortality. The guideline recommends that patients with ischemic stroke should be treated with intravenous thrombolysis within 4.5 hours. The latest meta-analysis found that ischemic stroke with onset time of 4.5-9 hours with infarction core volume <70ml, ischemic penumbra volume >10ml, and hypoperfusion volume / infarction core volume >1.2 could be benefit from intravenous thrombolysis (the ratio of mRS 0-1 in 3 months, thrombolysis vs non thrombolysis: 35.4% vs 29.5%). Thus, the time window is not an absolute constant indicator. In theory, compared with time window, the physiological window based on the concept of ischemic penumbra is more reasonable.
In 2015, the AHA/ASA guidelines recommended that patients with ischemic stroke with large vessel occlusion should receive endovascular treatment within 6 hours. The DAWN clinical trial has shown that patients with ischemic stroke with large vessel occlusion with onset time of 6-24 hours could be benefit from endovascular treatment after screening by multi-mode imaging (CT perfusion or MR perfusion). As a result, the 2018 AHA/ASA guidelines extended the endovascular treatment window to 24 hours for patients with large vessel occlusion stroke that meet the standard of perfusion. Therefore, we hypothesize that patients with ischemic stroke with onset time of 4.5-24 hours with a definite penumbra may also benefit from intravenous thrombolysis.
Thus, the purpose of this study is to explore whether the patients with ischemic stroke with onset time of 4.5-24 hours can benefit from intravenous thrombolysis if they meet the standard of CT perfusion screening (infarction core volume <70ml, ischemic penumbra volume >10ml, and hypoperfusion volume / infarction core volume >1.2).
- Conditions
- Stroke
- Being tested
- Alteplase
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlteplaseDrug
Patients will receive standard dose intravenous alteplase (0.9 mg per kilogram, the first 10% administered as an initial bolus and the remainder over a 1-hour period, with a maximum dose of 90 mg)
| Study group | Role | What they receive |
|---|---|---|
| Alteplase with standard therapy | Experimental | Not described Receives: Drug: Alteplase |
| Standard therapy | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Excellent recovery assessed by the ratio of modefied Rankin Scale (mRS) score of 0-1 (%)
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
Measured: at 90 days
Secondary outcomes (8)
Independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%)
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
Measured: at 90 days
Ratio of modefied Rankin Scale (mRS) score of 0-3 (%)
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
Measured: at 90 days
Ordinal distribution of mRS score
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
Measured: at 90 days
Major neurologic improvement defined as an improvement of ≥8 points on the NIHSS compared with the initial deficit or a score of ≤1 achieved (%)
NIHSS: minimum value = 0, maximum value = 42, and higher scores mean severer symptoms
Measured: at 24 hours
Major neurologic improvement defined as an improvement of ≥8 points on the NIHSS compared with the initial deficit or a score of ≤1 achieved (%)
NIHSS: minimum value = 0, maximum value = 42, and higher scores mean severer symptoms
Measured: at 7 days
Symptomatic intracerebral hemorrhage (sICH) (%)
sICH as defined by The European Cooperative Acute Stroke Study III criteria [ECASSIII]
Measured: within 36 hours
Parenchymal hematoma (PH) (%)
PH as defined by the European Cooperative Acute Stroke Study [ECASS] criteria
Measured: within 36 hours
Mortality (%)
mortality refers to rate of death from any cause
Measured: within 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2021
- Study start21 Jun 2021
- Primary completion30 Jun 2024
- Study completion30 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 372 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04879615
- Sponsor's protocol ID
- HOPE
- Status last verified
- Sep 2024
- First submitted
- 6 May 2021
- Last updated
- 5 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zhou Y, He Y, Campbell BCV, Liebeskind DS, Yuan C, Chen H, Zhang Y, Yi T, Luo Z, Zhang Z, Meng C, Cheng J, Ouyang H, Hu J, Wang F, Zhang S, Fang Q, Hu H, Zhang X, Chen Y, Zhong W, Lansberg MG, Yan S, Lou M; HOPE investigators. Alteplase for Acute Ischemic Stroke at 4.5 to 24 Hours: The HOPE Randomized Clinical Trial. JAMA. 2025 Sep 2;334(9):788-797. doi: 10.1001/jama.2025.12063.
PubMed 40773205
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment with Intravenous Alteplase in Ischemic Stroke Patients with Onset Time Between 4.5 and 24 Hours
- ClinicalTrials.gov ID
- NCT04879615
- Acronym / sponsor ID
- HOPE
- Conditions
- Stroke
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 372 participants (actual)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 21 Jun 2021 (actual)
- Primary completion
- 30 Jun 2024 (actual)
- Study completion
- 30 Sep 2024 (actual)
- First posted
- 10 May 2021 (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.
The development of intravenous thrombolysis has greatly improved the rate of recanalization and reperfusion in patients with acute ischemic stroke, increasing the proportion of patients with good outcome and reduced mortality. The guideline recommends that patients with ischemic stroke should be treated with intravenous thrombolysis within 4.5 hours. The latest meta-analysis found that ischemic stroke with onset time of 4.5-9 hours with infarction core volume <70ml, ischemic penumbra volume >10ml, and hypoperfusion volume / infarction core volume >1.2 could be benefit from intravenous thrombolysis. The DAWN clinical trial has shown that patients with ischemic stroke with large vessel occlusion with onset time of 6-24 hours could be benefit from endovascular treatment after screening by multi-mode imaging. Therefore, we hypothesize that patients with ischemic stroke with onset time of 4.5-24 hours with a definite penumbra may also benefit from intravenous thrombolysis. The purpose of this study is to explore whether the patients with ischemic stroke with onset time of 4.5-24 hours can benefit from intravenous thrombolysis if they meet the standard of CT perfusion screening.
Detailed description
In recent years, the development of intravenous thrombolysis has greatly improved the rate of recanalization and reperfusion in patients with acute ischemic stroke, increasing the proportion of patients with good outcome and reduced mortality. The guideline recommends that patients with ischemic stroke should be treated with intravenous thrombolysis within 4.5 hours. The latest meta-analysis found that ischemic stroke with onset time of 4.5-9 hours with infarction core volume <70ml, ischemic penumbra volume >10ml, and hypoperfusion volume / infarction core volume >1.2 could be benefit from intravenous thrombolysis (the ratio of mRS 0-1 in 3 months, thrombolysis vs non thrombolysis: 35.4% vs 29.5%). Thus, the time window is not an absolute constant indicator. In theory, compared with time window, the physiological window based on the concept of ischemic penumbra is more reasonable.
In 2015, the AHA/ASA guidelines recommended that patients with ischemic stroke with large vessel occlusion should receive endovascular treatment within 6 hours. The DAWN clinical trial has shown that patients with ischemic stroke with large vessel occlusion with onset time of 6-24 hours could be benefit from endovascular treatment after screening by multi-mode imaging (CT perfusion or MR perfusion). As a result, the 2018 AHA/ASA guidelines extended the endovascular treatment window to 24 hours for patients with large vessel occlusion stroke that meet the standard of perfusion. Therefore, we hypothesize that patients with ischemic stroke with onset time of 4.5-24 hours with a definite penumbra may also benefit from intravenous thrombolysis.
Thus, the purpose of this study is to explore whether the patients with ischemic stroke with onset time of 4.5-24 hours can benefit from intravenous thrombolysis if they meet the standard of CT perfusion screening (infarction core volume <70ml, ischemic penumbra volume >10ml, and hypoperfusion volume / infarction core volume >1.2).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alteplase with standard therapy | Experimental | Drug: Alteplase |
| Standard therapy | No intervention | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients presenting with clinical signs of acute ischemic stroke between 4.5 and 24 hours from stroke onset, or awakening and unwitnessed stroke (if the midpoint of the last known well time is within 4.5 to 24 hours)
- Patients aged > 18 years
- NIHSS range from 4 to 26
- Imaging inclusion criteria: ischemic core volume ≤ 70 mL, penumbra ≥ 10 mL and mismatch ≥ 20% (as evaluated by CT-perfusion)
- Pre-stroke mRS score < 2
Key exclusion criteria (18 listed)
- Intended to proceed to endovascular treatment
- Contraindications for alteplase:
- Large (more than one-third of the territory of middle cerebral artery) region of clear hypodensity on CT scan
- Pregnancy, nursing, or unwillingness to use effective contraceptive measures during the trial period
- Likelihood of non-adherence to the trial protocol or follow-up
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 |
|---|---|---|
| AlteplasePatients will receive standard dose intravenous alteplase (0.9 mg per kilogram, the first 10% administered as an initial bolus and the remainder over a 1-hour period, with a maximum dose of 90 mg) | Drug | Alteplase with standard therapy |
Primary outcome
Excellent recovery assessed by the ratio of modefied Rankin Scale (mRS) score of 0-1 (%)
Time frame: at 90 days
mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
8 secondary outcomes
Independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%)
Time frame: at 90 days
Ratio of modefied Rankin Scale (mRS) score of 0-3 (%)
Time frame: at 90 days
Ordinal distribution of mRS score
Time frame: at 90 days
Major neurologic improvement defined as an improvement of ≥8 points on the NIHSS compared with the initial deficit or a score of ≤1 achieved (%)
Time frame: at 24 hours
Major neurologic improvement defined as an improvement of ≥8 points on the NIHSS compared with the initial deficit or a score of ≤1 achieved (%)
Time frame: at 7 days
Symptomatic intracerebral hemorrhage (sICH) (%)
Time frame: within 36 hours
Parenchymal hematoma (PH) (%)
Time frame: within 36 hours
Mortality (%)
Time frame: within 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2025.
- Derived from this study: PubMed 40773205Zhou Y, He Y, Campbell BCV, Liebeskind DS, Yuan C, Chen H, Zhang Y, Yi T, Luo Z, Zhang Z, Meng C, Cheng J, Ouyang H, Hu J, Wang F, Zhang S, Fang Q, Hu H, Zhang X, Chen Y, Zhong W, Lansberg MG, Yan S, Lou M; HOPE investigators. Alteplase for Acute Ischemic Stroke at 4.5 to 24 Hours: The HOPE Randomized Clinical Trial. JAMA. 2025 Sep 2;334(9):788-797. doi: 10.1001/jama.2025.12063.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
26 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 Alteplase in people with Stroke, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 26 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 6 inclusion and 18 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: finished, as of the sponsor's last update on 5 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Excellent recovery assessed by the ratio of modefied Rankin Scale (mRS) score of 0-1 (%) (time frame: at 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04879615, which also lists 1 linked publication.
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 5 Mar 2025.