StrokePhase 4NCT03740958
Argatroban Plus R-tPA for Acute Ischemic Stroke
A Phase 4 study testing rt-PA and Argatroban in people with Stroke, run by General Hospital of Shenyang Military Region at 1 site in China.
Trial summary
Acute ischemic stroke (AIS) is the most common type of stroke, which has high rate of morbidity, mortality and disability. A large number of studies have confirmed that the thrombolytic therapy can effectively open blood vessels and improve the functional prognosis of acute ischemic stroke. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Stroke
- What is being tested?
- rt-PA and Argatroban
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 808 participants
- Where
- 1 siteChina
- Study dates
- 21 Dec 2018to 30 Jan 2022
- Phase
- Phase 4
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-80 years old;
- Time from onset to treatment ≤4.5 hours;
- NIHSS ≥ 6
- Diagnosis of ischemic stroke
- Signed informed consent by patient self or legally authorized representatives.
Who cannot join
- mRS≥2;
- History of stroke within 3 months;
- History of intracranial hemorrhage;
- Suspected subarachnoid hemorrhage;
- Intracranial tumour, vascular malformation or arterial aneurysm;
- Major surgery within 1 month;
Show all 16Show fewer
- Systolic pressure ≥180 mmHg or diastolic pressure ≥110 mmHg;
- Platelet count < 105/mm3;
- Heparin therapy or oral anticoagulation therapy within 48 hours;
- Abnormal APTT;
- Thrombin or Xa factor inhibitor;
- Severe disease with a life expectancy of less than 3 months;
- Blood glucose < 50 mg/dL (2.7mmol/L);
- Patients who have received any other investigational drug or device within 3 months;
- Pregnancy;
- Researchers consider patients inappropriate to participate in the registry.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Argatroban Plus R-tPA for Acute Ischemic Stroke: a Prospective, Random, Open Label, Blinded Assessment of Outcome Multi-center Study
Acute ischemic stroke (AIS) is the most common type of stroke, which has high rate of morbidity, mortality and disability. A large number of studies have confirmed that the thrombolytic therapy can effectively open blood vessels and improve the functional prognosis of acute ischemic stroke. Therefore, all guidelines recommend intravenous thrombolysis as the first treatment of ischemic stroke patients within 4.5 hours of onset. However, about 1/3 patients receiving thrombolysis will have good prognosis, while a large number of patients will still be disabled and even dead. How to improve the neurological prognosis of thrombolytic patients has been a hot topic in the world.
Recent studies have found that the combined application of argatroban and rt-PA in the treatment of AIS might improve the clinical prognosis and not significantly increase bleeding. Some studies have reported that the combined application of argatroban and rt-PA could improve the blood vessel opening rate, and prevent re-occlusion after opening.
Based on the discussion, the present study is designed to explore the efficacy and safety of argatroban plus rt-PA in the treatment of AIS.
- Conditions
- Stroke
- Being tested
- rt-PA, Argatroban
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rt-PADrug
Intravenous throbolysis with 0.9mg/kg rtPA
ArgatrobanDrug
100 ug/kg bolus over 3 to 5 minutes was administered intravenously, followed by a continuous Argatroban infusion of 1.0 ug/kg per minute for 48 hours adjusted to a target activated partial thromboplastin time of 1.75 X baseline (about 10%)
| Study group | Role | What they receive |
|---|---|---|
| Argatroban combined with rt-PA | Experimental | Drug: Argatroban combined with rt-PA Argatroban as a 100 ug/kg bolus over 3 to 5 minutes was administered intravenously within 1 hour of the tPA bolus followed by a continuous Argatroban infusion of 1.0 ug/kg per minute for 48 hours adjusted to a target activated partial thromboplastin time of 1.75 X baseline (about 10%) Receives: Drug: rt-PA; Drug: Argatroban |
| rt-PA | Active comparator | Drug: rt-PA Intravenous throbolysis with 0.9mg/kg rtPA. Receives: Drug: rt-PA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of mRS (0-1）
Measured: 90±7 days
Secondary outcomes (5)
Proportion of mRS (0-2）
Measured: 90±7 days
proportion of more than 2 decrease in NIHSS score
NIHSS, National Institute of Health stroke scale
Measured: 48 hours
proportion of early neurological deterioration
Early neurological deterioration, defined as more than 4 increase in National Institute of Health stroke scale score
Measured: 48 hours
Vascular Events
The occurence of stroke or other vascular events
Measured: 90±7 days
symptomatic intracranial hemorrhage
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2018
- Study start21 Dec 2018
- Primary completion30 Jan 2022
- Study completion30 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 808 participants (actual)
Sponsor and investigators
- Lead sponsor
- General Hospital of Shenyang Military Region
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hui-Sheng Chen, General Hospital of Shenyang Military Region
- Investigators
- Huisheng Chen, Doctor, Study chair, Neurology Department
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03740958
- Sponsor's protocol ID
- k （2018）45
- Status last verified
- Feb 2022
- First submitted
- 12 Nov 2018
- Last updated
- 22 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chen MR, Liu F, Nguyen TN, Chen HS. Circadian Rhythm and Efficacy of Argatroban in Ischemic Stroke with Alteplase: A Post Hoc Analysis of the ARAIS Trial. CNS Drugs. 2026 May;40(5):687-695. doi: 10.1007/s40263-026-01270-3. Epub 2026 Feb 12.
PubMed 41678142Cui Y, Wang EQ, Wang YH, Chen HS. Efficacy of argatroban plus alteplase according to time from onset to thrombolysis in acute ischemic stroke: a prespecified post-hoc analysis of the ARAIS trial. Front Neurol. 2025 Jun 25;16:1582513. doi: 10.3389/fneur.2025.1582513. eCollection 2025.
PubMed 40635702Chen HS, Cui Y, Zhou ZH, Dai YJ, Li GH, Peng ZL, Zhang Y, Liu XD, Yuan ZM, Jiang CH, Yang QC, Duan YJ, Ma GB, Zhao LW, Wang RX, Sun YL, Shen L, Wang EQ, Wang LH, Feng YF, Wang FY, Zou RL, Yang HP, Wang K, Wang DL, Wang YL; ARAIS Investigators. Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial. JAMA. 2023 Feb 28;329(8):640-650. doi: 10.1001/jama.2023.0550.
PubMed 36757755Yang Y, Zhou Z, Pan Y, Chen H, Wang Y; ARAIS Protocol Steering Group. Randomized trial of argatroban plus recombinant tissue-type plasminogen activator for acute ischemic stroke (ARAIS): Rationale and design. Am Heart J. 2020 Jul;225:38-43. doi: 10.1016/j.ahj.2020.04.003. Epub 2020 Apr 8.
PubMed 32485328
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Argatroban Plus R-tPA for Acute Ischemic Stroke: a Prospective, Random, Open Label, Blinded Assessment of Outcome Multi-center Study
- ClinicalTrials.gov ID
- NCT03740958
- Acronym / sponsor ID
- k （2018）45
- Conditions
- Stroke
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 808 participants (actual)
- Lead sponsor
- General Hospital of Shenyang Military RegionUniversity, hospital or other
- Study start
- 21 Dec 2018 (actual)
- Primary completion
- 30 Jan 2022 (actual)
- Study completion
- 30 Jan 2022 (actual)
- First posted
- 14 Nov 2018 (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.
Acute ischemic stroke (AIS) is the most common type of stroke, which has high rate of morbidity, mortality and disability. A large number of studies have confirmed that the thrombolytic therapy can effectively open blood vessels and improve the functional prognosis of acute ischemic stroke. Therefore, all guidelines recommend intravenous thrombolysis as the first treatment of ischemic stroke patients within 4.5 hours of onset. However, about 1/3 patients receiving thrombolysis will have good prognosis, while a large number of patients will still be disabled and even dead. How to improve the neurological prognosis of thrombolytic patients has been a hot topic in the world.
Recent studies have found that the combined application of argatroban and rt-PA in the treatment of AIS might improve the clinical prognosis and not significantly increase bleeding. Some studies have reported that the combined application of argatroban and rt-PA could improve the blood vessel opening rate, and prevent re-occlusion after opening.
Based on the discussion, the present study is designed to explore the efficacy and safety of argatroban plus rt-PA in the treatment of AIS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Argatroban combined with rt-PA | Experimental | Drug: rt-PA, Drug: ArgatrobanDrug: Argatroban combined with rt-PA Argatroban as a 100 ug/kg bolus over 3 to 5 minutes was administered intravenously within 1 hour of the tPA bolus followed by a continuous Argatroban infusion of 1.0 ug/kg per minute for 48 hours adjusted to a target activated partial thromboplastin time of 1.75 X baseline (about 10%) |
| rt-PA | Active comparator | Drug: rt-PADrug: rt-PA Intravenous throbolysis with 0.9mg/kg rtPA. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 18-80 years old;
- Time from onset to treatment ≤4.5 hours;
- NIHSS ≥ 6
- Diagnosis of ischemic stroke
- Signed informed consent by patient self or legally authorized representatives.
Key exclusion criteria (16 listed)
- mRS≥2;
- History of stroke within 3 months;
- History of intracranial hemorrhage;
- Suspected subarachnoid hemorrhage;
- Intracranial tumour, vascular malformation or arterial aneurysm;
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 |
|---|---|---|
| rt-PAIntravenous throbolysis with 0.9mg/kg rtPA | Drug | Argatroban combined with rt-PA, rt-PA |
| Argatroban100 ug/kg bolus over 3 to 5 minutes was administered intravenously, followed by a continuous Argatroban infusion of 1.0 ug/kg per minute for 48 hours adjusted to a target activated partial thromboplastin time of 1.75 X baseline (about 10%) | Drug | Argatroban combined with rt-PA |
Primary outcome
Proportion of mRS (0-1）
Time frame: 90±7 days
5 secondary outcomes
Proportion of mRS (0-2）
Time frame: 90±7 days
proportion of more than 2 decrease in NIHSS score
Time frame: 48 hours
proportion of early neurological deterioration
Time frame: 48 hours
Vascular Events
Time frame: 90±7 days
symptomatic intracranial hemorrhage
Time frame: 48 hours
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 22 Feb 2022.
- Derived from this study: PubMed 41678142Chen MR, Liu F, Nguyen TN, Chen HS. Circadian Rhythm and Efficacy of Argatroban in Ischemic Stroke with Alteplase: A Post Hoc Analysis of the ARAIS Trial. CNS Drugs. 2026 May;40(5):687-695. doi: 10.1007/s40263-026-01270-3. Epub 2026 Feb 12.
- Derived from this study: PubMed 40635702Cui Y, Wang EQ, Wang YH, Chen HS. Efficacy of argatroban plus alteplase according to time from onset to thrombolysis in acute ischemic stroke: a prespecified post-hoc analysis of the ARAIS trial. Front Neurol. 2025 Jun 25;16:1582513. doi: 10.3389/fneur.2025.1582513. eCollection 2025.
- Derived from this study: PubMed 36757755Chen HS, Cui Y, Zhou ZH, Dai YJ, Li GH, Peng ZL, Zhang Y, Liu XD, Yuan ZM, Jiang CH, Yang QC, Duan YJ, Ma GB, Zhao LW, Wang RX, Sun YL, Shen L, Wang EQ, Wang LH, Feng YF, Wang FY, Zou RL, Yang HP, Wang K, Wang DL, Wang YL; ARAIS Investigators. Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial. JAMA. 2023 Feb 28;329(8):640-650. doi: 10.1001/jama.2023.0550.
- Derived from this study: PubMed 32485328Yang Y, Zhou Z, Pan Y, Chen H, Wang Y; ARAIS Protocol Steering Group. Randomized trial of argatroban plus recombinant tissue-type plasminogen activator for acute ischemic stroke (ARAIS): Rationale and design. Am Heart J. 2020 Jul;225:38-43. doi: 10.1016/j.ahj.2020.04.003. Epub 2020 Apr 8.
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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.
Huisheng Chen, Doctor study chair
Neurology Department
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing rt-PA and Argatroban in people with Stroke, run by General Hospital of Shenyang Military Region at 1 site 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 5 inclusion and 16 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 22 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Proportion of mRS (0-1） (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?
On the ClinicalTrials.gov record for NCT03740958, which also lists 4 linked publications.
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 22 Feb 2022.