Acute Ischemic StrokePhase 3CATIS-2NCT03479554
China Antihypertensive Trial in Acute Ischemic Stroke II
A Phase 3 study testing Early antihypertensive treatment and Delayed antihypertensive treatment in people with Acute Ischemic Stroke, run by Tulane University at 1 site in China.
Trial summary
The investigators propose to conduct a multicenter randomized trial to test the primary hypothesis of whether early antihypertensive treatment starting between the first 24-48 hours after the onset of an acute ischemic stroke will reduce the risk of composite case-fatality and major disability (modified Rankin Scale… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Acute Ischemic Stroke
- What is being tested?
- Early antihypertensive treatment and Delayed antihypertensive treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4,810 participants
- Where
- 1 siteChina
- Study dates
- 13 Jun 2018to 15 Jan 2023
- 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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged ≥40 years
- Acute ischemic stroke confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) of the head
- Stroke onset within 24-48 hours*
- Systolic blood pressure between 140-200 mmHg and diastolic blood pressure between 80-120 mmHg
Who cannot join
- Hemorrhagic stroke confirmed by CT or MRI of the head
- CT or MRI-diagnosed vascular malformation, tumor, abscess, or other major non-ischemic brain disease (e.g., multiple sclerosis)
- Extracranial or intracranial artery stenosis (≥70%) in both sides or the affected side based on imagine study
- Stroke caused by arteritis, migraine, vasospasm, or substance abuse
- Severe stroke (NIHSS score of ≥21)
- Coma (Glasgow Coma Scale [GCS] score <8)
Show all 22Show fewer
- Preceding moderate or severe dependency (modified Rankin scale [mRS] score 3-5)
- Planned or probable revascularization (any angioplasty or vascular surgery) within 3 months after screening
- Intravenous thrombolytic therapy (such as intravenous rtPA) or mechanical thrombectomy
- Severe heart failure (NY Heart Association class III and IV) or left ventricular ejection fraction <35%
- Myocardial infarction or unstable angina within past 3 months
- History of atrial fibrillation.
- History of aortic dissection
- History of all-cause dementia
- Difficult-to-control hypertension (systolic blood pressure ≥170 mmHg despite use of ≥4 antihypertensive medications for ≥6 months)
- Acute renal failure or dialysis or estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m2
- Any clinical conditions judged by the clinic team to likely limit the adherence to study procedures
- Inability to understand and/or follow research procedures due to mental, cognitive, or emotional disorders
- Unable to participate in the follow-up examination (e.g., cannot travel to the participating hospital)
- Participation in another clinical trial within 30 days
- Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control
- Failure to obtain informed consent from a participant
Trial locations and contacts
1 site in 1 country.
About this study
The investigators propose to conduct a multicenter randomized trial to test the primary hypothesis of whether early antihypertensive treatment starting between the first 24-48 hours after the onset of an acute ischemic stroke will reduce the risk of composite case-fatality and major disability (modified Rankin Scale score ≥3) at three months compared to delayed antihypertensive treatment (starting on day 8 after stroke onset). In the proposed China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2), the investigators will recruit 4,776 patients from 100 hospitals within the China-US Collaborative Stroke Clinical Trial Network. Eligibility criteria for the trial participants include age ≥40 years, acute ischemic stroke confirmed by CT/MRI, symptom onset between 24-48 hours, and average systolic blood pressure (BP) between 140-200 mmHg at randomization. Patients with extracranial or intracranial artery stenosis (≥70%) in both sides or the affected side, NIH Stroke Scale score of ≥21, Glasgow Coma Scale score <8, preceding moderate or severe dependency (modified Rankin scale score 3-5), revascularization, intravenous thrombolytic therapy or mechanical thrombectomy will be excluded. All eligible patients will discontinue their home antihypertensive medications. Patients admitted within 24 hours of symptom onset will require a reevaluation prior to randomization at 24 hours after stroke onset. After randomization, patients in the early treatment group will immediately receive antihypertensive treatment aimed at lowering average systolic BP by 10-20% within the first 24 hours and achieving an average BP <140/90 mmHg within seven days. Patients in the delayed treatment group will discontinue antihypertensive medications for the first seven days. After seven days, both groups will receive antihypertensive treatment with a BP goal of <140/90 mmHg. The primary study endpoint is a composite outcome of death and major disability at three months. The major secondary endpoint will be the first recurrent stroke (hemorrhagic or ischemic) over three-month follow-up after randomization. Other secondary endpoints include ordered 7-level categorical score of the modified Rankin Scale, all-cause mortality, and major vascular events at three months. The proposed study provides 85% statistical power to detect a 15% reduction in the composite outcome of death and major disability over three months at a significance level of 0.05 for a two-sided test. Based on experience from our previous trials, we assumed a 25% event rate of the primary study endpoint and potential loss to follow-up of 5% over three months. The CATIS-2 trial will provide important information for the development of clinical guidelines in the early management of BP among patients with acute ischemic stroke for reducing mortality and major disability.
Read the detailed description
Stroke is the leading cause of death in China and the second leading cause of death in the world. In addition, stroke is the leading cause of long-term disability worldwide and a major financial burden to society. It is estimated that there are probably more than 3 million new strokes every year in China. In 2013, more than 1.9 million Chinese adults died from stroke, which represented an increase of 47.7% from 1.3 million in 1990.
Elevated blood pressure (BP) is common in the acute phase of ischemic stroke, occurring in ≥75% of all patients. The early BP increase following ischemic stroke often reflects uncontrolled chronic hypertension. In addition, the potential causes of this transient rise include disturbed cerebral autoregulation, damage or compression of brain regions that regulate BP, neuroendocrine disturbance, and non-specific mechanisms such as headache, urine retention, and psychological stress. Several clinical trials have tested the effects of immediate BP lowering on adverse clinical outcomes in patients with acute ischemic stroke and showed a neutral effect on death or dependency. The China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) suggested a beneficial effect of BP lowering on death or major disability (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.55-0.96, p=0.03) and recurrent stroke (OR 0.25, 95% CI 0.08-0.74, p=0.01) among patients with acute ischemic stroke who received antihypertensive treatment between 24-48 hours in a subgroup analysis. There are important knowledge gaps in BP management in acute ischemic stroke, such as when is the optimal time for initiation of antihypertensive treatment.
The investigators propose to conduct a multicenter randomized controlled trial to test the primary hypothesis of whether early antihypertensive treatment starting between the first 24-48 hours after the onset of an acute ischemic stroke will reduce the risk of composite case-fatality and major disability (modified Rankin scale score ≥3) at three months compared to delayed antihypertensive treatment (starting on day 8 after stroke onset). Patients with acute ischemic stroke will be randomly assigned within the first 24-48 hours after stroke onset to the early and delayed treatment groups. Patients in the early treatment group will immediately receive antihypertensive treatment aimed at lowering average systolic BP by 10-20% (with a mean reduction of 15%) within the first 24 hours, achieving an average systolic/diastolic BP <140/90 mmHg within seven days, and maintaining this level afterward. Patients in the delayed treatment group will discontinue antihypertensive medications for the first seven days. After then, both groups will receive antihypertensive treatment with an average systolic/diastolic BP goal of <140/90 mmHg. The primary study endpoint will be a composite outcome of death and major disability (modified Rankin Scale score ≥3) at three months after randomization. The major secondary endpoint will be the first recurrent stroke (hemorrhagic or ischemic) within three months. Other secondary endpoints include ordered 7-level categorical score of the modified Rankin Scale, all-cause mortality, and major vascular events at three months.
In the proposed China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2), the investigators will recruit 4,776 patients (2,388 for each group) from 100 hospitals within the China Stroke Clinical Research Network. Eligibility criteria for the trial participants include age ≥40 years, acute ischemic stroke confirmed by computed tomography (CT) or magnetic resonance imaging (MRI), symptom onset between 24-48 hours, and an average systolic BP between 140-200 mmHg. The proposed study provides 85% statistical power to detect a 15% reduction in the primary study endpoint at three months at a significance level of 0.05 for a two-sided test. Based on experience from our previous CATIS trial, we assumed an event rate of 25% for the primary study outcome and potential loss to follow-up of 5% over three months. To achieve the CATIS-2 study objectives, we plan to:
- Recruit and randomize 4,776 eligible patients (2,388 for each group) to the early antihypertensive treatment group or the delayed antihypertensive treatment group according to the study eligibility criteria;
- Achieve and maintain target treatment goals for BP in the randomization groups;
- Follow a study-wide strategy to encourage a standard of care based on clinical guidelines for the treatment of acute ischemic stroke other than BP for all participants;
- Obtain follow-up data on clinical endpoints, neurological and functional status for each participant according to the study protocol; and
- Estimate the effect of early antihypertensive treatment vs. delayed treatment on the primary and secondary endpoints according to intention-to-treat analysis and conduct predefined subgroup analyses.
The CATIS-2 study will provide important information for the development of clinical guidelines in the early management of BP among patients with acute ischemic stroke for reducing mortality and major disability.
- Conditions
- Acute Ischemic Stroke
- Being tested
- Early antihypertensive treatment, Delayed antihypertensive treatment
- Keywords
- antihypertensive treatment
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early antihypertensive treatmentOther
The CATIS 2 trial is designed to test BP reduction strategies-early antihypertensive treatment vs. delayed antihypertensive treatment-rather than test the efficacy of individual antihypertensive drugs. Several antihypertensive agents, including angiotensin-converting enzyme inhibitors, calcium channel blockers, and diuretics will be used in the trial.
BP-lowering treatment will start immediately after randomization in the early antihypertensive treatment group. The target treatment goals are:
- Step 1 (within 24 hours after randomization): To lower systolic BP by 10-20% with an average of 15% (but systolic BP not lower than 130 mmHg and diastolic BP not lower than 80 mmHg) within the first 24 hours after randomization based on the participant's admission BP levels.
- Step 2 (within 7 days after randomization): To achieve systolic BP below 140 mmHg (but not lower than 120 mmHg) and diastolic BP below 90 mmHg (but not lower than 70 mmHg) and maintain this BP level afterward.
Delayed antihypertensive treatmentOther
All home antihypertensive medications will be discontinued in the first seven days after randomization. Study participants will receive antihypertensive treatment on day eight after randomization and will target systolic BP <140 mmHg (but not lower than 120 mmHg) and diastolic BP <90 mmHg (but not lower than 70 mmHg) in two weeks. A BP check-up visit will be conducted in two weeks. If BP treatment goal is not achieved, antihypertensive medication will be titrated or a new medication will be added.
| Study group | Role | What they receive |
|---|---|---|
| Early antihypertensive treatment group | Experimental | BP-lowering treatment will start immediately after randomization in the early antihypertensive treatment group. Receives: Other: Early antihypertensive treatment |
| Delayed antihypertensive treatment group | Active comparator | All home antihypertensive medications will be discontinued in the first seven days after randomization. Study participants will receive antihypertensive treatment on day eight after randomization. Receives: Other: Delayed antihypertensive treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite outcome of death and major disability
The primary endpoint for the CATIS-2 trial is a composite outcome of death and major disability (modified Rankin score ≥3) at 3 months.
Measured: At 3 months
Secondary outcomes (4)
Recurrent stroke
The first recurrent stroke event (hemorrhagic or ischemic) over three months of follow-up.
Measured: At 3 months
Modified Rankin Scale
Ordered 7-level categorical score of the modified Rankin Scale
Measured: At 3 months
All-cause mortality
Total mortality from all causes
Measured: At 3 months
Major vascular disease events
Vascular deaths, non-fatal stroke, non-fatal myocardial infarction, coronary revascularization, hospitalized or treated angina, and hospitalized or treated congestive heart failure
Measured: At 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2018
- Study start13 Jun 2018
- Primary completion15 Oct 2022
- Study completion15 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- 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
- Model description
- Randomization will be conducted centrally at the SDCC. The randomization will be stratified by participating hospitals and use of antihypertensive medication. In each stratum, patients will be randomly assigned to the early antihypertensive treatment group or the delayed antihypertensive treatment group within each block. The block size will be random among 4, 6, and 8. The early BP lowering group will receive antihypertensive treatment immediately according to the study protocol, and the delayed BP lowering group will discontinue antihypertensive treatment for the first seven days after randomization. The randomization schedules will be generated using SAS PROC PLAN in SAS and will be concealed at the SDCC. When an eligible participant is ready for randomization, the site investigator/study coordinator will log-in to a password-protected website to obtain the randomization assignment.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 4,810 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tulane University
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing Tiantan Hospital, Soochow University
- Responsible party
- Principal investigator, Jiang He, MD, PhD, Tulane University
- Investigators
- Jiang He, MD, PhD, Principal investigator, Tulane UniversityYilong Wang, MD, PhD, Principal investigator, Beijing Tiantan HospitalLiping Liu, MD, PhD, Principal investigator, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03479554
- Sponsor's protocol ID
- 1109725
- Acronym
- CATIS-2
- Status last verified
- Jul 2023
- First submitted
- 9 Mar 2018
- Last updated
- 1 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is not a plan to make IPD available. Sharing IPD will require IRB approval from Tiantan Hospital and other participating institutes in China.
Publications
Wang M, Wei Y, Zhao Z, Liu X, Nie X, Duan W, Zhang Z, Zheng L, Law ZK, Pan Y, Liu L. Cognitive reserve and risk of poststroke cognitive impairment in acute ischaemic stroke: post hoc analysis of CATIS-2. Stroke Vasc Neurol. 2026 Oct 6:svn-2026-005809. doi: 10.1136/svn-2026-005809. Online ahead of print.
PubMed 42838606Liu D, Wei Y, Xie X, Wang M, Pan Y, Wang A, Liu J, Nie X, Duan W, Liu X, Zhang Z, Zhao Z, Zhong C, Xu T, Jiang Y, Jing J, Meng X, Wang Y, Zhang Y, Wang Y, Zhan S, Liu L. Renal function and effect of early antihypertensive therapy in acute ischaemic stroke: a subgroup analysis of the CATIS-2 trial. Stroke Vasc Neurol. 2026 May 27:svn-2025-005065. doi: 10.1136/svn-2025-005065. Online ahead of print.
PubMed 42203475Zhao W, Wei Y, Pan Y, Wang M, Xie X, Wang A, Zhao Z, Liu D, Nie X, Liu X, Zheng L, Zhong C, Zhang Y, Liu L. Initial systolic blood pressure, antihypertensive treatment timing and outcomes in acute ischemic stroke: a subgroup analysis of CATIS-2 trial. J Hypertens. 2026 Jul 1;44(7):1129-1136. doi: 10.1097/HJH.0000000000004303. Epub 2026 Mar 18.
PubMed 41860186Zhong C, Wang M, Liu D, Wei Y, Wang M, Peng Y, Chen J, Pan Y, Xu T, Wang Y, He J, Wang Y, Zhang Y, Liu L, Xie X. Antihypertensive Treatments After Acute Ischemic Stroke: to Continue or Not? Hypertension. 2026 Feb;83(2):e25575. doi: 10.1161/HYPERTENSIONAHA.125.25575. Epub 2025 Dec 5.
PubMed 41347304Xie X, Zhong C, Liu X, Pan Y, Wang A, Wei Y, Liu D, Xu T, Jiang Y, Wang M, Jing J, Meng X, Obst K, Chen CS, Wang D, Wang Y, Zhang Y, He J, Wang Y, Liu L. Early Versus Delayed Antihypertensive Treatment After Acute Ischemic Stroke by Hypertension History. Stroke. 2025 Mar;56(3):631-639. doi: 10.1161/STROKEAHA.124.049242. Epub 2025 Jan 14.
PubMed 39807580Wei Y, Xie X, Pan Y, Wang M, Wang A, Liu D, Zhao Z, Nie X, Duan W, Liu X, Zhang Z, Liu J, Zheng L, Shen S, Zhong C, Xu T, Jiang Y, Jing J, Meng X, Obst K, Chen CS, Li H, Leng X, Wang D, Wang Y, Zhang Y, He J, Wang Y, Liu L. Early vs Delayed Antihypertensive Treatment in Acute Single Subcortical Infarction: A Secondary Analysis of the CATIS-2 Randomized Clinical Trial. JAMA Netw Open. 2024 Aug 1;7(8):e2430820. doi: 10.1001/jamanetworkopen.2024.30820.
PubMed 39212990Liu L, Xie X, Pan Y, Wang A, Wei Y, Liu J, Nie X, Liu D, Zhao Z, Wang P, Shen S, Zhong C, Xu T, Wang D, Wang GC, Song D, Ma Y, Zhao J, Jiang Y, Jing J, Meng X, Obst K, Chen CS, Wang D, Wang Y, Zhang Y, Wang Y, He J; CATIS-2 Investigators. Early versus delayed antihypertensive treatment in patients with acute ischaemic stroke: multicentre, open label, randomised, controlled trial. BMJ. 2023 Oct 9;383:e076448. doi: 10.1136/bmj-2023-076448.
PubMed 37813418Liu L, Wang Y, Xie X, Liu D, Wang A, Wang P, Shen S, Zhong C, Wei Y, Xu T, Pan Y, Jiang Y, Meng X, Wang D, Zhang Y, He J, Wang Y. China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2): rationale and design. Stroke Vasc Neurol. 2021 Jun;6(2):286-290. doi: 10.1136/svn-2020-000828. Epub 2021 Mar 16.
PubMed 33727409
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- China Antihypertensive Trial in Acute Ischemic Stroke II
- ClinicalTrials.gov ID
- NCT03479554
- Acronym / sponsor ID
- CATIS-2 / 1109725
- Conditions
- Acute Ischemic Stroke
- Keywords
- antihypertensive treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4,810 participants (actual)
- Lead sponsor
- Tulane UniversityUniversity, hospital or other
- Collaborators
- Beijing Tiantan Hospital, Soochow University
- Study start
- 13 Jun 2018 (actual)
- Primary completion
- 15 Oct 2022 (actual)
- Study completion
- 15 Jan 2023 (actual)
- First posted
- 27 Mar 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.
The investigators propose to conduct a multicenter randomized trial to test the primary hypothesis of whether early antihypertensive treatment starting between the first 24-48 hours after the onset of an acute ischemic stroke will reduce the risk of composite case-fatality and major disability (modified Rankin Scale score ≥3) at three months compared to delayed antihypertensive treatment (starting on day 8 after stroke onset). In the proposed China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2), the investigators will recruit 4,776 patients from 100 hospitals within the China-US Collaborative Stroke Clinical Trial Network. Eligibility criteria for the trial participants include age ≥40 years, acute ischemic stroke confirmed by CT/MRI, symptom onset between 24-48 hours, and average systolic blood pressure (BP) between 140-200 mmHg at randomization. Patients with extracranial or intracranial artery stenosis (≥70%) in both sides or the affected side, NIH Stroke Scale score of ≥21, Glasgow Coma Scale score <8, preceding moderate or severe dependency (modified Rankin scale score 3-5), revascularization, intravenous thrombolytic therapy or mechanical thrombectomy will be excluded. All eligible patients will discontinue their home antihypertensive medications. Patients admitted within 24 hours of symptom onset will require a reevaluation prior to randomization at 24 hours after stroke onset. After randomization, patients in the early treatment group will immediately receive antihypertensive treatment aimed at lowering average systolic BP by 10-20% within the first 24 hours and achieving an average BP <140/90 mmHg within seven days. Patients in the delayed treatment group will discontinue antihypertensive medications for the first seven days. After seven days, both groups will receive antihypertensive treatment with a BP goal of <140/90 mmHg. The primary study endpoint is a composite outcome of death and major disability at three months. The major secondary endpoint will be the first recurrent stroke (hemorrhagic or ischemic) over three-month follow-up after randomization. Other secondary endpoints include ordered 7-level categorical score of the modified Rankin Scale, all-cause mortality, and major vascular events at three months. The proposed study provides 85% statistical power to detect a 15% reduction in the composite outcome of death and major disability over three months at a significance level of 0.05 for a two-sided test. Based on experience from our previous trials, we assumed a 25% event rate of the primary study endpoint and potential loss to follow-up of 5% over three months. The CATIS-2 trial will provide important information for the development of clinical guidelines in the early management of BP among patients with acute ischemic stroke for reducing mortality and major disability.
Detailed description
Stroke is the leading cause of death in China and the second leading cause of death in the world. In addition, stroke is the leading cause of long-term disability worldwide and a major financial burden to society. It is estimated that there are probably more than 3 million new strokes every year in China. In 2013, more than 1.9 million Chinese adults died from stroke, which represented an increase of 47.7% from 1.3 million in 1990.
Elevated blood pressure (BP) is common in the acute phase of ischemic stroke, occurring in ≥75% of all patients. The early BP increase following ischemic stroke often reflects uncontrolled chronic hypertension. In addition, the potential causes of this transient rise include disturbed cerebral autoregulation, damage or compression of brain regions that regulate BP, neuroendocrine disturbance, and non-specific mechanisms such as headache, urine retention, and psychological stress. Several clinical trials have tested the effects of immediate BP lowering on adverse clinical outcomes in patients with acute ischemic stroke and showed a neutral effect on death or dependency. The China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) suggested a beneficial effect of BP lowering on death or major disability (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.55-0.96, p=0.03) and recurrent stroke (OR 0.25, 95% CI 0.08-0.74, p=0.01) among patients with acute ischemic stroke who received antihypertensive treatment between 24-48 hours in a subgroup analysis. There are important knowledge gaps in BP management in acute ischemic stroke, such as when is the optimal time for initiation of antihypertensive treatment.
The investigators propose to conduct a multicenter randomized controlled trial to test the primary hypothesis of whether early antihypertensive treatment starting between the first 24-48 hours after the onset of an acute ischemic stroke will reduce the risk of composite case-fatality and major disability (modified Rankin scale score ≥3) at three months compared to delayed antihypertensive treatment (starting on day 8 after stroke onset). Patients with acute ischemic stroke will be randomly assigned within the first 24-48 hours after stroke onset to the early and delayed treatment groups. Patients in the early treatment group will immediately receive antihypertensive treatment aimed at lowering average systolic BP by 10-20% (with a mean reduction of 15%) within the first 24 hours, achieving an average systolic/diastolic BP <140/90 mmHg within seven days, and maintaining this level afterward. Patients in the delayed treatment group will discontinue antihypertensive medications for the first seven days. After then, both groups will receive antihypertensive treatment with an average systolic/diastolic BP goal of <140/90 mmHg. The primary study endpoint will be a composite outcome of death and major disability (modified Rankin Scale score ≥3) at three months after randomization. The major secondary endpoint will be the first recurrent stroke (hemorrhagic or ischemic) within three months. Other secondary endpoints include ordered 7-level categorical score of the modified Rankin Scale, all-cause mortality, and major vascular events at three months.
In the proposed China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2), the investigators will recruit 4,776 patients (2,388 for each group) from 100 hospitals within the China Stroke Clinical Research Network. Eligibility criteria for the trial participants include age ≥40 years, acute ischemic stroke confirmed by computed tomography (CT) or magnetic resonance imaging (MRI), symptom onset between 24-48 hours, and an average systolic BP between 140-200 mmHg. The proposed study provides 85% statistical power to detect a 15% reduction in the primary study endpoint at three months at a significance level of 0.05 for a two-sided test. Based on experience from our previous CATIS trial, we assumed an event rate of 25% for the primary study outcome and potential loss to follow-up of 5% over three months. To achieve the CATIS-2 study objectives, we plan to:
- Recruit and randomize 4,776 eligible patients (2,388 for each group) to the early antihypertensive treatment group or the delayed antihypertensive treatment group according to the study eligibility criteria;
- Achieve and maintain target treatment goals for BP in the randomization groups;
- Follow a study-wide strategy to encourage a standard of care based on clinical guidelines for the treatment of acute ischemic stroke other than BP for all participants;
- Obtain follow-up data on clinical endpoints, neurological and functional status for each participant according to the study protocol; and
- Estimate the effect of early antihypertensive treatment vs. delayed treatment on the primary and secondary endpoints according to intention-to-treat analysis and conduct predefined subgroup analyses.
The CATIS-2 study will provide important information for the development of clinical guidelines in the early management of BP among patients with acute ischemic stroke for reducing mortality and major disability.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomization will be conducted centrally at the SDCC. The randomization will be stratified by participating hospitals and use of antihypertensive medication. In each stratum, patients will be randomly assigned to the early antihypertensive treatment group or the delayed antihypertensive treatment group within each block. The block size will be random among 4, 6, and 8. The early BP lowering group will receive antihypertensive treatment immediately according to the study protocol, and the delayed BP lowering group will discontinue antihypertensive treatment for the first seven days after randomization. The randomization schedules will be generated using SAS PROC PLAN in SAS and will be concealed at the SDCC. When an eligible participant is ready for randomization, the site investigator/study coordinator will log-in to a password-protected website to obtain the randomization assignment.
| Arm | Type | Receives |
|---|---|---|
| Early antihypertensive treatment group | Experimental | Other: Early antihypertensive treatmentBP-lowering treatment will start immediately after randomization in the early antihypertensive treatment group. |
| Delayed antihypertensive treatment group | Active comparator | Other: Delayed antihypertensive treatmentAll home antihypertensive medications will be discontinued in the first seven days after randomization. Study participants will receive antihypertensive treatment on day eight after randomization. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men and women aged ≥40 years
- Acute ischemic stroke confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) of the head
- Stroke onset within 24-48 hours*
- Systolic blood pressure between 140-200 mmHg and diastolic blood pressure between 80-120 mmHg
Key exclusion criteria (22 listed)
- Hemorrhagic stroke confirmed by CT or MRI of the head
- CT or MRI-diagnosed vascular malformation, tumor, abscess, or other major non-ischemic brain disease (e.g., multiple sclerosis)
- Extracranial or intracranial artery stenosis (≥70%) in both sides or the affected side based on imagine study
- Stroke caused by arteritis, migraine, vasospasm, or substance abuse
- Severe stroke (NIHSS score of ≥21)
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 |
|---|---|---|
| Early antihypertensive treatmentThe CATIS 2 trial is designed to test BP reduction strategies-early antihypertensive treatment vs. delayed antihypertensive treatment-rather than test the efficacy of individual antihypertensive drugs. Several antihypertensive agents, including angiotensin-converting enzyme inhibitors, calcium channel blockers, and diuretics will be used in the trial. BP-lowering treatment will start immediately after randomization in the early antihypertensive treatment group. The target treatment goals are: * Step 1 (within 24 hours after randomization): To lower systolic BP by 10-20% with an average of 15% (but systolic BP not lower than 130 mmHg and diastolic BP not lower than 80 mmHg) within the first 24 hours after randomization based on the participant's admission BP levels. * Step 2 (within 7 days after randomization): To achieve systolic BP below 140 mmHg (but not lower than 120 mmHg) and diastolic BP below 90 mmHg (but not lower than 70 mmHg) and maintain this BP level afterward. | Other | Early antihypertensive treatment group |
| Delayed antihypertensive treatmentAll home antihypertensive medications will be discontinued in the first seven days after randomization. Study participants will receive antihypertensive treatment on day eight after randomization and will target systolic BP <140 mmHg (but not lower than 120 mmHg) and diastolic BP <90 mmHg (but not lower than 70 mmHg) in two weeks. A BP check-up visit will be conducted in two weeks. If BP treatment goal is not achieved, antihypertensive medication will be titrated or a new medication will be added. | Other | Delayed antihypertensive treatment group |
Primary outcome
Composite outcome of death and major disability
Time frame: At 3 months
The primary endpoint for the CATIS-2 trial is a composite outcome of death and major disability (modified Rankin score ≥3) at 3 months.
4 secondary outcomes
Recurrent stroke
Time frame: At 3 months
Modified Rankin Scale
Time frame: At 3 months
All-cause mortality
Time frame: At 3 months
Major vascular disease events
Time frame: At 3 months
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 1 Aug 2023.
- Derived from this study: PubMed 42838606Wang M, Wei Y, Zhao Z, Liu X, Nie X, Duan W, Zhang Z, Zheng L, Law ZK, Pan Y, Liu L. Cognitive reserve and risk of poststroke cognitive impairment in acute ischaemic stroke: post hoc analysis of CATIS-2. Stroke Vasc Neurol. 2026 Oct 6:svn-2026-005809. doi: 10.1136/svn-2026-005809. Online ahead of print.
- Derived from this study: PubMed 42203475Liu D, Wei Y, Xie X, Wang M, Pan Y, Wang A, Liu J, Nie X, Duan W, Liu X, Zhang Z, Zhao Z, Zhong C, Xu T, Jiang Y, Jing J, Meng X, Wang Y, Zhang Y, Wang Y, Zhan S, Liu L. Renal function and effect of early antihypertensive therapy in acute ischaemic stroke: a subgroup analysis of the CATIS-2 trial. Stroke Vasc Neurol. 2026 May 27:svn-2025-005065. doi: 10.1136/svn-2025-005065. Online ahead of print.
- Derived from this study: PubMed 41860186Zhao W, Wei Y, Pan Y, Wang M, Xie X, Wang A, Zhao Z, Liu D, Nie X, Liu X, Zheng L, Zhong C, Zhang Y, Liu L. Initial systolic blood pressure, antihypertensive treatment timing and outcomes in acute ischemic stroke: a subgroup analysis of CATIS-2 trial. J Hypertens. 2026 Jul 1;44(7):1129-1136. doi: 10.1097/HJH.0000000000004303. Epub 2026 Mar 18.
- Derived from this study: PubMed 41347304Zhong C, Wang M, Liu D, Wei Y, Wang M, Peng Y, Chen J, Pan Y, Xu T, Wang Y, He J, Wang Y, Zhang Y, Liu L, Xie X. Antihypertensive Treatments After Acute Ischemic Stroke: to Continue or Not? Hypertension. 2026 Feb;83(2):e25575. doi: 10.1161/HYPERTENSIONAHA.125.25575. Epub 2025 Dec 5.
- Derived from this study: PubMed 39807580Xie X, Zhong C, Liu X, Pan Y, Wang A, Wei Y, Liu D, Xu T, Jiang Y, Wang M, Jing J, Meng X, Obst K, Chen CS, Wang D, Wang Y, Zhang Y, He J, Wang Y, Liu L. Early Versus Delayed Antihypertensive Treatment After Acute Ischemic Stroke by Hypertension History. Stroke. 2025 Mar;56(3):631-639. doi: 10.1161/STROKEAHA.124.049242. Epub 2025 Jan 14.
- Derived from this study: PubMed 39212990Wei Y, Xie X, Pan Y, Wang M, Wang A, Liu D, Zhao Z, Nie X, Duan W, Liu X, Zhang Z, Liu J, Zheng L, Shen S, Zhong C, Xu T, Jiang Y, Jing J, Meng X, Obst K, Chen CS, Li H, Leng X, Wang D, Wang Y, Zhang Y, He J, Wang Y, Liu L. Early vs Delayed Antihypertensive Treatment in Acute Single Subcortical Infarction: A Secondary Analysis of the CATIS-2 Randomized Clinical Trial. JAMA Netw Open. 2024 Aug 1;7(8):e2430820. doi: 10.1001/jamanetworkopen.2024.30820.
- Derived from this study: PubMed 37813418Liu L, Xie X, Pan Y, Wang A, Wei Y, Liu J, Nie X, Liu D, Zhao Z, Wang P, Shen S, Zhong C, Xu T, Wang D, Wang GC, Song D, Ma Y, Zhao J, Jiang Y, Jing J, Meng X, Obst K, Chen CS, Wang D, Wang Y, Zhang Y, Wang Y, He J; CATIS-2 Investigators. Early versus delayed antihypertensive treatment in patients with acute ischaemic stroke: multicentre, open label, randomised, controlled trial. BMJ. 2023 Oct 9;383:e076448. doi: 10.1136/bmj-2023-076448.
- Derived from this study: PubMed 33727409Liu L, Wang Y, Xie X, Liu D, Wang A, Wang P, Shen S, Zhong C, Wei Y, Xu T, Pan Y, Jiang Y, Meng X, Wang D, Zhang Y, He J, Wang Y. China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2): rationale and design. Stroke Vasc Neurol. 2021 Jun;6(2):286-290. doi: 10.1136/svn-2020-000828. Epub 2021 Mar 16.
- Individual participant dataSharing planned: No. There is not a plan to make IPD available. Sharing IPD will require IRB approval from Tiantan Hospital and other participating institutes in China.
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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.
Jiang He, MD, PhD principal investigator
Tulane University
Yilong Wang, MD, PhD principal investigator
Beijing Tiantan Hospital
Liping Liu, MD, PhD principal investigator
Beijing Tiantan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Early antihypertensive treatment and Delayed antihypertensive treatment in people with Acute Ischemic Stroke, run by Tulane University 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 4 inclusion and 22 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 1 Aug 2023. 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 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?
Composite outcome of death and major disability (time frame: At 3 months). 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 NCT03479554, which also lists 8 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 1 Aug 2023.