China Antihypertensive Trial in Acute Ischemic Stroke II

NCT03479554 | Completed Phase 3 DMC

• 1 other identifier: 1109725
• Study Type: interventional
• Target: 4,810
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Acute Ischemic Stroke

Keywords

antihypertensive treatment

Outcome Measures

Primary Outcomes (1)

• 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.

  At 3 months

Secondary Outcomes (4)

• Recurrent stroke

  At 3 months

• Modified Rankin Scale

  At 3 months

• All-cause mortality

  At 3 months

• Major vascular disease events

  At 3 months

Study Arms (2)

Early antihypertensive treatment group

EXPERIMENTAL

BP-lowering treatment will start immediately after randomization in the early antihypertensive treatment group.

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.

Other: Delayed antihypertensive treatment

Interventions

Early antihypertensive treatment OTHER

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.

Early antihypertensive treatment group

Delayed antihypertensive treatment OTHER

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.

Delayed antihypertensive treatment group

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• Tulane University: lead
• Beijing Tiantan Hospital: collaborator
• Soochow University: collaborator

Study Sites (1)

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100050, China

Location

Related Publications (5)

• Zhong 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.

  PMID: 41347304 DERIVED

• Xie 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.

  PMID: 39807580 DERIVED

• Wei 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.

  PMID: 39212990 DERIVED

• Liu 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.

  PMID: 37813418 DERIVED

• Liu 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.

  PMID: 33727409 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Jiang He, MD, PhD

  Tulane University

  PRINCIPAL INVESTIGATOR

• Yilong Wang, MD, PhD

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

• Liping Liu, MD, PhD

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: The study physicians and nurses will not be masked to patients' randomization assignments because of the different time points for initiating BP treatment between the two randomization groups. The data on BP will also be unmasked because they are management tools for attaining the specific treatment targets. However, the study neurologists and nurses who conduct the neurological and functional assessments and collect clinical outcome data at the baseline and follow-up examinations will be masked to patients' assignments. The members of the Outcome Adjudication Committee will also be masked to patients' randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chair of Epidemiology

Model Details: 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.

Study Record Dates

• First Submitted: March 9, 2018
• First Posted: March 27, 2018
• Study Start: June 13, 2018
• Primary Completion: October 15, 2022
• Study Completion: January 15, 2023
• Last Updated: August 1, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)