China Antihypertensive Trial in Acute Ischemic Stroke II

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

Interventions

OTHER

Early antihypertensive treatment

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.

OTHER

Delayed antihypertensive treatment

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.

Sponsors & Collaborators

• Beijing Tiantan Hospital

  collaborator OTHER

• Soochow University

  collaborator OTHER

• Tulane University

  lead OTHER

Principal Investigators

• Jiang He, MD, PhD · Tulane University

• Yilong Wang, MD, PhD · Beijing Tiantan Hospital

• Liping Liu, MD, PhD · Beijing Tiantan Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

40 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-06-13

Primary Completion

2022-10-15

Completion

2023-01-15

Countries

• China

Study Locations