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China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2)

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ClinicalTrials.gov Identifier: NCT03479554
Recruitment Status : Recruiting
First Posted : March 27, 2018
Last Update Posted : September 11, 2019
Sponsor:
Collaborators:
Beijing Tiantan Hospital
Soochow University
Information provided by (Responsible Party):
Jiang He, MD, PhD, Tulane University

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 five 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, major vascular events, cognitive impairment, and health-related quality of life 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.

Condition or disease Intervention/treatment Phase
Acute Ischemic Stroke Other: Early antihypertensive treatment Other: Delayed antihypertensive treatment Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4776 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: China Antihypertensive Trial in Acute Ischemic Stroke II
Actual Study Start Date : January 1, 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Early antihypertensive treatment group
BP-lowering treatment will start immediately after randomization in the early antihypertensive treatment group.
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 5 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.

Active Comparator: Delayed antihypertensive treatment group
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
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Recurrent stroke [ Time Frame: At 3 months ]
    The first recurrent stroke event (hemorrhagic or ischemic) over three months of follow-up.

  2. Modified Rankin Scale [ Time Frame: At 3 months ]
    Ordered 7-level categorical score of the modified Rankin Scale

  3. All-cause mortality [ Time Frame: At 3 months ]
    Total mortality from all causes

  4. Major vascular disease events [ Time Frame: At 3 months ]
    Vascular deaths, non-fatal stroke, non-fatal myocardial infarction, coronary revascularization, hospitalized or treated angina, and hospitalized or treated congestive heart failure

  5. Cognitive impairment [ Time Frame: At 3 months ]
    Vascular cognitive impairment measured by the MoCA

  6. Quality of life [ Time Frame: At 3 months ]
    Health-related quality of life measured by the 12-item Short Form



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03479554


Contacts
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Contact: Jiang He, MD, PhD 504-988-5165 jhe@tulane.edu
Contact: Yilong Wang, MD, PhD 01186-13911666571 yilongwang528@aliyun.com

Locations
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China, Beijing
Beijing Tiantan Hospital Recruiting
Beijing, Beijing, China, 100050
Contact: Xuewei Xie, MD, PhD    (86 10) 6709-8222    catis_2@163.com   
Sponsors and Collaborators
Tulane University
Beijing Tiantan Hospital
Soochow University
Investigators
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Principal Investigator: Jiang He, MD, PhD Tulane University
Principal Investigator: Yilong Wang, MD, PhD Beijing Tiantan Hospital
Principal Investigator: Liping Liu, MD, PhD Beijing Tiantan Hospital

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Responsible Party: Jiang He, MD, PhD, Professor and Chair of Epidemiology, Tulane University
ClinicalTrials.gov Identifier: NCT03479554     History of Changes
Other Study ID Numbers: 1109725
First Posted: March 27, 2018    Key Record Dates
Last Update Posted: September 11, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jiang He, MD, PhD, Tulane University:
antihypertensive treatment
Additional relevant MeSH terms:
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Stroke
Cerebral Infarction
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Antihypertensive Agents