China Antihypertensive Trial in Acute Ischemic Stroke (CATIS)

• ClinicalTrials.gov Identifier: NCT01840072
• Recruitment Status: Completed
• First Posted: April 25, 2013
• Results First Posted: November 20, 2014
• Last Update Posted: April 25, 2017
• Sponsor: Tulane University
• Collaborator: Soochow University
• Information provided by (Responsible Party): Jiang He, MD, PhD, Tulane University

Tracking Information

• First Submitted Date: April 13, 2013
• First Posted Date: April 25, 2013
• Results First Submitted Date: November 13, 2014
• Results First Posted Date: November 20, 2014
• Last Update Posted Date: April 25, 2017
• Study Start Date: August 2009
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 12, 2017)

A Combination of Death Within 14 Days After Randomization and Major Disability at 14 Days or at Hospital Discharge if Earlier Than 14 Days. [ Time Frame: 2 weeks ]

Major disability was defined as a score of 3 to 5 on the modified Rankin Scale at 14 days after randomization. Scores on the modified Rankin Scale range from 0 to 6, with a score of 0 indicating no symptoms; a score of 5 indicating severe disability (ie, bedridden, incontinent, or requiring constant nursing care and attention); and a score of 6 indicating death.

Original Primary Outcome Measures (submitted: April 22, 2013)

• A combined outcome of in-hospital case-fatality rate (within 2-weeks) and dependency (modified Rankin scale >2) [ Time Frame: 2 weeks ]
  The assessment using the modified Rankin scale will be obtained on 14 day after the randomization or at the hospital discharge.
• Neurological Dysfunction (NIH Stroke Scale, NIHSS) [ Time Frame: 2 weeks ]
  Neurological dysfunction assessment using NIHSS will be obtained on 14 day after the randomization or at the hospital discharge.

Current Secondary Outcome Measures (submitted: March 12, 2017)

• A Combination of All-cause Mortality and Major Disability at the 3-month Post-treatment Follow-up. [ Time Frame: 3 months ]
  Major disability was defined as a score of 3 to 5 on the modified Rankin Scale at 3 months after randomization. Scores on the modified Rankin Scale range from 0 to 6, with a score of 0 indicating no symptoms; a score of 5 indicating severe disability (ie, bedridden, incontinent, or requiring constant nursing care and attention); and a score of 6 indicating death
• Mortality [ Time Frame: 3 months ]
  Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. Information on clinical deaths will be obtained.
• Recurrent Stroke [ Time Frame: 3 months ]
  Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. Information of recurrent stroke will be collected.
• Other Vascular Events [ Time Frame: 3 months ]
  Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. Information of vascular events, such as myocardial infarction, will be collected.
• Long-term Neurological and Functional Status [ Time Frame: Three months ]
  Those patients who were still alive at hospital discharge were contacted by telephone to set up a follow-up clinical visit. Neurological function was assessed by the modified Rankin scale at the 3-month post-treatment follow-up visit. Scores on the modified Rankin Scale range from 0 to 6, with a score of 0 indicating no symptoms; a score of 5 indicating severe disability (ie, bedridden, incontinent, or requiring constant nursing care and attention); and a score of 6 indicating death. Major disability was defined as a score of 3 to 5 on the modified Rankin Scale.
• Cognitive Function (the Mini-Mental State Examination) [ Time Frame: Three months ]
  Cognitive function was measured by the Mini-Mental State Examination at 3 months after randomization. The MMSE contains 20 items that test cognitive performance in domains including orientation, registration, attention and calculation, recall, language, and visual construction. MMSE scores were divided into three ordinal categories: 24-30 (no cognitive impairment), 19-23 (mild cognitive impairment), and 0-17 (severe cognitive impairment).
• Cognitive Function (Montreal Cognitive Assessment) [ Time Frame: Three months ]
  Cognitive function was measured by Montreal Cognitive Assessment at 3 months after randomization. The MoCA is a 30-item test that evaluates the following seven cognitive domains: visuospatial/executive functions, naming, memory, attention, language, abstraction, and orientation. One point is added for participants with education <12 years. Scores on the MoCA range from 0 to 30 and cognitive impairment was defined as a score of <26.
• Quality of Life [ Time Frame: 3 months ]
  Due to limited funding, quality of life data were not collected.

Original Secondary Outcome Measures (submitted: April 22, 2013)

• Mortality [ Time Frame: 3, 12, and 24 months ]
  Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. Information on clinical deaths will be obtained.
• Recurrent Stroke [ Time Frame: 3, 12 and 24 months ]
  Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. Information of recurrent stroke will be collected.
• Other Vascular Events [ Time Frame: 3, 12 and 24 months ]
  Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. Information of vascular events, such as myocardial infarction, will be collected.
• Long-term Neurological and Functional Status [ Time Frame: 3, 12 and 24 months ]
  Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. Neurological and functional assessments including the modified Rankin scale and NIHSS will be performed.
• Cognitive Function [ Time Frame: 3, 12 and 24 months ]
  Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. The information on the cognitive function will be obtained.
• Quality of Life [ Time Frame: 3, 12 and 24 months ]
  Those patients who are still alive at hospital discharge will be contacted by telephone to set up a follow-up clinical visit. The information on the quality of life will be obtained.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: China Antihypertensive Trial in Acute Ischemic Stroke
• Official Title: Inner Mongolia Stroke Project A Randomized Controlled Trial of Immediate Blood Pressure Reduction on Death and Major Disability in Patients With Acute Ischemic Stroke in China
• Brief Summary: This randomized trial tests the effect of early blood pressure reduction on major disability and death among patients with acute ischemic stroke in china.

Detailed Description

We designed a randomized controlled clinical trial to test:

• The effectiveness of blood pressure reduction among patients with acute ischemic stroke (within 48 hours of onset) on the primary outcome, a combination of death within 14 days after randomization and dependency (modified Rankin scale ≥3) at 14 day or at the time of discharge, if that occurred before 14 days.

• The effectiveness of blood pressure reduction among patients with acute ischemic stroke (within 48-hours of onset) on secondary outcomes:

  • Combination of all-cause mortality and dependency over 3, 12, and 24 months of follow-up
  • Combined vascular disease events over 3, 12, and 24 months of follow-up (vascular deaths, non-fatal stroke, non-fatal myocardial infarction, coronary revascularization, hospitalized or treated angina, hospitalized or treated congestive heart failure, and hospitalized or treated peripheral arterial disease)
  • Recurrent fatal and non-fatal stroke over 3, 12, and 24 months of follow-up
  • Neurological functional status measured by NIH Stroke Score and modified Rankin scale at 14 day or discharge after randomization, and over 3, 12, and 24 months of follow-up
  • All-cause mortality over 3, 12, and 24 months of follow-up
  • Duration of initial hospitalization
  • Changes in systolic and diastolic blood pressure within 24 hours and over 7 days, and 14 days

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Ischemic Stroke

Intervention

Other: Active antihypertensive treatment

Initial antihypertensive treatment with angiotensin-converting enzyme inhibitors (Enalapril) and/or calcium channel blockers as second line medication; and/or diuretics as third line medications. Based on patients' baseline BP level, the first-line medication (intravenous Enalapril) can be used alone, or in combination with second-line medication (calcium channel blocker), and third-line medication (diuretics) to achieve the target systolic BP lowering by 10% to 25% within the first 24 hours after randomization and to achieve systolic BP below 140 mm Hg and diastolic BP below 90 mm Hg and maintain this BP level afterwards during the hospitalization.

Study Arms

• Experimental: Active antihypertensive treatment
  Active antihypertensive treatment
  Intervention: Other: Active antihypertensive treatment
• No Intervention: Usual care
  Discontinue all home BP medications.

Publications *

• Bu X, Li C, Zhang Y, Xu T, Wang D, Sun Y, Peng H, Xu T, Chen CS, Bazzano LA, Chen J, He J; CATIS Investigators. Early Blood Pressure Reduction in Acute Ischemic Stroke with Various Severities: A Subgroup Analysis of the CATIS Trial. Cerebrovasc Dis. 2016;42(3-4):186-95. doi: 10.1159/000444722. Epub 2016 Apr 26.
• Zhong C, Xu T, Xu T, Peng Y, Wang A, Wang J, Peng H, Li Q, Geng D, Zhang D, Zhang Y, Zhang Y, Gao X, He J; CATIS Investigation Groups. Plasma Homocysteine and Prognosis of Acute Ischemic Stroke: a Gender-Specific Analysis From CATIS Randomized Clinical Trial. Mol Neurobiol. 2017 Apr;54(3):2022-2030. doi: 10.1007/s12035-016-9799-0. Epub 2016 Feb 24.
• He J, Zhang Y, Xu T, Zhao Q, Wang D, Chen CS, Tong W, Liu C, Xu T, Ju Z, Peng Y, Peng H, Li Q, Geng D, Zhang J, Li D, Zhang F, Guo L, Sun Y, Wang X, Cui Y, Li Y, Ma D, Yang G, Gao Y, Yuan X, Bazzano LA, Chen J; CATIS Investigators. Effects of immediate blood pressure reduction on death and major disability in patients with acute ischemic stroke: the CATIS randomized clinical trial. JAMA. 2014 Feb 5;311(5):479-89. doi: 10.1001/jama.2013.282543.
• Bu X, Zhang Y, Bazzano LA, Xu T, Guo L, Wang X, Zhang J, Cui Y, Li D, Zhang F, Ju Z, Xu T, Chen CS, Chen J, He J. Effects of early blood pressure reduction on cognitive function in patients with acute ischemic stroke. Int J Stroke. 2016 Dec;11(9):1009-1019. Epub 2016 Jul 13.
• Che B, Shen S, Zhu Z, Wang A, Xu T, Peng Y, Li Q, Ju Z, Geng D, Chen J, He J, Zhang Y, Zhong C. Education Level and Long-term Mortality, Recurrent Stroke, and Cardiovascular Events in Patients With Ischemic Stroke. J Am Heart Assoc. 2020 Aug 18;9(16):e016671. doi: 10.1161/JAHA.120.016671. Epub 2020 Aug 11.
• Zhu S, Qian S, Xu T, Peng H, Dong R, Wang D, Yuan X, Guo L, Zhang Y, Geng D, Zhong C. White Matter Hyperintensity, Immediate Antihypertensive Treatment, and Functional Outcome After Acute Ischemic Stroke. Stroke. 2020 May;51(5):1608-1612. doi: 10.1161/STROKEAHA.119.028841. Epub 2020 Apr 1.
• Guo DX, Zhu ZB, Zhong CK, Bu XQ, Chen LH, Xu T, Guo LB, Zhang JT, Li D, Zhang JH, Ju Z, Chen CS, Chen J, Zhang YH, He J. Serum cystatin C levels are negatively correlated with post-stroke cognitive dysfunction. Neural Regen Res. 2020 May;15(5):922-928. doi: 10.4103/1673-5374.268928.
• Zhang R, Zhong C, Zhang Y, Xie X, Zhu Z, Wang A, Chen CS, Peng Y, Peng H, Li Q, Ju Z, Geng D, Chen J, Liu L, Wang Y, Xu T, He J. Immediate Antihypertensive Treatment for Patients With Acute Ischemic Stroke With or Without History of Hypertension: A Secondary Analysis of the CATIS Randomized Clinical Trial. JAMA Netw Open. 2019 Jul 3;2(7):e198103. doi: 10.1001/jamanetworkopen.2019.8103.
• Guo D, Zhu Z, Zhong C, Peng H, Wang A, Xu T, Peng Y, Xu T, Chen CS, Li Q, Ju Z, Geng D, Chen J, Zhang Y, He J. Increased Serum Netrin-1 Is Associated With Improved Prognosis of Ischemic Stroke. Stroke. 2019 Apr;50(4):845-852. doi: 10.1161/STROKEAHA.118.024631.
• He WJ, Zhong C, Xu T, Wang D, Sun Y, Bu X, Chen CS, Wang J, Ju Z, Li Q, Zhang J, Geng D, Zhang J, Li D, Li Y, Yuan X, Zhang Y, Kelly TN; CATIS investigators. Early antihypertensive treatment and clinical outcomes in acute ischemic stroke: subgroup analysis by baseline blood pressure. J Hypertens. 2018 Jun;36(6):1372-1381. doi: 10.1097/HJH.0000000000001690.
• Xu T, Zhang Y, Bu X, Wang D, Sun Y, Chen CS, Wang J, Peng H, Ju Z, Peng Y, Xu T, Li Q, Geng D, Zhang J, Li D, Zhang F, Guo L, Wang X, Cui Y, Li Y, Ma D, Zhang D, Yang G, Gao Y, Yuan X, Chen J, He J; CATIS investigators. Blood pressure reduction in acute ischemic stroke according to time to treatment: a subgroup analysis of the China Antihypertensive Trial in Acute Ischemic Stroke trial. J Hypertens. 2017 Jun;35(6):1244-1251. doi: 10.1097/HJH.0000000000001288.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 12, 2013): 4071
• Original Estimated Enrollment (submitted: April 22, 2013): 4000
• Actual Study Completion Date: May 2016
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≥22 years
• Ischemic stroke onset within 48 hours confirmed by imaging (CT scan or MRI) study
• Systolic BP≥140 and <220 mm Hg and diastolic BP≥80 mm Hg
• No contraindications to antihypertensive treatment
• Able and willing to sign informed consent by patients or their direct family members

Exclusion Criteria:

• Individuals with hemorrhagic stroke
• Individuals with severe heart failure (NY Heart Association class III and IV), myocardial infarction, unstable angina, aortic dissection and cerebrovascular stenosis
• Individuals in a deep coma
• Individuals with resistant hypertension [systolic BP ≥170 mm Hg despite use of 4 or more antihypertensive medications for half a year or longer]
• Intravenous thrombolytic therapy (such as intravenous rtPA)
• Individuals who are unable to participate in follow-up examination
• Current pregnant women

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 22 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT01840072
• Other Study ID Numbers: 140815
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Jiang He, MD, PhD, Tulane University
• Study Sponsor: Tulane University
• Collaborators: Soochow University

Investigators

• Principal Investigator: Jiang He, MD, PhD; Tulane University SPHTM

• PRS Account: Tulane University
• Verification Date: December 2016