Clinical trial NCT01840072: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ischemic Stroke
Keywords: Ischemic stroke
Hypertension
Antihypertensive Agents
Randomized Controlled Trial
Lead sponsor: Tulane University
Sponsor class: OTHER
Collaborators: name: Soochow University
First posted: 2013-04-25
Enrollment: 4071
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: A Combination of Death Within 14 Days After Randomization and Major Disability at 14 Days or at Hospital Discharge if Earlier Than 14 Days.
timeFrame: 2 weeks
Secondary outcomes:
measure: A Combination of All-cause Mortality and Major Disability at the 3-month Post-treatment Follow-up.
timeFrame: 3 months
measure: Mortality
timeFrame: 3 months
measure: Recurrent Stroke
timeFrame: 3 months
measure: Other Vascular Events
timeFrame: 3 months
measure: Long-term Neurological and Functional Status
timeFrame: Three months
measure: Cognitive Function (the Mini-Mental State Examination)
timeFrame: Three months
measure: Cognitive Function (Montreal Cognitive Assessment)
timeFrame: Three months
measure: Quality of Life
timeFrame: 3 months
Other outcomes:
Locations:
city: Suzhou
country: China
facility: Soohow University
state: Jiangsu
Study officials:
affiliation: Tulane University SPHTM
name: Jiang He, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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. doi: 10.1177/1747493016660094. Epub 2016 Jul 13.
citation: Zhai Y, Che B, Liu Y, Peng H, Wang A, Peng Y, Chen J, Zhang Y, Xu T, Zhong C, He J. Effect of Immediate Antihypertensive Treatment on Clinical Outcomes in Acute Ischemic Stroke Patients With Different Renal Function Status. Hypertension. 2023 Jan;80(1):204-213. doi: 10.1161/HYPERTENSIONAHA.122.20202. Epub 2022 Nov 10.
citation: Du J, Miao M, Lu Z, Chen H, Bao A, Che B, Zhang J, Ju Z, Xu T, He J, Zhang Y, Zhong C. Plasma l-carnitine and risks of cardiovascular events and recurrent stroke after ischemic stroke: A nested case-control study. Nutr Metab Cardiovasc Dis. 2022 Nov;32(11):2579-2587. doi: 10.1016/j.numecd.2022.08.016. Epub 2022 Aug 28.
citation: Xu T, Zhang K, Zhong C, Zhu Z, Zheng X, Yang P, Che B, Lu Y, Zhang Y. Plasma Human Cartilage Glycoprotein-39 Is Associated With the Prognosis of Acute Ischemic Stroke. J Am Heart Assoc. 2022 Sep 20;11(18):e026263. doi: 10.1161/JAHA.122.026263. Epub 2022 Sep 14.
citation: Zang Y, Zhu Z, Shi M, Wang A, Xie X, Xu T, Peng Y, Yang P, Li Q, Ju Z, Geng D, Chen J, Liu L, Zhang Y, He J. Association between annual household income and adverse outcomes in patients who had ischaemic stroke. J Epidemiol Community Health. 2022 Mar;76(3):293-300. doi: 10.1136/jech-2021-216481. Epub 2021 Sep 7.
citation: Zhong C, Miao M, Che B, Du J, Wang A, Peng H, Bu X, Zhang J, Ju Z, Xu T, He J, Zhang Y. Plasma choline and betaine and risks of cardiovascular events and recurrent stroke after ischemic stroke. Am J Clin Nutr. 2021 Oct 4;114(4):1351-1359. doi: 10.1093/ajcn/nqab199.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.