China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2): rationale and design.
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ABSTRACT: Backgrounds
Increased blood pressure (BP) for patients who had an acute ischaemic stroke is associated with poor functional outcome, however the optimal timing of antihypertensive therapy is unknown.Aims
We aim to compare early antihypertensive treatment to delayed antihypertensive treatment for reducing the risk of composite major disability and mortality at 3 months in acute ischaemic stroke.Design
The China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) trial is a multicentre, randomised, open-label, blinded-endpoints trial that will be conducted in 100 hospitals in China. The primary outcome is the composite of death and major disability (modified Rankin Scale score ≥3) at 3 months of randomisation. Antihypertensive treatment will be received immediately after randomisation in the early treatment group, aimed at average systolic BP by 10%-20% reduction within the first 24 hours, and achieving an average BP level of <140/90 mm Hg within 5 days. Patients in the delayed treatment group will discontinue any antihypertension medications for the first 7 days of randomisation, and will receive antihypertensive therapy achieving a BP goal of <140/90 mm Hg after 7 days.Conclusion
The CATIS-2 trial will be testing the hypotheses that early BP lowering leads to improved functional outcome without any other harms, and developing clinical guidelines of the BP management for patients who had an acute ischaemic stroke.Trial registration number
NCT03479554.
SUBMITTER: Liu L
PROVIDER: S-EPMC8258043 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The optimal time to initiate antihypertensive therapy among patients with acute ischemic stroke remains uncertain. We tested the effects of blood pressure reduction among patients with acute ischemic stroke according to time from onset to initiation of antihypertensive treatment.We randomly assigned 4071 acute ischemic stroke patients with elevated SBP to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. The primary outcome was a combination of death and major disability, and secondary outcomes included the modified Rankin score, recurrent stroke, vascular disease events, and all-cause mortality.At 24?h after randomization, the differences in SBP reductions were 8.7, 9.5, and 9.6?mmHg between the antihypertensive treatment and control groups among patients receiving treatment within less than 12, 12-23, and 24-48?h after stroke onset, respectively (P?<?0.001 in all subgroups). At day 14 or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups in all subgroups. At the 3-month follow-up, death or major disability [odds ratio (OR) 0.73; 95% confidence interval (CI) 0.55-0.96; P?=?0.03], recurrent stroke (OR 0.25; 95% CI 0.08-0.74; P?=?0.01), and vascular events (OR 0.41; 95% CI 0.18-0.95; P?=?0.04) were significantly reduced in the antihypertensive treatment group only among participants who received treatment between 24 and 48?h.Blood pressure reduction might reduce 3-month death and major disability and recurrent stroke among patients with acute ischemic stroke who receive antihypertensive treatment between 24 and 48?h after stroke onset.ClinicalTrials.gov Identifier: NCT01840072.
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Project description:ImportanceClinical trials have generally shown a neutral effect of early blood pressure (BP) decreases on clinical outcomes after acute ischemic stroke. Whether the effect of early antihypertensive therapy differs for patients with ischemic stroke with or without prior hypertension is unclear.ObjectiveTo investigate the association between immediate antihypertensive treatment and patient outcomes according to the presence or absence of hypertension before stroke onset.Design, setting, and participantsThis study was a prespecified subgroup analysis of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS), a multicenter, single-blind, blinded end-points randomized clinical trial of 4071 patients with acute ischemic stroke and elevated systolic BP. Patients were recruited from August 2009 to May 2013, and this statistical analysis was performed using the intention-to-treat population from January to October 2018.InterventionsParticipants were randomly assigned to receive antihypertensive treatment (aimed at decreasing systolic BP by 10%-25% within the first 24 hours after randomization, achieving systolic BP <140 mm Hg and diastolic BP <90 mm Hg within 7 days, and maintaining this level during hospitalization) or to the control arm (discontinued all antihypertensive medications).Main outcomes and measuresPrimary outcome was a combination of death and major disability (modified Rankin Scale score ≥3; range 0-6, with higher values indicating greater disability) at 14 days or hospital discharge.ResultsIn total, 2038 patients were randomized to receive antihypertensive treatment, and 2033 patients were randomized to the control group. The mean (SD) age was 62.0 (10.9) years, and 2604 participants (64.0%) were men. At day 14 or hospital discharge, the primary outcome was not different between the treatment and control groups among patients with or without prior hypertension (P = .97 for homogeneity): odds ratios (ORs) associated with treatment were 1.00 (95% CI, 0.87-1.16) for patients with prior hypertension and 1.00 (95% CI, 0.75-1.32) for patients without. Early antihypertensive treatment was associated with different rates of 3-month recurrent stroke (patients with hypertension: OR, 0.44; 95% CI, 0.25-0.77 vs without hypertension: OR, 3.43; 95% CI, 0.94-12.55; P = .005 for homogeneity) and vascular events (patients with hypertension: OR, 0.66; 95% CI, 0.43-1.02 vs those without hypertension: OR, 1.91; 95% CI, 0.75-4.83; P = .04 for homogeneity) by hypertension history.Conclusions and relevanceAmong patients with acute ischemic stroke, early antihypertensive treatment was not associated with different death and major disability outcomes by hypertension history. However, early antihypertension therapy was associated with a decreased rate of recurrent stroke among patients with a history of hypertension and may inform future studies in the optimal approach to hypertension management in the setting of acute ischemic stroke.Trial registrationClinicalTrials.gov identifier: NCT01840072.
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Project description:The relationship between serum uric acid (UA) and outcomes after acute ischemic stroke remains debatable in human studies, and the sex effect on this association has yet to be explored. Here, we investigated these associations in a prospective study from the China Antihypertensive Trial in Acute Ischemic Stroke. Baseline UA levels were measured in 3284 acute ischemic stroke patients. Primary outcome was defined as a combination of death and major disability (modified Rankin Scale score ?3) at 3 months. UA levels were significantly higher in men than women (310.6?±?96.1 vs 257.5?±?89.9??mol/L, P?<?0.001). The association between serum UA and the primary outcome was appreciably modified by sex (P-interaction?=?0.007). After multivariate adjustment, a high serum UA was associated with a decreased risk of primary outcome in men [odds ratio (OR), 0.63; 95% confidence interval (CI), 0.44-0.91; P-trend?=?0.01] but not in women (OR, 1.29; 95% CI, 0.83-2.01; P-trend?=?0.15), when two extreme quartiles were compared. Subgroup and sensitivity analyses further confirmed these sex-specific findings. Our study indicated that there was a sex-specific association between serum UA and prognosis of acute ischemic stroke. Elevated serum UA was positively associated with better prognosis in men, but not in women.
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Project description:BackgroundClinical trials have generally showed a neutral effect of blood pressure (BP) reduction on clinical outcomes among acute ischemic stroke patients. We conducted a prespecified subgroup analysis to assess whether disease severity modifies the effect of early antihypertensive treatment on death and disability among patients with acute ischemic stroke.MethodsIn the China Antihypertensive Trial in Acute Ischemic Stroke, 4,071 patients with acute ischemic stroke and elevated BP were randomly assigned to receive antihypertensive treatment or to discontinue all hypertension medications within 48 h of symptom onset. The primary outcome was a combination of death and major disability at 14 days or hospital discharge. In this subgroup analysis, participants were categorized into 3 groups according to their baseline NIH Stroke Scale (NIHSS) scores (0-4, 5-15, or ≥16).ResultsAt 24 h after randomization, mean systolic BP differences (95% CIs) were -8.5 (-10.0 to -7.1), -9.8 (-11.4 to -8.3), and -9.1 (-14.4 to -3.8) mm Hg between the treatment and control groups (all p values <0.001) for patients with a baseline NIHSS score of 0-4, 5-15, and ≥16, respectively. At day 7 after randomization, the corresponding mean systolic BP differences were -9.3 (-10.5 to -8.2), -9.1 (-10.3 to -7.8), and -10.1 (-15.1 to -5.1) mm Hg between the treatment and control groups (all p values <0.001). The primary outcome was not significantly different between the treatment and control groups at day 14 or hospital discharge among all NIHSS subgroups (p value for homogeneity = 0.66). ORs (95% CI) associated with treatment were 1.14 (0.87-1.49, p = 0.33), 1.04 (0.86-1.25, p = 0.70), and 0.67 (0.18-2.44, p = 0.54) for patients with a baseline NIHSS score of 0-4, 5-15, and ≥16, respectively. The composite outcome of death and major disability at 3-month follow-up did not differ between the 2 comparison groups for all NIHSS subgroups. In addition, vascular events and recurrent stroke were not significantly different between the 2 comparison groups at the 3-month follow-up visit among all NIHSS subgroups except that there was a suggestive risk reduction for recurrent stroke among those with an NIHSS score of 5-15 (OR 0.45, 95% CI 0.20-0.99, p = 0.05).ConclusionEarly BP reduction with antihypertensive medications did not reduce or increase the risk of death, major disabilities, recurrent instances of stroke, and vascular events in acute ischemic stroke patients with a variety of disease severities.
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Project description:Randomized, double-blinded, placebo-controlled trials have significant impact on clinical practice. The ultimate goal of a clinical trial of therapy for acute ischemic stroke (AIS) is to compare 2 interventions. Challenges may include interventional therapy standardization, enrollment rate, patient selection, biases, data and safety monitoring, reporting, and financial and logistical support.Selected randomized and single-arm prospective AIS trial designs. Clinical trial elements and their challenges are reviewed. Innovative designs and proposed recommendations to overcome some of the specific challenges and limitations are discussed.AIS therapy trials have specific challenges related to ethical issues, enrollment rate, outcome measures, limited time to treatment, efficacy, safety, and limited or variable operator experience with complex technology in a delicate end organ. Proposed suggestions for improving trial design include the following: incorporation of a lead-in phase; careful patient and outcome measure selection; historical, concurrent, or hybrid controls; open data access; and a Bayesian approach. An open data paradigm may facilitate creation of computerized prediction models for future trials (minimizing cost by decreasing sample size or providing futility analyses and directing resources to other trials). Collaborative, consortium, and network infrastructures may allow more effective and efficient study completion. Self-learning, self-correcting trials with intrinsic flexibility to adapt may help future clinical trial design in AIS.The randomized clinical trial design in AIS endovascular therapy is challenging. Lead-in phases, careful patient selection, use of innovative outcome measures, control groups, and newer clinical trial design may enhance conduct of future trials, their validity, and their results.
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Project description:BACKGROUND:Ischemic stroke and other vascular outcomes occur in 10-20% of patients in the three-months following a transient ischemic attack or minor ischemic stroke, and many are disabling. The highest risk period for these outcomes is the early hours and days immediately following the ischemic event. Aspirin is the most common antithrombotic treatment used for these patients. AIM:The aim of POINT is to determine whether clopidogrel plus aspirin taken <12?h after transient ischemic attack or minor ischemic stroke symptom onset is more effective in preventing major ischemic vascular events at 90 days in the high-risk, and acceptably safe, compared with aspirin alone. DESIGN:POINT is a prospective, randomized, double-blind, multicenter trial in patients with transient ischemic attack or minor ischemic stroke. Subjects are randomized to clopidogrel (600?mg loading dose followed by 75?mg/day) or matching placebo, and all will receive open-label aspirin 50-325?mg/day, with a dose of 162?mg daily for five-days followed by 81?mg daily strongly recommended. STUDY OUTCOMES:The primary efficacy outcome is the composite of new ischemic vascular events - ischemic stroke, myocardial infarction, or ischemic vascular death - by 90 days. The primary safety outcome is major hemorrhage, which includes symptomatic intracranial hemorrhage. DISCUSSION:Aspirin is the most common antithrombotic given to patients with a stroke or transient ischemic attack, as it reduces the risk of subsequent stroke. This trial expects to determine whether more aggressive antithrombotic therapy with clopidogrel plus aspirin, initiated acutely, is more effective than aspirin alone.
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Project description:BackgroundOur recent pilot study suggests intra-arterial tenecteplase (TNK) during the first pass of endovascular treatment (EVT) seems safe, may increase first-pass reperfusion and good outcome in acute ischaemic stroke (AIS) patients with large-vessel occlusion (LVO).AimsTo determine the efficacy and safety of intra-arterial TNK administration during EVT in AIS-LVO patients presenting up to 24 hours from symptom onset.Sample size estimatesA maximum of 380 patients are required to test the superiority hypothesis with 80% power according to a two-side 0.05 level of significance, stratified by age, gender, baseline systolic blood pressure, prestroke modified Rankin Scale (mRS), baseline National Institute of Health stroke scale, baseline ASPECTS, time from onset to groin puncture, intravenous thrombolysis before EVT, stroke territory and stroke aetiology.DesignIntra-arterial TNK during thrombectomy for acute stroke (BRETIS-TNK II) study is a prospective, randomised, adaptive enrichment, open-label, blinded end point, multicentre study. Eligible AIS-LVO patients are randomly assigned into the experimental group and control group with a ratio of 1:1. The experimental group will be treated with intra-arterial infusion of TNK during EVT. The control group will be treated with standard EVT.OutcomeThe primary end point is a favourable outcome, defined as an mRS score of 0-2 at 90 days. The primary safety end point is symptomatic intracranial haemorrhage within 48 hours, which is defined as an increase in the National Institutes of Health Stroke Scale score of ≥4 points as a result of the intracranial haemorrhage.ConclusionsThe results of BRETIS-TNK II will provide evidence for the efficacy and safety of intra-arterial TNK administration during EVT in AIS patients with LVO.
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