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Impact of Ultra-Early Perioperative Antihypertensive Therapy in Acute Intracerebral Hemorrhage
(Ovid Technologies (Wolters Kluwer Health), 2026-06)
Tao Liu
;
Linan Chen
;
Leibo Liu
;
Yang Liu
;
Lu Ma
<jats:sec> <jats:title>BACKGROUND:</jats:title> <jats:p>Early intensive blood pressure (BP) lowering improves outcomes in acute intracerebral hemorrhage, but its perioperative benefit among patients undergoing surgical hematoma evacuation is uncertain. We evaluated whether earlier achievement of intensive BP targets is associated with improved outcomes in this population.</jats:p> </jats:sec> <jats:sec> <jats:title>METHODS:</jats:title> <jats:p>Post hoc secondary analysis of the INTERACT3 (the third Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial) pragmatic, international, multicenter, blinded-end point, and stepped-wedge cluster-randomized trial. Among 7036 enrolled intracerebral hemorrhage patients at 121 hospitals, those who underwent surgical hematoma evacuation were included. Patients were categorized by time from hospital arrival to achieving the target systolic BP <140 mm Hg: ≤2 hours versus >2 hours. The primary outcome was 6-month mortality. Key secondary outcomes included death or disability (modified Rankin Scale scores 4–6), modified Rankin Scale score shift, health-related quality-of-life (EuroQol 5-Dimension 3-Level [EQ-5D-3L] domains, visual analog scale, and health utility index), and serious adverse events. Adjusted associations were estimated using Cox, logistic, ordinal logistic, and linear regression models, controlling for age, sex, treatment type, and admission Glasgow Coma Scale.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS:</jats:title> <jats:p> Of 7036 patients with acute intracerebral hemorrhage, 1506 underwent surgical hematoma evacuation (mean [SD] age, 59.7 [11.8] years; 33.9% women). Overall, there was no statistically significant difference in 6-month mortality between patients who achieved target BP within 2 hours of treatment initiation and those who achieved it after 2 hours (adjusted hazard ratio, 0.81 [95% CI, 0.63–1.04]; <jats:italic toggle="yes">P</jats:italic> =0.09). Early BP achievement was associated with a lower risk of death or disability (adjusted odds ratio [OR], 0.71 [95% CI, 0.56–0.90]; <jats:italic toggle="yes">P</jats:italic> =0.01), a favorable shift in the distribution of modified Rankin Scale scores (adjusted common OR, 0.73 [95% CI, 0.60–0.89]; <jats:italic toggle="yes">P</jats:italic> <0.01), and fewer serious adverse events (adjusted OR, 0.73 [95% CI, 0.57–0.94]; <jats:italic toggle="yes">P</jats:italic> =0.02). EuroQol 5-Dimension 3-Level outcomes also favored the early group, with significant improvements in mobility (adjusted OR, 0.76 [95% CI, 0.60–0.97]; <jats:italic toggle="yes">P</jats:italic> =0.03), pain/discomfort (adjusted OR, 0.72 [95% CI, 0.54–0.95]; <jats:italic toggle="yes">P</jats:italic> =0.02), and usual activities (adjusted OR, 0.79 [95% CI, 0.62–1.00]; <jats:italic toggle="yes">P</jats:italic> =0.05), as well as higher visual analog scale (mean difference, 0.08 [95% CI, 0.002–0.17]; <jats:italic toggle="yes">P</jats:italic> =0.04) and health utility scores (mean difference, 0.05 [95% CI, 0.02–0.09]; <jats:italic toggle="yes">P</jats:italic> <0.01). </jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS:</jats:title> <jats:p>In patients with intracerebral hemorrhage undergoing surgical hematoma evacuation, perioperative intensive BP reduction appears safe. Achieving systolic BP <140 mm Hg within 2 hours was associated with better functional and quality-of-life outcomes, and fewer serious adverse events. These time-sensitive associations support prioritizing ultra-early perioperative BP control; confirmatory prospective analyses are warranted.</jats:p> </jats:sec> <jats:sec> <jats:title>REGISTRATION:</jats:title> <jats:p> URL: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.clinicaltrials.gov">https://www.clinicaltrials.gov</jats:ext-link> ; Unique identifier: NCT03209258. </jats:p> </jats:sec>
1
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Sex differences in the clinical and surgical management after intracerebral hemorrhage: A post hoc analysis of the INTERACT3 clinical trial
(SAGE Publications, 2026-02-05)
Ma. Ignacia Allende
;
Cheryl Carcel
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MUÑOZ VENTURELLI, PAULA ANDREA
;
Katie Harris
;
Menglu Ouyang
<jats:sec> <jats:title>Introduction:</jats:title> <jats:p>As the management of intracerebral hemorrhage (ICH) shifts from historical inertia to more proactive, evidence-based care, ensuring sex-equitable access to best-practice stroke care is increasingly important. Data on sex differences in access to care for ICH remains limited and often conflicting. More robust evidence is required to understand where disparities may exist to inform targeted interventions.</jats:p> </jats:sec> <jats:sec> <jats:title>Aims:</jats:title> <jats:p>We aimed to determine sex differences in the clinical and surgical management of patients with acute ICH who participated in the third Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>We performed a post hoc analysis of INTERACT3, an international stepped-wedge, cluster-randomised trial undertaken in 121 hospitals across 9 low- to middle-income countries and 1 high-income country. The trial aimed to evaluate a care bundle composed of intensive blood-pressure lowering, rapid correction of hyperglycemia, fever control, and reversal of anticoagulation; in adults presenting within 6 h of ICH onset. We used mixed-effects logistic regression to evaluate sex differences in access to surgical interventions, admission to an intensive care unit or acute stroke unit, assisted feeding, physiotherapy, occupational therapy, withdrawal of care, and use of pharmacological therapies (antiepileptic drugs, mannitol, dexamethasone, and statins). Patterns of care were further evaluated using latent class analysis, with sex differences analyzed using the same regression framework.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>Of 7036 patients with ICH, 2533 (36%) were female. Females were older and had more severe neurological deficits. Overall care provision was similar across sexes. However, females were more likely to receive assisted feeding (odds ratio [OR] 1.15, 95% CI = 1.02–1.31), and were less likely to withdraw from active care (OR 0.41, 95% CI = 0.19–0.87) than males. Surgical interventions were accessed at similar rates among sexes, a finding that persisted in analyses restricted to supratentorial ICH with hematoma volumes ⩾ 30 mL. Three distinct care classes were identified: high-intensity, high-rehabilitation, and low-intensity, with females and males having comparable distributions within the classes.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>Following acute ICH, females generally receive similar active acute care interventions as males, except for observed differences in access to assisted feeding and decision to withdraw from active care. These findings suggest that equal access to ICH interventions for females and males is feasible and exists in some settings. However, disparities in certain key interventions remain and present actionable opportunities for improvement. Further research is needed to explore not only access but also the timing and frequency of these interventions.</jats:p> </jats:sec> <jats:sec> <jats:title>Data access statement:</jats:title> <jats:p>Individual, de-identified participant data used in these analyses will be shared on request from any qualified investigator after the approval of a protocol and signed data access agreement via both the trial steering committee and the research office of The George Institute for Global Health (Sydney, NSW, Australia).</jats:p> </jats:sec>
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Mediation Analysis to Identify Individual Component Effects of the Care Bundle to Improve Functional Outcome After ICH in the INTERACT3 Study
(Ovid Technologies (Wolters Kluwer Health), 2025-10)
Xinwen Ren
;
Qiang Li
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Menglu Ouyang
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Laurent Billot
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Xiaoying Chen
1Scopus© Citations 6
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Surgical outcomes from haematoma evacuation for intracerebral haemorrhage in the INTERACT3 study
(Elsevier BV, 2025-09)
Xin Hu
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Menglu Ouyang
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Jianguo Xu
;
Yi Liu
;
Xi Li
1Scopus© Citations 4
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Risk and impact of stroke across 38 countries and territories of the Americas from 1990 to 2021: a population-based trends analysis from the Global Burden of Disease Study 2021
(Elsevier BV, 2025-03)
Ramón Martinez
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MUÑOZ VENTURELLI, PAULA ANDREA
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Pedro Ordunez
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Felipe Fregni
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Carlos Abanto
Scopus© Citations 22 3
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Implementation of a goal-directed Care Bundle for intracerebral hemorrhage: Results of embedded process evaluation in the INTERACT3 trial
(Public Library of Science (PLoS), 2024-12-19)
Menglu Ouyang
;
Anila Anjum
;
Francisca Gonzalez Mc Cawley
;
Mohammad Wasay
;
Lu Ma
<jats:p>The third, stepped-wedge, cluster-randomized, Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3), has shown that a goal-directed multi-faceted Care Bundle incorporating protocols for the management of physiological variables was safe and effective for improving functional recovery in a broad range of patients with acute intracerebral hemorrhage (ICH). The INTERACT3 Care Bundle included time- and target-based protocols for the management of early intensive lowering of systolic blood pressure (SBP, target <140mmHg), glucose control (target 6.1–7.8 mmol/L in those without diabetes and 7.8–10.0 mmol/L in those with diabetes), anti-pyrexia treatment (target body temperature ≤37.5°C), and the rapid reversal of warfarin-related anticoagulation (target international normalized ratio <1.5). An embedded process evaluation was conducted to allow a better understanding of how the Care Bundle was implemented in different countries to enhance the transferability of this evidence in the international context. This study used a mixed-methods approach involving interviews, focus group discussions, and surveys to evaluate the implementation outcomes included fidelity, dose, reach, acceptability, appropriateness, adoption, and sustainability. Interviews (n = 27), focus group discussions (n = 3), and quantitative surveys (n = 48) were conducted in 7 low- and middle-income countries (LMICs) and 1 high-income country during 2019–2022. The Care Bundle was generally delivered as planned and well accepted by stakeholders, although some difficulties were reported in reaching the SBP and glycemic targets. Contextual factors including staff shortage, limited availability of antihypertensive drugs, and delayed systems of care processes, were common barriers to implementing the Care Bundle. Facilitating factors included good communication and collaboration with staff in emergency departments, the development of pathways within available resources, and regular training and monitoring. Our process evaluation provides useful insights into the contextual barriers which need to be addressed for effective scale up of the Care Bundle implementation in a global context.</jats:p> <jats:p><jats:bold>Trial registration</jats:bold>: INTERACT3 is registered at Clinicaltrials.gov (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT03209258" xlink:type="simple">NCT03209258</jats:ext-link>) and the Chinese Clinical Trial Registry (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.chictr.org.cn/showprojEN.html?proj=19647" xlink:type="simple">ChiCTR-IOC-17011787</jats:ext-link>).</jats:p>
2Scopus© Citations 3
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Predictive Accuracy of Clinicians Estimates of Death and Recovery after Acute Intracerebral Hemorrhage: Pre-Specified Analysis in INTERACT3 Study
(2024)
Menglu Ouyang
;
Lu Ma
;
Xiaoying Chen
;
Xia Wang
;
Laurent Billot
<jats:p>Introduction: Accurately predicting a patient’s prognosis is an important component of decision-making in intracerebral hemorrhage (ICH). We aimed to determine clinicians’ ability to predict survival, functional recovery, and return to premorbid activities in patients with ICH. Methods: Pre-specified secondary analysis of the third intensive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3), an international, multicenter, stepped-wedge cluster randomized controlled trial. Clinician perspectives on prognosis were collected at hospital admission and Day 7 (or before discharge). Prognosis questions were the likelihood of (i) survival at 48 h and 6 months, (ii) favorable functional outcome (recovery walking and self-care), and (iii) return to usual activities at 6 months. Clinician predictions were compared with actual outcomes. Results: Most clinician participants were from neurosurgery (75%) with a median of 8 working years (IQR 5–14) of experience. Of the 6,305 randomized patients who survived 48 h, 213 (3.4%) were predicted to die (positive predictive value [PPV] 0.99, 95% confidence interval [CI] 0.99–0.99). Of 5,435 patients who survived 6 months, 209 (3.8%) were predicted to die (PPV 0.93, 95% CI: 0.92–0.93). Predictions on the favorable functional outcome (PPV 0.54, 95% CI: 0.52–0.56) and satisfied ability to return to usual activities (PPV 0.50, 95% CI: 0.49–0.52) were poor. Prediction accuracy varied by working years and region of practice. Conclusions: In patients with ICH, clinician estimates of death are very good but conversely they are poor in predicting higher levels of functional recovery and activities. </jats:p>
1
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Availability and barriers to access post-stroke rehabilitation in Latin America
(2024)
Alejandro Gonzalez-Aquines
;
Julieta Rosales
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Ana Claudia De Souza
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Angel Corredor-Quintero
;
Miguel A. Barboza
Scopus© Citations 1 3
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Abstract P84: Covid-19 and Stroke in the Latin American Stroke Registry (LASE)
(2021)
Virginia Pujol-Lereis
;
Alan F Flores
;
Antonio Arauz
;
Carlos Abanto
;
Pablo Amaya
<jats:p> <jats:bold>Background:</jats:bold> Ischemic stroke has been reported to occur in approximately 5% of COVID-19 patients, although some reports are contradictory. Proposed mechanisms of this association are hypercoagulable state, vasculitis and cardiomyopathy, together with traditional vascular risk factors. We analyzed the frequency and clinical characteristics of COVID-19 positive stroke cases during the first months of the pandemic in Latin America. </jats:p> <jats:p> <jats:bold>Methods:</jats:bold> A multinational study (7 countries, 18 centers) of patients admitted during the pandemic outbreak (March - June 2020). We assessed acute stroke cases associated to COVID-19 infection. Clinical characteristics, stroke etiology and severity, acute care and functional outcomes, were compared between non-COVID-19 and COVID-19 cases. </jats:p> <jats:p> <jats:bold>Results:</jats:bold> There were a total of 1037 stroke cases; sixty-two of them (6.0%) were diagnosed with COVID-19 infection. This group consisted of 38 men [61.3%], with a median age of 68 years [IQR 59-79 years]. From these cases, 80.6% were ischemic stroke, 16.1% hemorrhagic stroke, and 1.6% transient ischemic attack and cerebral venous thrombosis respectively. The most common etiology reported for ischemic cases was atherosclerotic large vessel occlusion (30.6% vs. 12.7% in non-COVID cases, p<0.001), and undetermined etiology for hemorrhagic stroke (55.6%). Median NIHSS for COVID-stroke patients was higher (7 IQR 2-16 vs. 5 IQR 2-11, p=0.05). Five (8.1%) patients received acute reperfusion therapy, with no differences in door-to-CT, door-to-needle and door-to-groin times, compared to non-COVID cases. Most characteristics did not differ from those of COVID-19 negative patients. Mortality was higher in COVID-stroke cases (20.9% vs. 9.6%, p<0.001). </jats:p> <jats:p> <jats:bold>Conclusions:</jats:bold> COVID-19 infection frequency in stroke patients in Latin America is similar to that reported in several series worldwide, with a higher frequency of atherosclerotic ischemic strokes and mortality compared to non COVID-19 strokes </jats:p>
2
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The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial
(2023)
Lu Ma
;
Xin Hu
;
Lili Song
;
Xiaoying Chen
;
Menglu Ouyang
Scopus© Citations 221 1

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