BALANCE Trial Domain Within the ACT-GLOBAL Adaptive Platform Trial-NCT06352632

Hypertension is the most common physiological abnormality in patients presenting with acute ischemic stroke (AIS), and elevated blood pressure (BP) plays a critical role in determining eligibility and timing for intravenous thrombolysis.

Current international guidelines recommend lowering BP to below 185/110 mmHg before administering thrombolytic therapy, a process that requires antihypertensive treatment and inevitably delays thrombolysis. However, this recommendation lacks robust evidence. Meanwhile, because the effectiveness of thrombolysis is highly time-dependent, these BP-lowering delays may worsen clinical outcomes by prolonging door-to-needle time and delaying reperfusion.

On the other hand, recent prospective studies on blood pressure management before and after thrombolysis and thrombectomy have shown that lower BP levels do not significantly reduce the risk of hemorrhage and may lead to poorer long-term outcomes. Although these studies compared BP ranges below 180 or 185 mmHg, it remains unclear whether this pattern applies to patients with severely elevated BP. These findings suggest the importance of avoiding large and rapid BP fluctuations. Initiating thrombolysis after BP reduction could result in significant BP fluctuations and prolonged periods of low BP post-thrombolysis.

Given the lack of high-quality evidence on optimal treatment strategies for patients with pre-thrombolysis hypertension, an alternative concurrent BP management strategy has been proposed. This approach involves initiating thrombolysis and antihypertensive treatment simultaneously. By doing so, it aims to minimize treatment delays while maintaining BP control within accepted post-thrombolysis targets. However, concerns exist about whether initiating thrombolysis at higher-than-recommended BP levels increases the risk of symptomatic intracerebral hemorrhage or other complications. Consequently, substantial clinical uncertainty exists regarding which strategy-concurrent or sequential BP management-is superior for patients.

The BALANCE trial is a prospective, multicenter, randomized controlled study compare the effectiveness and safety between concurrent and sequential strategies. The concurrent strategy involves immediate initiation of intravenous thrombolysis, accompanied by simultaneous IV antihypertensive therapy to gradually lower BP during and after thrombolysis. In contrast, the sequential strategy starts with antihypertensive treatment, and thrombolysis is withheld until BP falls within guideline-recommended limits. AIS patients presenting within 4.5 hours of symptom onset with pre-thrombolysis BP exceeding guideline-recommended ranges (e.g., China: 180/100 mmHg; U.S./Canada/Europe: 185/110 mmHg) but below 220 mmHg, and who are otherwise eligible for intravenous thrombolysis, will be enrolled across 80-100 stroke centers worldwide. The primary endpoint is a hierarchical composite outcome analyzed using the win ratio method. It comprises three components, prioritized in the following order: (1) functional outcome, defined as the distribution of modified Rankin Scale (mRS) scores at 90 days after randomization; (2) major safety, defined as the occurrence of symptomatic intracerebral hemorrhage (sICH) within 7 days after randomization according to the SITS-MOST criteria; and (3) process efficiency, defined as door-to-needle time (DNT)-the interval from emergency department arrival to the start of thrombolytic infusion. In pairwise comparisons between treatment groups, a patient "wins" if they have a better outcome on the highest-priority component where a difference exists.

By evaluating these two fundamentally different management pathways, the BALANCE trial seeks to generate definitive evidence that may inform future guideline recommendations and optimize care for patients with acute ischemic stroke and elevated blood pressure.

• Excellent Functional Outcome [Срок оценки: 90-day]
• Good Functional Outcome [Срок оценки: 90-day]
• Distribution of Functional Outcome [Срок оценки: 90-day]
• Quality of Life at 90 days [Срок оценки: 90-day]
• Neurological Status at 72 Hours [Срок оценки: 72±12 hours]
• Early Neurological Improvement [Срок оценки: 72±12 hour]
• Mortality [Срок оценки: 90-day]
• Malignant Cerebral Edema [Срок оценки: 90-day]
• Process Metrics [Срок оценки: 24-hour]