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

NCT07318948 | Not Yet Recruiting DMC

• 1 other identifier: 2025(No.2280)
• Study Type: interventional
• Target: 1,600
• Locations: 1 country
• Sites: 1

Brief Summary

Elevated blood pressure (BP) is nearly universal in acute ischemic stroke (AIS) and critically influences eligibility for intravenous thrombolysis; however, current guidelines-requiring BP reduction to below 185/110 mmHg before treatment-lack robust evidence and may delay reperfusion in a time-sensitive therapy, potentially worsening outcomes. Emerging data suggest that aggressive pre-thrombolysis BP lowering does not reduce hemorrhage risk and might impair recovery, highlighting the need to avoid large BP fluctuations. Yet it remains uncertain whether initiating thrombolysis concurrently with antihypertensive therapy is safer and more effective than the standard sequential approach, particularly in patients with markedly elevated but not extreme BP (systolic \<220 mmHg). To address this gap, the BALANCE trial is a prospective, multicenter, randomized controlled study enrolling AIS patients within 4.5 hours of onset whose pre-thrombolysis BP exceeds regional guideline thresholds (e.g., \>180/100 mmHg in China or \>185/110 mmHg internationally) but is \<220 mmHg and who are otherwise eligible for thrombolysis. Patients are randomized to either: (1) concurrent management-immediate thrombolysis with simultaneous IV antihypertensive therapy to gradually lower BP-or (2) sequential management-antihypertensive treatment first, followed by thrombolysis only after BP reaches target. The primary endpoint is a hierarchical composite analyzed using the win ratio, prioritizing: (1) functional outcome (90-day mRS distribution), (2) major safety (symptomatic intracerebral hemorrhage within 7 days per SITS-MOST criteria), and (3) process efficiency (door-to-needle time). Conducted across 80-100 global stroke centers, BALANCE aims to provide definitive evidence to optimize BP management and improve outcomes in AIS patients with elevated BP.

Conditions

Acute Ischemic Stroke

Keywords

Acute Ischemic Stroke; Thrombolysis; Blood Management

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint: A Justification for the Hierarchical Win Ratio

  The win ratio is a patient-centered statistical method that allows for the comparison of treatment arms across several prioritized outcomes. It provides a more holistic assessment of the net clinical benefit. The hierarchy is ordered based on clinical importance: 1. Functional Outcome: Defined as the distribution in scores on the modified Rankin scale (mRS) at 90 days after randomization. 2. Major Safety: Defined as the sICH occurrence within 7 days after randomization, based on SITS-MOST criteria. Process Efficiency: Defined as the time between emergency department entry to thrombolysis start (DNT).

  90-day

Secondary Outcomes (9)

• Excellent Functional Outcome

  90-day

• Good Functional Outcome

  90-day

• Distribution of Functional Outcome

  90-day

• Quality of Life at 90 days

  90-day

• Neurological Status at 72 Hours

  72±12 hours

Other Outcomes (5)

• sICH occurrence

  7-day

• Any Intracerebral Hemorrhage

  7-day

• Hemorrhagic Event Classification

  7-day

Study Arms (2)

Sequential Arm

NO INTERVENTION

1. Antihypertensive Therapy: Immediately after randomization, intravenous antihypertensive therapy is initiated to actively lower the patient's blood pressure to below the guideline recommended range. 2. Thrombolysis: Once the blood pressure is confirmed to be at or below the guideline recommended range, intravenous thrombolysis (alteplase or tenecteplase, per local standard of care) is administered.

Conccurent Arm

EXPERIMENTAL

1. Thrombolysis: Immediately after randomization, intravenous thrombolysis (alteplase or tenecteplase, per local standard of care) is administered as per local practice. 2. Antihypertensive Therapy: As soon as feasible after the start of thrombolysis, intravenous antihypertensive therapy is initiated with the goal of lowering blood pressure to below guideline recommended range. (e.g. China: 180/100 mmHg; U.S./Canada/Europe: 185/110 mmHg).

Other: Concurrent Thrombolysis

Interventions

Concurrent Thrombolysis OTHER

Lowering the blood pressure and undergoing thrombolysis at the same time while the partipants blood pressure is higher than 185/110 mmHg or 180/100 mmHg.

Conccurent Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• Clinical diagnosis of acute ischemic stroke with a clearly defined time of symptom onset or last known well, allowing for randomization within 4.5 hours.
• The treating physician has made the decision to treat the patient with intravenous thrombolysis.
• Elevated blood pressure, defined as: Pre-thrombolysis BP exceeds guideline-recommended range (e.g. China: 180/100 mmHg; U.S./Canada/Europe: 185/110 mmHg), but below 220 mmHg.
• \*The qualifying blood pressure must be confirmed by two separate measurements taken at least one minute apart from the same arm, using an appropriately sized cuff while the patient is in a supine or semi-recumbent position.
• Informed consent is obtained from the patient or a legally authorized representative in accordance with local regulations. A deferred or waiver of consent model will be used where permitted by local ethics committees for emergency research.

You may not qualify if:

• Any condition that, in the judgment of the investigator, would preclude follow-up or interfere with outcome assessment (e.g., end-stage malignancy, severe multi-organ failure).
• The patient is pregnant or breastfeeding.
• Concurrent enrollment in another interventional trial where the intervention is likely to confound the study endpoints.

Sponsors & Collaborators

• Bo Wu: lead
• West China Hospital: collaborator
• Mianyang Central Hospital: collaborator
• Panzhihua Central Hospital: collaborator
• The First People's Hospital of Ziyang: collaborator
• Zigong The Fourth People's Hospital: collaborator
• Zigong No.1 Peoples Hospital: collaborator

Study Sites (1)

Bo Wu

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Bijoy Menon, MD, Phd

  University of Calgary

  PRINCIPAL INVESTIGATOR

• Bo Wu, MD, PhD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bo Wu

CONTACT

+8618980602142; dr.bowu@hotmail.com

Bijoy Menon, MD, PhD

CONTACT

+14033381198; docbijoymenon@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The neurologists and radiologists at the central imaging core laboratory who are responsible for adjudicating all imaging endpoints, including symptomatic intracerebral hemorrhage (sICH).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr.

Model Details: Different sequences of blood pressure management and intravenous thrombolysis.

Study Record Dates

• First Submitted: December 8, 2025
• First Posted: January 6, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)