Nicardipine vs. Labetalol (AISstdy)

Time to Target Blood Pressure Before Reperfusion Therapy in Acute Ischemic Stroke: Nicardipine Versus Labetalol

In this ED-based study, the investigators compared the time to reach target blood pressure (BP) between hypertensive patients with acute ischemic stroke (AIS) undergoing intravenous (IV) thrombolysis and/or mechanical thrombectomy who received IV nicardipine versus labetalol. Additionally, the investigators evaluated the rate of early neurological improvement (ENI), length of hospital stay (LOS), in-hospital mortality, and adverse event profiles between the two treatment groups.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke; Hypertensive Crisis
• Intervention / Treatment: Drug: nicardipine intravenous; Drug: labetalol intravenous

Detailed Description

Acute ischemic stroke (AIS) is a leading cause of death and long-term disability worldwide. In patients who are candidates for intravenous thrombolysis and/or mechanical thrombectomy, rapid and controlled reduction of markedly elevated blood pressure (BP) before reperfusion therapy is critical for both treatment success and safety. International guidelines recommend intravenous nicardipine and labetalol as first-line antihypertensive agents in this setting; however, existing evidence comparing these two strategies is heterogeneous, and there is ongoing uncertainty regarding which agent facilitates faster and more stable BP control in the pre-reperfusion phase.

This prospective, randomized, single-blind, single-center clinical trial evaluates two commonly used intravenous antihypertensive regimens-nicardipine versus labetalol-for BP management in hypertensive AIS patients presenting to the emergency department. Consecutive adult patients with a clinical and radiological diagnosis of AIS and severely elevated BP at presentation who were planned for reperfusion therapy were screened for eligibility.

After written informed consent was obtained, eligible patients were randomly allocated in a 1:1 ratio to receive either intravenous nicardipine or intravenous labetalol. Randomization was performed using a computer-generated sequence with allocation concealment (sequentially numbered, opaque, sealed envelopes). Treating clinicians were aware of group allocation in order to administer the assigned drug, whereas outcome assessors and the statistical team remained blinded throughout data collection and analysis.

In the nicardipine arm, patients received a continuous intravenous infusion via a peripheral venous catheter using an electronic infusion pump, with the dose titrated at short intervals according to BP response. In the labetalol arm, patients received intermittent intravenous bolus doses through a peripheral line, with repeated boluses permitted up to a predefined cumulative limit when needed. In both groups, continuous cardiac and hemodynamic monitoring was maintained during antihypertensive therapy. BP was measured at frequent, standardized intervals using automated devices and verified manually when indicated. Once the predefined BP target recommended for pre-reperfusion management in AIS was achieved, the study drug was down-titrated or withheld, and patients proceeded to reperfusion therapy in accordance with current stroke guidelines and local protocols.

Time from initiation of antihypertensive treatment to achievement of target BP is the main efficacy endpoint of this trial. Secondary endpoints include additional time-based metrics related to reperfusion therapy, drug exposure parameters, the occurrence of predefined cardiovascular and hemodynamic adverse events during antihypertensive treatment, early neurological response, and in-hospital clinical course. Neurological status is assessed using the National Institutes of Health Stroke Scale (NIHSS) at baseline and during early follow-up, and standard radiological imaging is used to identify treatment-related intracranial complications. All clinically relevant data are collected prospectively using a standardized case report form and analyzed according to an intention-to-treat approach.

This study is designed to generate prospective randomized data on the comparative effectiveness and safety of nicardipine and labetalol for pre-reperfusion BP management in hyperacute AIS. By focusing on time-to-target BP and short-term clinical outcomes in a real-world emergency department setting, the trial aims to inform clinicians' choice between these two widely used antihypertensive strategies in time-critical stroke care.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Fatih
    • Istanbul, Fatih, Turkey (Türkiye), 34265
      • Haseki Training and Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Presentation to the emergency department with clinical and radiological evidence of acute ischemic stroke (cranial CT with or without CT angiography, or diffusion-weighted MRI)
• Initial systolic blood pressure (SBP) ≥ 185 mmHg and/or diastolic blood pressure (DBP) ≥ 110 mmHg

Exclusion Criteria:

• Age < 18 years
• Intracranial hemorrhage, subarachnoid hemorrhage, or other non-stroke structural pathology on initial neuroimaging
• Stroke mimics (e.g., hypoglycemia, postictal paresis)
• Absolute contraindication to reperfusion therapy at presentation such that pre-procedural blood pressure control is not planned as part of clinical management
• Achievement of target blood pressure with prior antihypertensive treatment or receipt of other intravenous antihypertensive agents before randomization
• Hemodynamic instability or respiratory failure requiring emergency intubation and advanced life support
• Contraindications to labetalol or nicardipine (e.g., severe bronchospastic disease, advanced atrioventricular block, or critical aortic stenosis)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nicardipine group; The nicardipine group received an IV infusion of nicardipine.	Drug: nicardipine intravenous; In the nicardipine group, an 18-gauge peripheral IV catheter was preferably placed in the antecubital fossa. Continuous infusion was initiated at a starting dose of 5 mg/hour and titrated upward by 1 mg/hour every 5 minutes according to the BP response. Administration was performed using an electronic infusion pump.
Active Comparator: Labetalol group; The labetalol group received an IV bolus of labetalol.	Drug: labetalol intravenous; In the labetalol group, an 18-gauge peripheral IV catheter was preferably placed in the antecubital fossa. An initial 20 mg dose of labetalol was administered as an IV bolus. If needed, additional 20 mg boluses were given every 5 minutes, not exceeding a cumulative dose of 300 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to reach target blood pressure	The investigators assessed the time from the initiation of antihypertensive drug to the first confirmation of target BP (SBP ≤185 mmHg and DBP ≤110 mmHg).	at 15 minutes after the drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients achieving target BP	The investigators assessed the proportion of patients achieving target BP within the first 15 minutes.	at 15 minutes after the drug administration.
Door-to-needle time	The investigators assessed the door-to-needle time in patients with acute ischemic stroke.	From emergency department admission to initiation of intravenous thrombolytic therapy, assessed up to 24 hours after emergency department arrival.
The frequency and types of adverse events	The investigators assessed the frequency and types of adverse events in acute ischemic stroke patients undergoing IV thrombolysis and/or mechanical thrombectomy who received IV nicardipine versus labetalol	from emergency room admission to the 24 hours.

Collaborators and Investigators

• Sponsor: Haseki Training and Research Hospital
• Investigators: Principal Investigator: Adem Az, Assoc. Prof., Haseki Training and Research Hospital

Publications and helpful links

General Publications

• Guo QH, Liu CH, Wang JG. Blood Pressure Goals in Acute Stroke. Am J Hypertens. 2022 Jun 16;35(6):483-499. doi: 10.1093/ajh/hpac039.
• Huang A, Parker D Jr, Wein R. Comparison of nicardipine versus labetalol for time to alteplase administration in acute ischemic stroke. Front Neurol. 2025 Jul 2;16:1573352. doi: 10.3389/fneur.2025.1573352. eCollection 2025.
• Hao F, Yin S, Tang L, Zhang X, Zhang S. Nicardipine versus Labetalol for Hypertension during Acute Stroke: A Systematic Review and Meta-Analysis. Neurol India. 2022 Sep-Oct;70(5):1793-1799. doi: 10.4103/0028-3886.359214.
• Ortega-Gutierrez S, Thomas J, Reccius A, Agarwal S, Lantigua H, Li M, Carpenter AM, Mayer SA, Schmidt JM, Lee K, Claassen J, Badjatia N, Lesch C. Effectiveness and safety of nicardipine and labetalol infusion for blood pressure management in patients with intracerebral and subarachnoid hemorrhage. Neurocrit Care. 2013 Feb;18(1):13-9. doi: 10.1007/s12028-012-9782-1.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2025
• Primary Completion (Actual): July 1, 2025
• Study Completion (Actual): August 1, 2025

Study Registration Dates

• First Submitted: November 22, 2025
• First Submitted That Met QC Criteria: December 2, 2025
• First Posted (Actual): December 11, 2025

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Labetalol; Nicardipine; Acute ischemic stroke; door-to-needle time; time to achievement of target blood pressure; early neurological improvement
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Hypertension; Ischemic Stroke; Hypertensive Crisis
• Other Study ID Numbers: 01-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Stored in non-publicly available Available on request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes