Early Initiated Ambulance-delivered Levetiracetam and Headposition in Hyper-acute Stroke Trial (EAST)

An Investigator Initiated and Conducted, Prospective, Multicentre, Randomised Outcome-blinded Study of Pre-hospital Initiated Levetiracetam and Headposition in Patients With Presumed Acute Stroke

This is an investigator initiated and conducted, multicentre, ambulance-delivered, prospective, randomised, open-label, blinded outcome (PROBE) study. EAST aims to evaluate the effects of pre-hospital levetiracetam and different head positions initiated in ambulance settings on the functional outcome of participants assessed at 90 days.

Study Overview

• Status: Recruiting
• Conditions: Suspected Stroke
• Intervention / Treatment: Drug: Levetiracetam; Other: Guide-recommended management; Other: The lying flat (0°) head position; Other: The sitting-up (≥30°) head position

Detailed Description

EAST is a multicenter, ambulance-delivered, prospective, randomized controlled, open label blinded outcome assessment (PROBE) study to be conducted through a regional-cluster hospital network of investigators. A total of 2323 patients with suspected acute stroke will be recruited from approximately 50 hospitals in China. Potentially eligible patients will be recruited into the study by either of two mechanisms: (1) waver of consent to the intervention, and consent to follow-up obtained in hospital; or (ii) consent to the intervention through a brief written consent which is combined with a usual care consent form delivered in hospital for follow-up (if a waver of consent is not approved by the ethics committee). All patients will enter Part A and Part B at the same time, randomised allocation of intervention will be done in a 1:1 ratio in each part, using a central, automated, mobile phone Wechat mini program-based electronic randomization software according to minimization method stratified by ambulance systems, age (≥65 vs <65) and FAST(>2 vs =2). The intervention of Part A is to commence IV levetiracetam(LEV) 500mg as a single bolus in the ambulance and then to continue as LEV 500mg Bid orally after hospital admission for 14 days(at least 7 days if discharged or death early), compared to avoid prophylactic use of antiseizure drugs. Part B is to lie flat or sit up in the ambulance as soon as possible until hospital arrival. Ambulance staff will be well trained across the whole study to master mobile randomisation and simple key data collection. All information in ambulance, including basic demographics, randomised allocation, BP measurement and treatment details, will be collected through mobile phone based electronic database system connected with investigator clinicians in hospitals. Other relevant documents such as consent paper, BP chart will be handed over to hospital investigators. Endpoint assessment will be blinded to treatment allocation.

• Study Type: Interventional
• Enrollment (Estimated): 2423
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Gang Li, PhD, MD; Phone Number: 86 13621691786; Email: ligang@tongji.edu.cn
• Study Contact Backup: Name: Chen Chen, PhD, MD; Email: 15921119641@163.com

Study Locations

• China
  • Anhui
    • Suzhou, Anhui, China, 234399
      • Recruiting
      • Si County People's Hospital
      • Contact: Lei Shi; Phone Number: 86 18755733255; Email: 275386217@qq.com
  • Shanghai
    • Shanghai, Shanghai, China, 200123
      • Recruiting
      • Shanghai East Hospital
      • Contact: Chen Chen, MD PhD; Phone Number: 86 15921119641; Email: 15921119641@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults (age ≥18 years);
• Acute condition that is presumed due to acute stroke, defined on the FAST (Face, Arm, Speech, Time) screen (score ≥2 with an arm deficit);
• Time ≤2 hours from last seen well;
• Able to provide brief consent (if a waver of consent not approved by ethics committee).

Exclusion Criteria:

• coma (no response to painful stimulation);
• severe co-morbid disease (e.g. cancer, chronic airflow disease, severe dementia, severe heart failure, pre-existing disability [needing help with everyday activities]);
• history of epilepsy or seizure at onset;
• recent head injury;
• hypoglycaemia (glucose <2.8mmol/L);
• clear indications or contraindications (allergies) for levetiracetam;
• lactating women;
• clear indications for a particular head position or situations where either head position cannot be maintained (such as severe vomiting and inability to lie down, severe obesity with fatigue and difficulty sitting up, etc.).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levetiracetam; Prophylactic use of LEV in the ambulance	Drug: Levetiracetam; Intervention group - to commence IV levetiracetam 500mg as a single bolus in the ambulance, and then to continue as levetiracetam 500mg bid orally after admission to hospital in those with confirmed acute stroke for the next 14 days (at least 7 days if either dead or discharged from hospital if earlier). They will also receive standard management of acute stroke, whether the final diagnosis is ischaemic or ICH
Active Comparator: Guide-recommended management	Other: Guide-recommended management; To receive stroke management according to standard local guidelines, but to avoid prophylactic use of an anti-seizure drug.
Experimental: Lie flat	Other: The lying flat (0°) head position; Lie flat (0°) - in the ambulance as soon as possible until arrival at hospital.
Active Comparator: Sit up	Other: The sitting-up (≥30°) head position; Sit up(30-60°) - in the ambulance as soon as possible until arrival at hospital.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Functional shift (improvement) in 7-level mRS scores	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
neurological severity on the National Institute of Health stroke scale (NIHSS)	0-42, higher scores indicates worse severity	24 hours from randomization
neurological severity on the National Institute of Health stroke scale (NIHSS)	0-42, higher scores indicates worse severity	7 days
health related quality of life on the EQ-5D-5L		90 days
severe disability (mRS 3-5)		90 days
death and/or severe disability (mRS 3-6)		90 days
utility-weighted-mRS (UW-mRS)		90 days
proportion of hospital discharge at Day 7		7 days
living circumstances questions	living at home [the individual's own or that of a family member] or living at an institution(hospital, care facility, or other)	90 days
any seizures during follow-up	assessed by 6 screening questions modified from the Canadian Longitudinal Study on Aging-Epilepsy Algorithm (CLSA-EA)	90 days, 6 months, 12 months
haematoma volume	in patients with final diagnosis of ICH	at hospital admission and 24 hours
Hematoma expansion	in patients with final diagnosis of ICH	24 hours

Collaborators and Investigators

• Sponsor: Shanghai East Hospital
• Investigators: Principal Investigator: Gang Li, PhD, MD, Tongji University, School of Medicine, Shanghai East Hospital; Principal Investigator: Craig Anderson, MD, PhD, Fudan University; Principal Investigator: Lili Song, PhD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: January 2, 2025
• First Submitted That Met QC Criteria: January 13, 2025
• First Posted (Actual): January 14, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: intervention; Ambulance; Acute stroke; Levetiracetam; Head position
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: 2024-228

Drug and device information, study documents

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